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Transsphenoidal Surgery, by Drs. Laws and Lanzino, captures all of today's clinical knowledge on the multidisciplinary management of pituitary tumors, with a focus on surgical techniques. Acclaimed international experts bring you detailed guidance on natural history, radiologic and clinical aspects, surgical indications, and resection techniques. What’s more, case presentations and clinical photographs help you reduce the risk of error and advance your own surgical skills.

  • Refine your skills through discissions of intraoperative imaging, new techniques in transsphenoidal surgery, new microsurgical procedures, radiosurgical techniques, and more.
  • Get balanced and comprehensive perspectives on pituitary surgery from well-recognized international, multidisciplinary contributors.
  • Make better-informed decisions with case presentations, drawn from Dr. Laws's 40 plus years as a leader in pituitary surgery, that include a summary of the clinical history, preoperative radiographs, and postoperative clinical information and radiographs.
  • Tap into exceptional visual guidance and reduce the risk of error through abundant clinical photographs and line drawings.
  • Find the information you need quickly via a consistent chapter-to-chapter organization.



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Date de parution 23 août 2010
Nombre de lectures 0
EAN13 9781455700011
Langue English
Poids de l'ouvrage 2 Mo

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Transsphenoidal Surgery

Edward R. Laws, MD, FACS
Professor, Department of Neurosurgery, Harvard University
Director, Pituitary/Neuroendocrine Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachussetts

Giuseppe Lanzino, MD
Professor of Neurosurgery, Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota
Front matter
Transsphenoidal Surgery

Transsphenoidal Surgery
Edward R. Laws, MD, FACS , Professor, Department of Neurosurgery, Harvard University; Director, Pituitary/Neuroendocrine Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachussetts
Giuseppe Lanzino, MD , Professor of Neurosurgery, Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota

1600 John F. Kennedy Blvd.
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Philadelphia, PA 19103-2899
Transsphenoidal Surgery
Copyright © 2010 by Saunders, an imprint of Elsevier Inc .
All rights reserved . No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher.
Permissions may be sought directly from Elsevier’s Health Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215 239 3804, fax: (+1) 215 239 3805, e-mail: . You may also complete your request on-line via the Elsevier homepage ( ), by selecting ‘Customer Support’ and then ‘Obtaining Permissions’.

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out or related to any use of the material contained in this book.
The Publisher
Library of Congress Cataloging-in-Publication Data
Transsphenoidal surgery / [edited by] Edward R. Laws, Giuseppe Lanzino. – 1st ed.
p. ; cm.
Includes bibliographical references.
ISBN 978-1-4160-0292-5
1. Pituitary gland–Tumors–Surgery. 2. Sphenoid sinus–Surgery. I. Laws, Edward R. II. Lanzino, Giuseppe.
[DNLM: 1. Pituitary Neoplasms–surgery. 2. Endocrine Surgical Procedures–instrumentation. 3. Sphenoid Sinus–surgery. WK 585 T772 2010]
RD599.5.P58T73 2010
Acquisitions Editor : Adrianne Brigido
Developmental Editor : Taylor Ball
Publishing Services Manager : Hemamalini Rajendrababu
Project Manager : Jagannathan Varadarajan
Design Direction : Ellen Zanolle
Printed in Canada
Last digit is the print number: 9 8 7 6 5 4 3 2 1

Edward Laws, Giuseppe Lanzino
This book, which reviews the current state of transsphenoidal surgery, is dedicated to those individuals who had the courage to remain true to what had become an unpopular surgical concept, and to revive what has ultimately become one of the major advances of 21 st century neurosurgery. After performing some 440 transsphenoidal operations for pituitary lesions, Harvey Cushing abandoned the procedure in favor of craniotomy towards the end of his surgical career, and most of the rest of the neurosurgical world followed suit.
In Europe, Oskar Hirsch in Vienna continued enthusiastically with his endonasal transsphenoidal approach and ultimately brought it to the United States. In the British Isles, Norman Dott, after a year with Cushing in 1925, became an exponent of the sublabial transssphenoidal approach, and taught it to Gerard Guiot of France. Guiot trained Jules Hardy of Montreal Canada, and with the concepts of excellent lighted transsphenoidal retractors, the operating microscope, intraoperative fluoroscopy, and the idea of selective removal of microadenomas, a new era of pituitary surgery had begun.
In the United States, early pioneers of the method included Nicholas Zervas, John Van Gilder, George Tindall, Charles Wilson, Martin Weiss, Ivan Ciric, George Udvarhelyi, Kalmon Post, and others who have inspired and influenced all of us who follow.
These individuals had the courage to learn and develop a novel technique, to work collaboratively with Otorhinolaryngologists and Endocrinologists, and to persist in publishing and presenting their work despite resistance and even ridicule from their more traditional colleagues. It is exciting to consider how the evolution of these concepts has changed much of what we do in Neurosurgery, and how much this has benefitted our patients.
We are eternally grateful as well to our wives and families who have also sustained us in this work.

Amin Amini, MD, MSc, Director of Neurosurgery, Neurosciences Center, Holy Cross Hospital, Silver Spring, Maryland

Samuel S. Becker, MD, The Rhinoplasty Center / Becker Sinus, Sewell, New Jersey

René Ludwig Bernays, MD, PD Dr. med., Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland

Paolo Cappabianca, MD, Professor and Chairman of Neurosurgery, Department of Neurological Sciences, Division of Neurosurgery, Università degli Studi di Napoli Federico II, Naples, Italy

Steven Carr, MD, Resident Physician, Department of Neurosurgery, University of Colorado Health Sciences Center, Denver, Colorado

David B. Carter, Bsc, MBChB, FCS(Neurosurgery), Part time Consultant, Department of Neurosurgery, University of Cape Town, Consultant, Vincent Pallotti Hospital, Cape Town, South Africa

Domenico Catapano, MD, Department of Neurosurgery, Casa Sollievo della Sofferenza Hospital, I.R.C.C.S., San Giovanni Rotondo (FG), Italy

Luigi Maria Cavallo, MD, PhD, Neurosurgeon, Department of Neurological Sciences, Division of Neurosurgery, Università degli Studi di Napoli Federico II, Naples, Italy

William T. Couldwell, MD, PhD, Professor and Chairman, Department of Neurosurgery, University of Utah, Salt Lake City, Utah

Matteo Gabriele De Notaris, MD, Neurosurgeon, Department of Neurological Sciences, Division of Neurosurgery, Università degli Studi di Napoli Federico II, Naples, Italy

Ian F. Dunn, MD, Instructor in Neurosurgery, Department of Neurosurgery, Harvard Medical School, Attending Neurosurgeon, Department of Neurosurgery, Brigham in Women’s Hospital, Boston, Massachussetts

Dilantha B. Ellegala, MD, Department of Neurosurgery, University of Virginia, Harvard Medical School

Uygur ER, MD, Associate Professor of Neurosurgery, Second Neurosurgery Clinic, Dişkapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey

Felice Esposito, MD, PhD, Neurosurgeon, Department of Neurological Sciences, Division of Neurosurgery, Università degli Studi di Napoli Federico II, Department of Oral and Maxillofacial Surgery, Division of Maxillofacial surgery, Università degli Studi di Napoli Federico II, Naples, Italy

Giovanni Farneti, MD, Director, Department of ENT, Budrio Hospital – Bologna North, Bologna, Italy

Giorgio Frank, MD, Director, Center of Surgery for Pituitary and Endoscopic Skull Base Surgery, Department of Neurosurgery, Bellaria Hospital, Bologna, Italy

Marco Faustini-Fustini, MD, Medical Doctor, Department of Endocrinology, Bellaria Hospital, Bologna, Italy

Atul Goel, M.Ch. Neurosurgery, Professor and Head of Department, Department of Neurosurgery, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India

Benoit J. Gosselin, MD, FRCSC, FACS, Associate Professor of Surgery, Department of Surgery (Otolaryngology), Dartmouth College, Hanover, New Hampshire, Associate Professor of Surgery (Otolaryngology), Department of Head and Neck Surgery, Division of Otolaryngology, Dartmouth-Hitchcock Medical Center, Director, Comprehensive Head and Neck Cancer Program, Norris Cotton Cancer Center, Lebanon, New Hampshire

Brian R. Griffin, MD, Radiation Oncologist, Illinois Neurological Institute, OSF Saint Francis Medical Center, Peoria, Illinois

David Kolo Hamilton, MD, Assistant Professor, Department of Neurosurgery, University of Maryland School of Medicine, Assistant Professor, Department of Neurosurgery, University of Maryland Medical Center, Baltimore, Maryland

Jules Hardy, OC, MD, Hospital Notre-DameMontreal, Canada

Jay Jagannathan, MD, Neurosurgeon, Wayne State University, Detroit, Michigan

John Anthony Jane, Jr., M.D., Associate Professor of Neurosurgery and Pediatrics, Department of Neurosurgery, University of Virginia, Charlottesville, Virginia

Jorge C. Kattah, MD, Department of Neurology, University of Illinois College of Medicine, Peoria, Illinois

Andrew H. Kaye, MD, FRACS, Head of Department and James Stewart Professor of Surgery, Department of Surgery, Royal Melbourne Hospital and Western Hospital, University of Melbourne, Melbourne, Australia

Daniel F. Kelly, MD, Director, Brain Tumor Center at Saint John’s Health Center, John Wayne Cancer Institute, Santa Monica, California

Giuseppe Lanzino, MD, Professor of Neurosurgery, Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota

Edward R. Laws, MD, FACS, Professor, Department of Neurosurgery, Harvard University, Director, Pituitary/Neuroendocrine Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, Massachussetts

James K. Liu, MD, Assistant Professor, Director, Center for Skull Base and Pituitary Surgery, Department for Neurological Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey

M. Beatriz, S. Lopes, MD, PhD, Professor of Pathology and Neurological Surgery, Department of Pathology (Neuropathology), University of Virginia School of Medicine, Director of Neuropathology, Department of Pathology, University of Virginia Health System, Charlottesville, Virginia

Nicholas F. Maartens, MB, ChB, FRACS, FRCS, FRCS(sn), Department of Surgery, University of Melbourne, DoctorDepartment of Neuro Surgery, The Royal Melbourne Hospital, Melbourne, Victoria, Australia

Jonathan M. Morris, MD, Consultant, Assistant Professor, Department of Radiology, Mayo Clinic, Rochester, Minnesota

Edward C. Nemergut, MD, Associate Professor of Anesthesiology and Neurological Surgery, Department of Anesthesiology, University of Virginia, Charlottesville, Virginia

Richard R. Orlandi, MD, FACS, Associate Professor, Otolaryngology - ENT, Head & Neck Surgery, University of Utah, Salt Lake City, Utah

Stephen S. Park, MD, Vice-Chairman and Professor, Department of Otolaryngology-Head and Neck Surgery, University of Virginia, Charlottesville, Virginia

Ernesto Pasquini, Director, Department of Endoscopic Sinus and Skull Base Surgery, Department of ENT, Sant’Orsola-Malpighi Hospital, Bologna, Italy

Nader Pouratian, MD, PhD, Assistant Professor of Neurosurgery, Department of Neurosurgery, University of California, Los Angeles, California

Albert L. Rhoton, Jr., M.D, Professor and Chairman Emeritus, Department of Neurological Surgery, University of Florida, Gainesville, Florida

Patrick Lyle Semple, FCS (SA), Mmed (UCT), Department of Neurosurgery, Groote Schuur Hospital Observatory, South Africa

Jason Sheehan, MD, PhD, Associate Professor, Department of Neurological Surgery and Radiation Oncology, University of Virginia, Charlottesville, Virginia

Nathan Simmons, MD, Department of Neurosurgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire

Vita Stagno, MD, Resident, Department of Neurological Sciences, Division of Neurosurgery, Università degli Studi di Napoli Federico II, Naples, Italy

Ladislau Steiner, MD, PhD, Professor, Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia

Mary Lee Vance, MD, Professor, Department of Medicine, University of Virginia, Charlottesville, Virginia

Martin H. Weiss, MD, Professor of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
Table of Contents
Front matter
Chapter 1: Reflections on the Evolution of Pituitary Tumor Surgery with Emphasis on the Transsphenoidal Approach
Chapter 2: History of Transsphenoidal Surgery for Pituitary Tumors
Chapter 3: Principles and Pitfalls of Anesthesia for Transsphenoidal Surgery
Chapter 4: The Perioperative Care of the Pituitary Patient
Chapter 5: The Neuro-Ophthalmology of Pituitary Tumors
Chapter 6: Rhinological Evaluation
Chapter 7: Imaging of the Sella and Parasellar Region
Chapter 8: Intraoperative Imaging: Current Trends, Technology, and Future Directions
Chapter 9: Classification, Pathobiology, Molecular Markers, and Intraoperative Pathology
Chapter 10: Surgical Anatomy of the Sellar Region
Chapter 11: Microsurgical Approaches for Transsphenoidal Surgery
Chapter 12: Endoscopic Transsphenoidal Surgery: Anatomy, Instrumentation, Techniques
Chapter 13: Endoscopic Transsphenoidal Pituitary Surgery: Results and Complications
Chapter 14: The Role of Transsphenoidal Surgery in the Management of Complex Lesions Involving the Skull Base
Chapter 15: Closure Methods
Chapter 16: Complications: Avoidance and Management
Chapter 17: Transsphenoidal Surgery for Recurrent Disease
Chapter 18: Transsphenoidal Resection of Craniopharyngiomas
Chapter 19: Transsphenoidal Surgery for Cushing’s Disease: Pitfalls, Results, and Long-Term Follow-up
Chapter 20: Transsphenoidal Surgery for Acromegaly
Chapter 21: Transsphenoidal Surgery for Prolactinomas
Chapter 22: Transsphenoidal Surgery for Nonfunctioning Adenomas
Chapter 23: Pituitary Carcinoma
Chapter 24: Pituitary Metastases
Chapter 25: Pituitary Tumors in Infancy and Childhood
Chapter 26: Anatomical Approach to Giant Pituitary Tumors
Chapter 27: Radiotherapy for Pituitary Tumors
Chapter 28: Stereotactic Radiosurgery for Pituitary Adenomas
1 Reflections on the Evolution of Pituitary Tumor Surgery with Emphasis on the Transsphenoidal Approach

Jules Hardy

All major progress in human evolution occurred in the field of instruments.
—Buckminster Fuller
Over the last 10 years, numerous articles have reviewed the historical background of the surgical treatment of pituitary tumors and confronted the challenge between the alternative of intracranial versus transsphenoidal approaches. 1, 2, 3 They deserve careful reading for the understanding of the scientific evolution of the transnasal transsphenoidal approach, which has now become the standard procedure for more than 90% of the sellar lesions. 3
This introductory chapter will be confined to pertinent comments on the transsphenoidal approach with regards to significant progress in the methodology of therapy of pituitary tumors and emphasis on the technical improvements related to concurrent instrumental developments.
In his pioneering contribution, Schloffer used an upper nasal approach on his first patient on March 16, 1907. 4 A review of the French literature reveals that on April 10, 1909, Lecène performed a supranasal transsphenoidal operation in an acromegalic patient. 5 The procedure was then modified in 1910 by Hirsch, 6 who used an inferior endonasal approach on his first live patient. The technique underwent several variants by other authors in cadaver studies to be finally adopted as a standard procedure in patients by Cushing’s, 7 Dott, 8 and Guiot, 9 who remained faithful to the sublabial rhinoseptal midline approach. The lateral endonasal approach originally used by Hirsch remained an alternative procedure eventually revived by Griffith in 1987. 10
The major drawback of the open surgical approach through the nose was that it was in the past a blind procedure in a dark cavity; this had been overcome earlier by Cushing’s by using a headlight. Later, the Norman Dott bivalve speculum contained spotlights at the tip of each valve, thus providing a retractor combined with endoscopic illumination into the sphenoid cavity.
The direct approach from the nasal cavity avoids dissecting the rhinoseptal mucosa and allows direct entrance through the ostium sphenoidale into the sphenoid sinus, but the operative field is, in no way, wider than that from the rhinoseptal approach after bilateral submucosal elevation. The important issue is not where we are coming from but what we are doing once we are in the sella turcica, and how we deal with the pituitary tumor; that is the major point.
The first endoscope for transsphenoidal approach with an external light source mounted on a rigid shaft was first used by Guiot, with an original instrument devised by Fourestier-Vulmiére. 11 In 1961, I was Dr. Guiot’s assistant when he performed the first procedure with this endoscope. Although Guiot did use the endoscope for the sellar approach in several cases, he abandoned it because of its time-consuming and cumbersome maneuvers. He then used the endoscope but only occasionally to explore the sellar cavity after removal of the tumor to seek residual tumor tissue hidden in the corner laterally or underneath the tuberculum sellae. Upon my return to Montreal in 1962, I similarly used the endoscopic approach in several cases but again only to explore the sella after tumor removal.
The argument that the endoscope provides a wide field illumination allowing a panoramic view seems somewhat overstated because it is not necessary to see the lateral aspect of the sphenoid sinus nor the carotid grooves on the sides of the sella turcica. I concur with Ed Laws’ aphorism: “ It is safe to jump into endoscopic pituitary surgery without previous experience in transsphenoidal surgery .”
There has been great controversy regarding the endoscopic approach as opposed to the open approach with the surgical microscope. 12 - 14 In my opinion, this is not a major issue. A well-known surgeon (P.B.) 15 hinted that endoscopic surgery is sometimes seen as a “marketing device to try to change traditional patterns of referral for pituitary surgery.” Advertising the preferential use of an endoscope to draw the attention of a referring physician does not guarantee the superiority of the surgical outcome on the treatment of the lesion, and a study on clinical and biological statistical results comparing the alternative methods has not yet been published. 13
I came to the same conclusion that it was not more useful than the spotlights at the tips of the Dott bivalve speculum, which I used during a few years before the introduction of the surgical microscope. 16, 17
Image intensifier fluoroscopy , also introduced by Guiot, 18 was the most important advance in the early 1960s. This contributed to a better definition of the tumor contour and a clear visualization of the instruments placed in the sella at the base of the skull during the major step of the surgical procedure. Televised fluoroscopy was the very first navigating system highly useful in the removal of macroadenomas with large suprasellar expansion. 19 The injection of air in the subarachnoid space by lumbar puncture as a way to outline the superior contour of the tumor provided clear delineation of the intracranial contour of the tumor for monitoring the placement of instruments and the protection of the supratumoral nervous structures: optic nerves, chiasm, hypothalamus, and adjacent cerebral arteries. This provided significant advancement in the transsphenoidal approach for removal of large pituitary tumors and other lesions around the sella turcica. The major indication was the symmetrical midline suprasellar expansion, which could be removed in one or two stages, depending on the consistency of the lesion. 20
In my experience, this method of navigating toward the sella with image intensifier–guided fluoroscopy is the most secure and safest procedure. It provides a real time radiologic image of the tumor and sequential modification during the progressive descent of the tumor into the sella turcica. Such dynamic imaging is not yet available by the use of magnetic resonance imaging (MRI) guided system unable to provide a real-time picture. As the suprasellar mass is moving down into the sella turcica and the magnetic resonance image remains the same on the screen, it is no longer useful as a reference and is in fact potentially dangerous for inaccurate placement of the instruments beyond the virtual image. It is also useless in the identification of bony landmarks, such as the anterior nasal spine and the vomer bone, that guide the surgeon towards the sella. Only in cases of large invasive tumors, or in repeated surgery where the bony landmarks are destroyed, does midline identification with image guidance become as useful with MRI as it is with the computed tomography–guided assisted fluoroscopy. 21 The use of an MRI system in transsphenoidal pituitary tumor surgery has therefore not yet proved to be superior to the actual standard image-intensified fluoroscopic method. If subarachnoid air injection via the lumbar route fails, the injection of soluble contrast material (omnipac-240: iohexol USP-52%) directly into the tumor with a 26-gauge needle is an alternative. The opaque perfusion of the entire tumor outlines its boundaries for placement of curettes into the tumoral cavity. Progressive excision of the opacified tumor serves as a marker for tumor removal and lasts about 10 minutes before being completely reabsorbed. Preoperative MRI identification of the residual normal gland helps the surgeon to preserve it while doing selective tumoral tissue removal. 22
The recently introduced intraoperative MRI-guided system is a promising instrument because it affords the combination of real-time image acquisition and integrated optical tracking capabilities. 23
The introduction of the surgical microscope constituted a major technical development with magnification coupled with bright illumination allowing the surgeon to distinguish clearly between normal and pathological tissues well visualized in three dimensions. 16 This concept evolved from my experience with hypophysectomies for treatment of advanced painful metastatic breast cancer, while at the same time I was exploring patients with Cushing’s disease or acromegaly with a small sella. 16, 24 Becoming familiar with the appearance and texture of the normal hypophyseal tissue, the discovery of intrapituitary microadenomas and their selective removal became possible, and eventually this knowledge was applied to the treatment of hypersecreting pituitary disorders. This discovery has revolutionized the therapeutic concepts in neuroendocrinology—patients could not be submitted to a selective adenomectomy without resulting in hormonal deficit and replacement therapy. Furthermore, preoperative deficits could be corrected with resumption of normal functions. 16 Refinements, in microscopic techniques were required to achieve selective microadenomectomy because of the small size of a lesion hidden inside the pituitary parenchyma. 17, 25
Selective extraction of a microadenoma in the lateral wing of the gland (GH and PRL) requires delicate maneuvers with blunt-ended microenucleators to avoid perforating through the lateral dura of the sella, entering into the cavernous sinus, and lacerating the carotid artery. An invading lesion is removed by aspiration and gentle scooping with a curette, which may penetrate the cavernous sinus, thus producing a flush of blood along with the tumor tissue. The proper response then should be packing and not coagulation.
Laterally located lesions may require partial wing resection to ensure complete excision of the microadenoma. Posteriorly located lesions should not be pulled out but rather aspirated to prevent tugging on the inferior hypophysial artery and its ascending branch along the pituitary stalk and the anterior hypothalamic nuclei. Disruption of this vessel may result in permanent diabetes insipidus. 26, 27 Centrally located microadenomas, most frequently found in Cushing’s disease, are easier to enucleate but they can extend posteriorly into the neural lobe, which needs to be excised to achieve complete tumor removal and therefore biological control of the disease. Adrenocorticotropic hormone microadenomas not visible on the surface of the gland can be detected by ultrasound imaging, as originally described by Oldfield. 28 During these procedures, accidental arachnoidal tearing produces a cerebrospinal fluid leak that must be repaired as described elsewhere in the book. The extended transsphenoidal approach for other lesions of the sellar and parasellar regions such as craniopharyngiomas, clivus chordomas, and meningiomas, had already been described in 1971. 17 Further developments in the “classic” transsphenoidal approach using the most recent technical modalities are discussed in the following chapters.


1. Lanzino G., Laws E.R.Jr. Key personalities in the development and popularization of the transsphenoidal approach to pituitary tumors: an historical overview. Neurosurg. Clin. N. Am. . 2003;14:1-10.
2. Liu J.K., Dak K., Weiss M.H., et al. The history and evolution of transsphenoidal surgery. J. Neurosurg. . 2001;95:1083-1096.
3. Liu J.K., Weiss M.H., Couldwell W.T. Surgical approaches to pituitary tumors. Neurosurg. Clin. N. Am. . 2003;14:93-107.
4. Schloffer H. Erfolgreiche Operation eines Hypophysentumors auf nasalem Wege. Wien. Klin. Wochenschr. . 1907;20:621-624.
5. Lecéne M.P. Intervention chirurgicale sur l’hypophyse dans un cas d’acromégalie. Presse Méd. . 1909;85:747-750.
6. Hirsch O. Endonasal method of removal of hypophyseal tumors. JAMA . 1910;55:772-774.
7. Cushing H. Surgical experiences with pituitary disorders. JAMA . 1914;63:1515-1525.
8. Dott N.M., Bailey P. A consideration of the hypophysial adenomata. Br. J. Surg. . 1925;13:314-366.
9. Guiot G., Arfel G., Brion S., et al. Adénomes hypophysaires. Paris: Masson, 1912;276.
10. Griffith H.B., Veerapen R.A. A direct transnasal approach to the sphenoid sinus. Technical note. J. Neurosurg. . 1987;66:140-142.
11. Guiot G., Rougerie J., Fourestier M., et al. Explorations endoscopiques intracranienne: une nouvelle technique endoscopique. Presse Med. . 1963;71(24):1225-1228.
12. Cappabianca P., Alfieri A., Thermes S., et al. Instruments for endoscopic endonasal transsphenoidal surgery. Neurosurgery . 1999;45:392-396.
13. Cappabianca P., de Divitiis E. Endoscopy and transsphenoidal surgery. Neurosurgery . 2004;54:1043-1050.
14. Jho H.D., Carrau R.L., Ko Y., et al. Endoscopic pituitary surgery: an early experience. Surg. Neurol. . 1997;47:213-233.
15. Black P. Endoscopy and transsphenoidal surgery [Comment]. Neurosurgery . 2004;54:1050.
16. Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin. Neurosurg. . 1969;16:185-216.
17. Hardy J. Transsphenoidal hypophysectomy. J. Neurosurg. . 1971;34:582-594.
18. Guiot G. Considerations on the surgical treatment of pituitary adenomas. In: Fahlbusch R., Werder K.V., editors. Treatment of Pituitary Adenomas. 1st European Workshop . Thieme: Stuttgart; 1978:202-218.
19. Hardy J., Wigser S.M. Transsphenoidal surgery of pituitary fossa tumors with televised radiofluoroscopic control. J. Neurosurg. . 1965;23:612-619.
20. Mohr G., Hardy J., Comtois R., et al. Surgical management of giant pituitary adenomas. CJNS . 1990;17:f62-f66.
21. Jane J.A.Jr., Thapar K., Alden T.D., et al. Fluoroscopic frameless stereotaxy for transsphenoidal surgery. Neurosurgery . 2001;48:1302-1307.
22. Sade B., Mohr G., Vézina J.L. Distortion of normal pituitary structures in sellar pathologies on MRI. Can. J. Neurol. . 2004;31:467-473.
23. Hadani M., Spiegelman R., Feldman Z., et al. Novel, compact, intraoperative magnetic resonance imaging-guided system for conventional neurosurgical operating rooms. Neurosurgery . 2001;48:807-809.
24. Hardy J. Surgery of the pituitary gland, using the transsphenoidal approach. Comparative study of 2 technical methods. Union Med. Can. . 1967;96:702-712. (Fr)
25. Hardy J. Atlas of Transsphenoidal Microsurgery in Pituitary Tumors. New York: Igaku-Shoin, 1991;74.
26. Gorczyca W., Hardy J. Arterial supply of the human anterior pituitary gland. Neurosurgery . 1987;20:369-378.
27. Leclercq T.L., Grisoli F. Arterial blood supply of the normal pituitary gland. J. Neurosurg. . 1983;58:678-681.
28. Ram Z., Shawker T.H., Bradford M.H., et al. Intraoperative ultrasound-directed resection of pituitary tumors. J Neurosurg . 1995;83:225-230.
2 History of Transsphenoidal Surgery for Pituitary Tumors

Giuseppe Lanzino, Domenico Catapano, Edward R. Laws

Like many advances in medicine, the transsphenoidal procedure as we know it today is the result of a long, relentless process. Many bold and creative pioneer surgeons have contributed and continue to contribute to its continuous refinement. In the late 1800s and early 1900s, better understanding of the pathological processes involving the pituitary gland and the introduction of diagnostic x-ray techniques by Roentgen paved the way to the first attempts to surgically resect lesions involving the sellar region.

The Origins
Sir Victor Horsley is credited to have performed the first transcranial pituitary operation in 1889. However, the limitations of this approach were immediately evident primarily because of significant frontal lobe retraction necessary to obtain adequate exposure of the sellar and parasellar structures. These pitfalls encouraged pioneer surgeons at the beginning of the twentieth century to reach the pituitary region through an extracranial route through the paranasal sinuses. In Venice, Davide Giordano had conducted a series of experiments on cadavers and had suggested a transnasal route to approach the pituitary region. 1 Inspired by these studies, Hans Schloffer removed a pituitary tumor through a lateral rhinotomy and a transmaxillary/transethmoidal approach in Innsbruck, Austria, in 1907. 2 Additional initial efforts concentrated on obtaining a short route to the pituitary region through large superficial openings to improve illumination in the depth of the surgical field 3 ( Figure 2-1 ). This quite often resulted in disfiguring scars ( Figure 2-2 ). Moreover, it was difficult to maintain a proper midline orientation in the deep, dark, and narrow surgical field.

Figure 2-1 Loewe’s approach to the sphenoid sinus and the sella: A and B, Opening of the supratentorial ethmoid sinuses. C, Orbital adipose tissue. D, Posterior wall of the hindmost ethmoid cell facing the floor of the sella. E, Cavity of the hindmost ethmoid cell. F, Lamina papyracea. G, Spheno-ethmoid recess. H, Maxillary sinus. I, Posterior end of inferior concha. K, Lower margin of piriform aperture, L, Nasal cavity. M, Aperture of sphenoid sinus. N, Anterior end of inferior concha. O, Deflected nasal septum.
(Source: Loewe L. Ueber die freilegung der sehnervenkreuzung und der hypophysis und über die beteiligung des siebbeinlabyrinthes am aufbau der supraorbitalplatte. Z Augenheilk. 1908; 19:456-464)

Figure 2-2 Disfiguring scar in a 20-year-old man 2 years after a pituitary adenoma operation using von Eiselsberg’s original technique.
(Source: von Eiselsberg A, von Frankl-Hochwart L: Operations upon the hypophysis. Ann Surg 1910; 52:1-14)
Trying to overcome some of these problems, Theodor Kocher ( Figure 2-3 ), a Swiss surgeon who won the Nobel Prize in 1909 for his work on thyroid disease, proposed an approach that encompassed submucosal dissection of the sphenoid septum. The septum was exposed through a complex external incision and dissected submucosally on both sides and the mucosa retracted with a specifically designed speculum. After the resection was completed, gauze saturated with iodine was left in the tumor bed with a string attached to it coming out of the nostril. Kocher’s innovation represented a milestone in the evolution and development of transsphenoidal surgery because it allowed the surgeon to maintain a midline orientation during the procedure and decreased the danger of infection by working through a cleaner route. Additionally, Kocher’s incision, although quite complex, represented a significant improvement over earlier cosmetically disfiguring ones.

Figure 2-3 Theodor Kocher (1841-1917).
(Source: Liebermann-Meffert D: World J Surg 2000; 24:2-9)
Kocher was a legendary figure of early twentieth century surgery and achieved worldwide fame primarily for his expertise in the surgical treatment of thyroid disorders. Harvey Cushing’s, at the suggestion of Halsted, spent some time in Kocher’s clinic during his year in Europe. He was highly impressed with Kocher’s surgical technique and his maniacal attention to careful dissection and hemostasis. Later in the year, Cushing’s (by then world renowned) commemorated Kocher on the occasion of the International Neurological Congress in Berne in 1931:

The most precious heritage of our profession lies in the noble traditions. What has been accomplished does not die, but too often, alas, the personality of those who have handed the torch from one generation to another soon fades into oblivion. So for those of you—his spiritual grandchildren—who have gathered here and to whom Kocher is little more than the name of a street which you have frequently traversed the past few days, I would like to give at least an impression of what he was in life—a slight, sparse man of personal neatness, of quick step and alert hearing, of unfailing courtesy and dignity, precise and scrupulous in all his dealings, professional, public and personal—a man to trust. 4

Oskar Hirsch and the Endonasal Transseptal Approach
The transsphenoidal procedure as we know it today evolved from the simultaneous work of Oskar Hirsch in Vienna and Harvey Cushing’s in Boston. Oskar Hirsch ( Figure 2-4 ), a young rhinologist in Vienna, proposed at a meeting of the local medical association in March 1909 that the pituitary region could be reached with a much smaller opening of the facial skeleton than the ones proposed by Schloffer, von Eiselberg, and others. Instead he proposed a much smaller opening similar to that used by his teacher Hajek for the treatment of sphenoid sinus infections. 5 Hajek himself, however, had judged this approach too difficult and dangerous. Nevertheless one year later, Hirsch performed the first operation in which the approach was made through a direct transethmoidal route without reflection of the nose. The first operation was carried out in five steps under local anesthesia spanning a period of 2 weeks. At the end, the patient’s vision improved. Hirsch soon modified this operation to a submucosal transseptal method, and on June 4, 1910, he performed his first endonasal, submucosal resection of the septum ( Figure 2-5 ). By coincidence, on the same day on the other side of the Atlantic Ocean, Cushing’s performed his first sublabial transseptal excision of a pituitary tumor. Eventually Hirsch mastered the operation so that it could be conducted in one single step. In Hirsch’s operation, the mucosal flaps were retracted laterally and exposure was maintained by the use of an instrument very familiar to a rhinologist: a nasal speculum (see Figure 2-5 ). Hirsch corresponded with Cushing’s after these early attempts to inquire about Cushing’s own experience with the operation. 6 Hirsch demonstrated the procedure in Vienna for Cushing’s in 1911. 7

Figure 2-4 Oskar Hirsch (1877-1965).
(Source: Hamlin H: Surg Neurol 1985; 16:391-393)

Figure 2-5 Hirsch endonasal submucosal transseptal approach to the sella turcica. A speculum is used to retract the mucosal flaps laterally and to maintain exposure.
(Source: Hardy J: J Neurosug 1971; 34:582-594)
After resection of the tumor, Hirsch added local radiation using a rudimentary apparatus secured to the superior teeth and left in situ for some time. Between 1910 and 1956, 413 patients were treated by Hirsch with a combination of surgical resection followed by local radiotherapy. 8 Hirsch operated with the patient
… seated with the head fixed, while awake and under the influence of no other medication. The nasopharyngeal surface was cocainized and the mucosa infiltrated by a local anesthetic. Hirsch would sit opposite with instruments at hand. Illumination was provided by a reflective-mirrored light, and suction was applied by a foot-pedal rig operated by a faithful dwarf (an ex-patient named Shostel). 7
Because of the political turmoil in Europe in the late 1930s, Hirsch was forced to leave Vienna and, in 1938, moved to Boston where he continued his work. He was uncompromising in defending the transsphenoidal procedure at a time when every other surgeon in the United States had abandoned it. While in Boston, Hirsch continued to work with a neurosurgeon, Hannibal Hamlin, and together they performed over 500 cases of pituitary surgery. Hamlin continued to use the procedure, defending its advantages in properly selected patients. 9 The challenges faced by these early pioneers are evidenced by the words of Dr. Richard Rovit, who was a young trainee at the Massachusetts General Hospital at the time when Hamlin and Hirsch were still performing their transsphenoidal procedures:

One incident involving Dr. Hirsch stands out in my memory. A 61-year-old woman with hypopituitarism had been followed for years by the staff of endocrine services at MGH. Skull x-ray films revealed progressive ballooning of the sella turcica … she had received two courses of radiation therapy. Despite this therapy, and while being maintained on thyroid medication and cortisone, the patient experienced bitemporal hemianopsia with decreased vision in both eyes, especially the left, and a left sixth nerve paralysis. Because of progressive visual impairment, Dr. Hirsch, assisted by Hannibal Hamlin, performed a transsphenoidal operation in October 1957.
The transsphenoidal procedures were performed not in the usual operating rooms but in the neurosurgical x-ray suite. The patient was seated in a chair, fully awake, with the head firmly secured. The nasopharynx was treated with cocaine, and the mucosa was infiltrated with a local anesthetic. Dr. Hirsch sat facing the patient while Dr. Hamlin stood behind the patient’s head wearing a headlight, which was projected into an ear-nose-throat mirror worn by Dr. Hirsch and then reflected into the patient’s nasopharynx. Because no one except Dr. Hirsch could see anything, the resident assigned to the case, presumably to bear witness, would sit in the corner of the room and try to stay awake.
In this particular case, Dr. Hirsch entered the sella floor without incident. But after a few manipulations, a sudden torrent of bright red blood gushed from the nose under arterial pressure, splashing everything in the vicinity. After the usual instantaneous profanities, Dr. Hirsch calmly said, ‘This is not the time to curse. This is the time to pray.’ With that admonition and the loss of several hundred additional milliliters of blood, he skillfully packed the nose and the bleeding was controlled. No further bleeding was encountered when the packing was removed several days later. Subsequent angiography revealed a large internal carotid artery aneurysm that filled the sella. The patient initially did well but eventually died after an intracranial procedure with carotid ligation under hypothermia. 10, 11

Harvey Cushing’s and the Sublabial Transsphenoidal Approach
Contemporarily to Hirsch, Harvey Cushing’s proposed a sublabial transseptal transsphenoidal approach to the pituitary region ( Figure 2-6 ). In his description of the procedure, Cushing’s acknowledged the contributions of several pioneers:

The procedure which I have come to employ is merely a composite of such modifications of the Schloffer operation, suggested by Kanavel, Halsted, Hirsch, and others, as are adapted to my own requirements. It therefore makes no claim for originality. The operation combines all of the advantages of the endonasal procedure of Hirsch, and for one who does not possess the practiced hand of the rhinologist it has the further advantage of affording almost double room that an operation through one nostril permits. 12

Figure 2-6 Cushing’s sublabial approach. Sagittal reconstruction after substitution of the two lateral retractors with a self-retaining bivalve speculum through which further steps are conducted.
(Source: Cushing H: Disorders of the pituitary gland. Retrospective and prophetic. JAMA 1921; 76:1721-1726)
At the beginning of his experience, Cushing’s preferred the transsphenoidal approach to the transcranial one:

It is fair to say that this experience while discouraging is slight, and I shall further pursue this matter as favorable circumstances arise, but certainly the cases for which a frontal operation is indicated cannot compare, either in number or on the ground of risk or of promised improvement, with those to be discussed under the following heading in which a transsphenoidal operation is suitable. 12
Cushing’s used almost exclusively the transsphenoidal procedure for pituitary lesions, however, in later years he found himself using the transcranial approach more and more often and in 1921 he wrote:

Surgeons have assailed it (the pituitary) from below through the nasal cavities, and from above through the skull elevating the frontal lobe either from the front or the side. It is certain that no method is applicable for all conditions of pituitary tumor and that for some no satisfactory procedure has been devised. Speaking for myself, I find that I am conducting proportionately fewer rather than more transsphenoidal operations, though in favorable cases with a large ballooned sella I believe the latter to be the simplest and easiest method, the one most free from risk and most certain to lead to a rapid restoration of vision. However, in increasing numbers, both in children and adults, suprasellar tumors giving secondary hyperphyseal symptoms are being recognized, and if the sella is not enlarged an approach from above is necessitated. 13
In 1929, he abandoned the transsphenoidal procedure in favor of the transcranial approach. Cushing’s rejection of the transsphenoidal procedure in favor of the transcranial route is dramaticized by the fact that the famous 2000th operation for a brain tumor was a transfrontal removal of a pituitary tumor. 14 Even though the true reasons for these dramatic changes are not quite clear, this choice was probably dictated by multiple considerations. Safety of transcranial operations had greatly improved thanks primarily to Cushing’s efforts. There was also a perception that the outcome of visual field improvement was better after transcranial removal than transsphenoidal resection. Lastly, diagnostic surprises such as aneurysms and lesions other than adenomas were not uncommon and much more difficult to recognize and deal with through the narrow exposure provided by the transsphenoidal procedure. 15 Because of Cushing’s leadership, most surgeons followed and the transsphenoidal procedure was virtually completely abandoned (with the exception of Hirsch, Hamlin, and a few others) in favor of the transcranial approach.

Norman Dott’s and Gerard Guiot’s Contribution to Transsphenoidal Surgery
The resurgence of the transsphenoidal procedure which took place in the late 1960s—40 years after Cushing’s had abandoned it in favor of the transcranial route—is indirectly related to Norman Dott. Dott, a neurosurgeon at the Royal Infirmary of Edinburgh, was awarded a Rockefeller fellowship and spent a full year on Cushing’s service from November 1923 to June 1924 ( Figure 2-7 ). In 1925, Dott summarized with Percival Bailey Cushing’s experience with the transsphenoidal approach. In this dissertation, Dott defended the benefits of the transsphenoidal route expressing those that were (at least at that time) the views of the “Chief”: 16

Figure 2-7 Photograph showing Cushing’s team during Dott’s stay in Boston. Dott is standing in the back row (last person on the right). Cushing is seated in the center of the front row.
(Source: Rush C, Shaw JF: With sharp compassion. Normann Dott: Freeman Surgeon of Edinburgh. Aberdeen University Press, Aberdeen, UK, 1990, p. 130.)
In the introduction to this manuscript, Cushing’s wrote:

It is highly profitable at times for a chief of service to play the part of bystander and to see what interpretations younger and fresher minds may put upon matters in which he perhaps has somewhat fixed ideas. 17
Dott (who is also credited to have been the first neurosurgeon to attack directly a middle cerebral artery aneurysm wrapped in a nursing home in 1930), 18 continued to use the transsphenoidal procedure once back in Edinburgh even at the time when Cushing’s had completely abandoned it in favor of the transcranial procedure. Dott was also an accomplished pediatric surgeon with an active interest in the correction of congenital anomalies such as cleft palate and one wonders how much this expertise contributed to his feeling comfortable in a deep dark field at a time when most neurosurgeons were abandoning the procedure. 18 The practical difficulties encountered while performing transsphenoidal procedures are eloquently summarized in this recount of Dott’s operation by Dr. J.F. Shaw:

Now watch Dott carrying out a typical pituitary operation. The patient, lying supine, is covered overall by surgical drapes: only the nose and the mouth are exposed. Dott leans over this area with a headlight on and every now and then adjusts the position of the long malleable light, held by the assistant. Anxiety lies in the narrowly exposed eye of his assistant who is responsible for maintaining the correct position of this light but can only fleetingly see the deep operation site as he peers first one way then another around Dott’s neck and hands. Sister too looks anxious, especially when she sees the light starts to flicker and go out, which, test it as you may before the operation, seems unfailingly to occur at least once during the crucial period.
How Dott would have appreciated the convenience of transaxial illumination of the operating microscope which was denied to him by a matter of years. Sister can see even less of the operating field than the assistant and the confident way she slaps the instruments into Dott’s outstretched hand comes only from years of experience and the ability to deduce the stage of the operation from sound and hand movements. She too, in company with the small group of hopeful postgraduate students hovering behind the assistant, seeing little but hanging eagerly on any word or gesture, would have appreciated the modern microscope, with its television facility; all would have been shown so clearly, on a nearby screen. So approximately ninety minutes pass to the noise of the sucker, or of instruments against bone, the silence of soft tissue, the occasional, sometimes testy, interjection. Then Dott packs the nose and strips off his gloves. His assistants have been privileged by an occasional fleeting glance of the vital areas. 18
Dott tried to overcome some of the pitfalls of the transsphenoidal procedure. For example, to obviate the lack of illumination in a deep, narrow field he devised a modified speculum with lights attached to it.
Gerard Guiot, one of the unsung heroes of modern neurosurgery, visited Norman Dott in 1956 and observed his transsphenoidal operation. Guiot later recalled:

During those two weeks I saw Dr. Dott operating on two pituitary tumors by transsphenoidal route. And I remember Dr. Dott telling me the day after: ‘look at the postoperative campimetry! The patient is already improved’… he showed me his statistics: no mortality for his last 80 cases…I was convinced. Back to Paris I had to buy the Dott instruments and I began to operate the year after. At the Foch Hospital I began to use the image intensifier…I thought it was possible to have radioscopic control during the operation. So I changed the position of the patient…N Dott never published his results! I think it was by respect for the memory of his master, H Cushing’s who had abandoned this route… My staying at the Royal Infirmary of Edinburgh in 1956 was the first of the stayings during which I received for ever an extraordinary lesson of surgical meticularity. 14
Back in France, Guiot started using the transsphenoidal procedure. Because of the lack of instruments appositely designed for the procedure, Guiot had to design all the instruments. He was very creative in this respect, and had a relative who was retired and very skilled and who prepared under Guiot’s guidance some of the instruments in his own garage (Derome, personal communication, 2001). Guiot introduced intraoperative radiologic control. This innovation was a gradual one. 19 At the beginning a portable fluoroscopy with a screen was not available; instead Guiot and his group at Foch Hospital used a complicated x-ray apparatus hung from the operating room ceiling. One of the assistants would look directly into the apparatus with binoculars and guide the instruments of the operator during the approach and the opening of the sellar floor (Derome, personal communication, 2001). Since Guiot’s introduction of the transsphenoidal procedure until his successor Patrick Derome’s retirement from the chair of the department in the late 1990s, the “Foch” group had collected approximately 5500 cases of transsphenoidal surgery.
A versatile surgeon, Guiot had a clinical and academic interest in functional neurosurgery. Jules Hardy spent a year at the Foch Hospital with Guiot to learn functional and stereotactic procedures ( Figure 2-8 ). While in Paris, he also observed numerous transsphenoidal procedures, which he started performing once back in Montreal. The rest is recent history as outlined in the following chapters.

Figure 2-8 Jules Hardy ( right ) performing a functional procedure under the close scrutiny of Gerard Guiot ( left ) during his stay in Paris.
(Courtesy Jules Hardy, MD)


1. Giordano D. Compendio di chirurgia operatoria. Torino: Unione Tipografico-Editrice Torinese, 1897;101-104.
2. Schloffer H. Erfolgreiche Operation eines Hypophysentumors auf nasalem Wege. Wien. Klin. Wochenschr. . 1907;20:621-624.
3. Landolt A.M. History of pituitary surgery: transsphenoidal approach. In: Landolt A.M., Vance M.L., Reilly P.L., editors. Pituitary Adenomas . St Louis: Churchill Livingstone; 1996:307-314.
4. Fulton J.F. Harvey Cushing. A bibliography. Springfield, Ill: C. Thomas, 1946.
5. Hirsch O. Eine neue Methode der endonasalen Operation von Hypophysentumoren. Wien. Med. Wochenschr. . 1909;59:636-1367.
6. Lanzino G., Laws E.R.Jr. Pioneers in the development of transsphenoidal surgery: Theodor Kocher, Oskar Hirsch, and Norman Dott. J. Neurosurg. . 2001;95:1097-1103.
7. Hamlin H. Oskar Hirsch. Surg. Neurol. . 1981;16:391-393.
8. Hirsch O. Hypophysentumoren—ein Grenzgebiet. Acta Neurochir. . 1958;5:1-10.
9. Hamlin H. The case of transsphenoidal approach to hypophysial tumors. J. Neurosurg. . 1962;19:1000-1003.
10. White J.C., Ballantine H.T.Jr. Intrasellar aneurysms simulating hypophyseal tumors. J. Neurosurg. . 1961;18:34-50.
11. Rovit R.L. Transsphenoidal surgery. (letter). J. Neurosurg., 96, 2002: 1159-1160
12. Cushing H. The Weir Mitchell lecture. Surgical experiences with pituitary disorders. JAMA . 1914;63:1515-1525.
13. Cushing H. Disorders of the pituitary gland. Retrospective and prophetic. JAMA . 1921;76:1721-1726.
14. Rosegay H. Cushing’s legacy to transsphenoidal surgery. J. Neurosurg. . 1981;54:448-454.
15. Lanzino G., Laws E.R., Feiz-Erfan I., et al. Transsphenoidal approach to lesions of the sella turcica: historical overview. Barrow Q . 2002;18:4-8.
16. Dott N.M., Bailey P. A consideration of the hypophyseal adenomata. Br. J. Surg. . 1925;13:314-366.
17. Cushing H. Prefatory note. Br. J. Surg. . 1925;13:314-316.
18. Rush C., Shaw J.F. With sharp compassion. Norman Dott: Freeman surgeon of Edinburgh. Edinburgh: Aberdeen University Press, 1990.
19. Lanzino G., Laws E.R.Jr. Key personalities in the development and popularization of the transsphenoidal approach to pituitary tumors: an historical overview. Neurosurg. Clin. N. Am. . 2003;14:1-10.
3 Principles and Pitfalls of Anesthesia for Transsphenoidal Surgery

Edward C. Nemergut

Patients having transsphenoidal surgery offer many unique challenges to the anesthesiologist. Because of the prominent role of the pituitary gland in the endocrine system, patients require meticulous preoperative assessment, intraoperative management, and postoperative care. The successful anesthetic management of patients undergoing transsphenoidal surgery requires a working understanding of the relevant pathophysiology and the possible implications of anesthesia and surgery.

Pituitary adenomas are normally found in adults with a peak incidence during the fourth to the sixth decade of life. 1 Patients with tumors of the pituitary gland may be commonly encountered and represent approximately 10% of diagnosed brain neoplasms. Approximately 75% of pituitary tumors are “functioning” and produce a single, predominant hormone. Although the overall incidence of pituitary tumors remains relatively low, autopsy series suggest that as many as 20% of people may have a pituitary tumor on postmortem examination. 2, 3 Consequently, it appears that the overwhelming majority of pituitary tumors are asymptomatic. Pituitary adenomas are often classified based upon their size at the time of discovery. Tumors larger than 10 mm in any dimension are classified as macroadenomas , whereas tumors smaller than 10 mm are classified as microadenomas .
In general, pituitary tumors can present in three discrete ways: (1) hormonal hypersecretion; (2) local mass effects; or (3) tumors may be discovered incidentally during cranial imaging for an unrelated condition. Functioning tumors are usually composed of a single cell type and produce a single, predominant hormone. Patients having functioning tumors and the signs and symptoms of hormone excess will be discussed in detail later.
Local mass effect upon adjacent structures by the expanding intrasellar mass may be encountered in any type of pituitary tumor. Indeed, the most common complaints of patients with a sellar mass are headache and, in patients with a macroadenoma, visual loss. 4 Visual loss results from compression of the optic chiasm and is classically temporal or bitemporal hemianopsia. Intrasellar growth can cause anterior pituitary compression and dysfunction, resulting in hypopituitarism. Hypopituitarism results from the compression of normal gland by the expanding intrasellar mass. As patients with “nonfunctioning” tumors do not, by definition, have hormone excess, their presenting symptoms are all related to local mass effects.

General Preoperative Concerns
As in the case of any expanding intracranial mass, patients can experience raised intracranial pressure (ICP). Pituitary tumors may increase ICP in two different ways: (1) directly, by mass expansion in the sella with subsequent edema; or (2) indirectly, by obstruction of the third ventricle. Despite the fact that most patients will have a headache, elevated ICP is quite rare. Should ICP be increased, it is critical to avoid any maneuver that might further increase ICP and result in brainstem herniation or impairment of cerebral perfusion. The preoperative use of mannitol to decrease ICP should be considered.
All patients require thorough preoperative laboratory evaluation before surgery. Evaluation should include a complete blood count to assess the presence of anemia or other hematologic abnormalities. Men having pituitary tumors and low testosterone have an increased incidence of preoperative anemia. 5 Coagulation studies including prothrombin time (PT) are not mandatory unless the patient has history of, or risk factors for, bleeding. A blood urea nitrogen (BUN) and creatinine are useful as indicators of renal function; however, they may not be necessary in otherwise healthy individuals. A metabolic panel to evaluate possible hyponatremia, hypercalcemia, hyperglycemia, and other metabolic abnormalities is indicated. Hypernatremia may indicate posterior pituitary dysfunction and the presence of diabetes insipidus (DI). Patients with Cushing’s disease may have a hypokalemic alkalosis. The endocrine evaluation of each patient should include a thyroid panel (thyroxine, thyroid stimulating hormone [TSH]), and serum levels of cortisol. Many patients will have hypothyroidism or low cortisol secondary to hypopituitarism and mass effect of the tumor. Overtly hypothyroid patients should have thyroid function normalized before surgery. Patients with adrenal suppression and low cortisol will require supplementation. Many patients will have a defective stress response to surgery and require perioperative “stress dose” steroids. If patients are not surgical candidates or require further evaluation before definitive tumor resection, medical therapy is available to abrogate some of the systemic effects of functional adenomas. Additionally, medical therapy may represent the first line treatment in some instances (e.g., prolactinomas).
Review of preoperative computed tomography (CT), magnetic resonance imaging (MRI), and occasionally cerebral angiograms are particularly valuable when a patient’s clinical presentation includes facial pain, facial numbness, visual field disturbances, or other cranial nerve palsies. Often, these symptoms can suggest lateral extension of the tumor into the cavernous sinus. If such is the case, the possibility of hemorrhage from damage to the cavernous sinus or the internal carotid should be anticipated. Large bore intravenous access should be secured and blood products should be readily available before surgical incision.

Preoperative Concerns Related to Endocrine Disease
Optimal anesthetic management necessitates a thorough understanding of the pathophysiology associated with neuroendocrine disease. Advances in laboratory evaluation and radio imaging have allowed for earlier diagnosis and visualization of tumors; however, it is important to note that most tumors have an insidious, nonspecific onset. Patients may not seek medical care for years, often not until they have developed severe, multiorgan disease. Special attention in this discussion will be given to acromegaly and Cushing’s disease because they present a number of unique challenges to the anesthesiologist ( Table 3-1 ).
Table 3-1 Special Considerations in Patients with Acromegaly or Cushing’s Disease   Acromegaly Cushing’s Disease Airway
Airway obstruction
Laryngeal stenosis
Potential difficult intubation Airway obstruction Cardiovascular
Raynaud phenomenon
Valve disease
Sensitivity to catecholamines
Left ventricular hypertrophy
Intraventricular septal hypertrophy Respiratory
Obstructive sleep apnea
Pneumomegaly Obstructive sleep apnea Metabolic Glucose intolerance
Diabetes mellitus
Hypokalemic alkalosis Renal Chronic volume expansion Nephrolithiasis Orthopedic
Increased connective tissue collagen production
Carpal tunnel syndrome
Myopathy of proximal muscles Gastrointestinal Colon polyps Increased appetite Cutaneous
Malodorous and oily skin
Skin thinning

The unregulated hypersecretion of growth hormone by the anterior pituitary leads to the increased production of somatomedins, namely insulin-like growth factor-I (IGF-I), by the liver. Children, in whom the epiphyses have not closed, experience gigantism. Adults, in contrast, develop acromegaly. Approximately 98% of all acromegaly results from a pituitary adenoma. Growth hormone hypersecretion affects all tissues and organ systems in the body, including the heart, lungs, liver, and kidneys.
Cardiac disease is the most important cause of morbidity and mortality in acromegalic patients. 6, 7 Indeed, the most frequent cause of death in untreated acromegaly is cardiovascular, 8 with 50% of patients dying before the age of 50. Older reviews suggest that as many of 80% of patients died from cardiovascular complications before the age of 60. 9 A recent series suggested that as many as 10% of newly diagnosed patients may have overt heart failure upon initial diagnosis. 10 The most prominent feature of acromegalic cardiac disease is myocardial hypertrophy. 6 Left ventricular hypertrophy (LVH) can occur in the presence of systemic hypertension, but also occurs in at least 50% of normotensive acromegalic patients. Overall, two thirds of patients will have LVH at the time of diagnosis. 7 The prevalence of LVH increases with patient age and is greater than 90% in elderly patients with a long disease duration. 11 One study revealed that the prevalence of LVH is greater when left ventricular mass is indexed for height rather than for body surface area (BSA) in patients with active acromegaly. 11
Echocardiography reveals increases in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time. 12 These changes occur independently from systemic hypertension. 13 The combination of normal or increased systolic function and a high incidence of heart failure implies that, at least on initial presentation, many patients appear to be in high-output heart failure. Diastolic dysfunction is clearly an early sign of acromegalic cardiomyopathy. 14 A poorly compliant left ventricle and its accompanying need for high filling pressures may be considered the hallmark of acromegalic cardiomyopathy. Many patients will report decreases in exercise tolerance. Increases in heart rate during exercise decrease diastolic filling time, which leads to decreased stroke volume and cardiac output. Diastolic dysfunction may exist even in the absence of clinically appreciable left ventricular hypertrophy. 14 Although hypertrophy of the left ventricle may be prominent, evidence of right ventricular enlargement also exists. 15 Long disease duration may be associated with decreases in systolic function and cardiac output. Left ventricular size may return to normal after medical or surgical therapy; however, this is more common in young patients with a shorter disease duration. 16 Nevertheless, return of normal diastolic function may not occur and may reflect the persistence of interstitial myocardial fibrosis. 16 - 19
Valvular disease has become recognized as an important cause of ventricular dysfunction and heart failure in acromegaly. In one autopsy series, 19% of patients had mitral or aortic valve abnormalities. 20 Recently, Pereira et al found aortic regurgitation (> trace) in 30% and mitral regurgitation (> moderate) in 5% of acromegalic patients. 21 The prevalence of valvular disease was closely related to disease duration and the presence of LVH. In addition, Colao et al found mitral or aortic valve disease (including leaflet fibrosis and annular calcification) in 86% of patients with active, untreated acromegaly. 7 It is interesting to note that among patients with biochemical evidence of a “cure” for at least 1 year, the prevalence of such structural valve abnormalities remains high at 73%. Valvular disease is closely related to the presence of LVH; however, it is unclear why the incidence of valvular disease remains high despite a reduction in the prevalence of LVH. Regardless, changes in valvular architecture and function are more likely with a long disease duration and seem less likely to improve with medical or surgical therapy.
Although the larger, more proximal coronary arteries are rarely stenotic in acromegaly, coronary artery disease of the smaller vessels has been described. 20 Indeed, defects in myocardial perfusion have been described using single photon emission computed tomography (SPECT). 22 As such, the presence of angina should alert the physician to the possibility of myocardial ischemia, regardless of the patient’s age.
Classically, it had been thought that the incidence of supraventricular and ventricular ectopy was not increased in resting acromegalics 23 ; however, given the poor exercise tolerance of acromegalic patients and a lower threshold to what may be considered “exercise,” cardiac arrhythmias are frequently observed. In a recent case report, Holter monitoring of one newly diagnosed acromegalic patient revealed 17,249 premature ventricular complexes in a single day. 24 It is noteworthy that this number was decreased almost sixfold with 2 months of octreotide treatment. In addition to supraventricular and ventricular ectopy, disorders of the conduction system, such as bundle branch blocks, can also occur. 23, 25 EKG changes such as S-T segment depression, T-wave abnormalities, and increased QRS voltage are typical of LVH and are frequently observed.
After cardiovascular disease, respiratory disease is the most common cause of death in untreated acromegaly. Sleep apnea secondary to upper airway obstruction (obstructive sleep apnea or OSA) can affect up to 70% of acromegalic patients. 26 It is interesting to note that airway obstruction is threefold more common among male acromegalics than female acromegalics. 27 Nocturnal airway obstruction is not always reversed after surgical cure. 28 In addition to OSA, central respiratory depression of unknown etiology may also be noted. 27, 29 Pneumomegaly is observed in 50% of acromegalic patients 30 and ventilation-perfusion mismatching may also be increased.
Hypertrophy of the facial bones, especially the mandible, and coarsening of facial features lead to significant changes in patient appearance. Soft tissues of the nose, mouth, tongue, and lips become thicker and help give acromegalic patients their characteristic facade. In addition to the easily observed external changes, there is thickening of the laryngeal and pharyngeal soft tissues. 31 Hypertrophy of the periepiglottic folds, calcinosis of the larynx, 32 and recurrent laryngeal nerve injury can all contribute to airway obstruction and respiratory disease. Indeed, hypertrophy can cause significant reduction in the size of glottic opening. Laryngeal stenosis 33 and abnormal vocal cord function may be present and patients may report hoarseness or changes in vocal tone, quality, or strength. It is interesting to note that vocal cord function is quickly reversed and may return to normal within 10 days of surgery. 34
A high risk of perioperative airway compromise has been well documented in acromegalics with OSA. 35 As such, narcotics and benzodiazepines should be administered with caution to any acromegalic carrying the diagnosis of OSA. Given the high percentage of acromegalic patients with OSA and the fact that OSA is underdiagnosed in most patient populations, the prudent physician should attempt to elicit a history of OSA in all acromegalic patients. Any history of excessive daytime somnolence, snoring, or frank sleep apnea (often noted by the patient’s spouse) should alert the physician to the possibility of OSA, especially among male patients.

McCune-Albright Syndrome
Among children with gigantism, approximately 20% to 25% of patients have McCune-Albright syndrome (polyostotic fibrous dysplasia). In contrast to pituitary gigantism or acromegaly, growth hormone excess in McCune-Albright syndrome normally results from somatotroph hyperplasia; however, a pituitary adenoma may be present. This rare hypersecretory syndrome consists of polyostotic fibrous dysplasia, café au lait spots, sexual precocity, hyperthyroidism, hyperparathyroidism, and hyperprolactinemia. The anesthetic management of this rare disorder has been previously reviewed. 36 Patients may require a larger than expected endotracheal tube. Indeed, it may be more appropriate to select endotracheal tube size based upon patient height rather than patient age. Skeletal involvement, with associated fractures, bony deformities, and weakness, can be severe. Many patients may report orthopedic procedures. Patients with McCune-Albright syndrome may also exhibit signs and symptoms of Cushing’s disease secondary to ACTH-independent hypercortisolism.

Cushing’s Disease
Cushing’s disease specifically results from the unregulated hypersecretion of adrenocorticotropic hormone (ACTH) by a pituitary adenoma and consequent hypercortisolism. Cushing’s syndrome is more frequently encountered in clinical practice and may result from any number of conditions that result in hypercortisolism. Indeed, the most common cause of Cushing’s syndrome is iatrogenic. In Cushing’s disease, long-term exposure to excessive circulating glucocorticoids results in significant pathophysiology.
Systemic hypertension is among the most common manifestations of Cushing’s disease. Indeed, as many as 80% of patients with Cushing’s disease have systemic hypertension and 50% of untreated patients have severe hypertension with a diastolic blood pressure greater than 100 mm Hg. 37 Increased endogenous corticosteroids have been shown to cause systemic hypertension by a variety of mechanisms.
Hydrocortisone has been shown to increase cardiac output. 38 Increases in cardiac output may occur secondary to enhanced responses to endogenous catecholamines. Patients with Cushing’s disease have an increased expression of the angiotensinogen II (type I) receptor 39 and potentiation of inositol triphosphate production in vascular smooth muscle cells. 40 This leads to increased sensitivity to endogenous vasoconstrictors such as angiotensin II, epinephrine, and norepinephrine. Indeed, an enhanced chronotropic effect with isoproterenol infusion has been observed in patients with Cushing’s disease. In addition, patients exhibit an increased pressor response to norepinephine. 41
There is evidence that hypercortisolism leads to an increase in the hepatic production of angiotensinogen. 42 The increase in angiotensinogen activates the renin-angiotensin system, 42 which leads to angiotensin-mediated vasoconstriction as well as to an increase in plasma volume. In addition, the mineralocorticoid effects of cortisol and hydrocortisone lead directly to sodium and water retention. The classic presentation of a hypokalemic alkalosis is actually more common in Cushing’s syndrome, especially with ectopic ACTH production. Nitric oxide synthesis may be suppressed. 43 Supplementation with l -arginine can prevent hypertension in rats given ACTH, further suggesting that alterations in nitric oxide synthesis may be an important etiologic factor. 44 Alterations in diurnal blood pressure variation and attenuation in nighttime decreases in blood pressure have also been observed in patients with Cushing’s disease. 45
With hypertension ubiquitous among patients with Cushing’s disease, it is not surprising that LVH is also very common. Indeed, a high prevalence of LVH and concentric remodeling has been reported in Cushing’s disease. Using echocardiography, reduced midwall systolic performance and diastolic dysfunction can be observed in at least 40% of patients 46 and disproportionate hypertrophy of the intraventricular septum has been reported. 47, 48 Nevertheless, it should be noted that relative wall thickness (RWT) is not related to blood pressure levels. 49 As such, it seems likely that excess plasma cortisol may be at least a second causal factor. EKG abnormalities are common in patients with Cushing’s disease. High voltage QRS complexes and inverted T waves suggesting left ventricular hypertrophy and left ventricular strain have been described. 47 Despite resolution of many cardiovascular symptoms of disease upon successful resection of the adenoma, it is important to note that increases in cardiovascular morbidity and mortality persist for at least 5 years. 50
As in acromegaly, OSA is also common among patients with Cushing’s disease. Polysomnographic studies indicate that as many as 33% of patients with Cushing’s disease have mild sleep apnea and 18% of patients have severe sleep apnea. 51 Complaints of daytime sleepiness are very common. 51 Weight gain and centripetal obesity are commonly observed in Cushing’s disease. As obese patients are more likely to have OSA than nonobese patients, it seems that obesity may play a role in high prevalence of OSA observed among patients with Cushing’s disease. In addition, patients develop fat depots over the cheeks and temporal regions, giving rise to the rounded “moon-facies” characteristic of the disease. Whether these changes in the head and upper airway affect the incidence of OSA has not been investigated. The airway management of patients with a history of OSA may be challenging. 52 Tracheal intubation may be more difficult 53, 54 and these patients may be significantly more sensitive to sedative medications, 52, 55 including benzodiazepines and narcotic analgesics. As in acromegaly, narcotics and benzodiazepines should be used with great care and always during continuous monitoring by qualified personnel. It should be noted that a link between OSA and hypertension 56 has been well described.
Glucose intolerance occurs in at least 60% 57 of patients with Cushing’s disease, with overt diabetes mellitus present in up to one third of all patients. Indeed, there is evidence that a high prevalence of occult Cushing’s disease may exist among patients with diabetes mellitus, type II. 58 Patients taking oral hypoglycemic agents should be instructed not to take any such agent the morning of surgery because they will not be allowed to eat before the procedure. A significant portion of patients with Cushing’s disease, especially those with long-standing disease, may require insulin for glucose control. In such patients, avoidance of morning insulin the day of surgery may put the patient at risk for significant perioperative hyperglycemia. At the same time, the patient’s normal dose of insulin may put the fasting patient at risk for significant perioperative hypoglycemia. A reasonable compromise may include a lower dose of “long-acting” insulin preparations with preoperative blood sugar measurements guiding regular (or “fast-acting”) insulin therapy. Regardless, all patients with diabetes should have at least one blood glucose tested before surgery and at least one tested in the immediate postoperative period. It has been clearly established that hyperglycemia can aggravate ischemic injury in the brain and spinal cord. Although no randomized studies exist that demonstrate a “safe” level of hyperglycemia, current practice suggests that any blood glucose greater than 180 mg/dL (10.1 mmol/L) should be treated with insulin. One must always weigh the benefits of “tight” intraoperative glucose control against the risk of severe, unintentional hypoglycemia in an unconscious patient.
Diffuse osteoporosis may occur in up to 50% of patients having Cushing’s disease. 59 Almost 20% of patients may have pathologic fractures and many patients with long-standing Cushing’s syndrome have lost height because of osteoporotic vertebral collapse. 60 In addition, aseptic necrosis of the femoral and humeral heads can occur in Cushing’s syndrome. Particular care should be taken when positioning patients during surgery.
Many patients with Cushing’s disease report generalized weakness, and a myopathy of the proximal muscles of the lower limb and the shoulder girdle have been described. 60 The respiratory muscles can also be affected and patients can present in respiratory failure secondary to respiratory muscle weakness. 61 It is possible that muscle weakness may play a role in the prevalence of OSA among patients with Cushing’s disease (see earlier). Nevertheless, there are no data to suggest a change in the susceptibility to succinylcholine or nondepolarizing neuromuscular blockers.
Nephrolithiasis is common in Cushing’s disease and approximately 50% of active, untreated patients have detectable stones. 62 It is noteworthy that 27% of patients that had been surgically cured also had detectable stones. Systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role. 62 Infections are more common in patients with Cushing’s disease 63 ; however, an empiric change in usual perioperative antibiotics is unnecessary.
Hypercortisolism also results in skin thinning. 64 Patients may appear to have senile purpura with many small bruises and a loss of subcutaneous fat. Cannulation of superficial veins for intravenous access can be extremely difficult and minimal trauma may result in bruising.
The function of both the pituitary-thyroid axis and the pituitary-gonadal axis is suppressed in patients with Cushing’s syndrome because of a direct effect of cortisol on TSH 65 and gonadotrophin secretion. 66 Patients may therefore have signs and symptoms of thyroid or gonadal insufficiency. Exophthalmos secondary to increased retro-orbital fat deposition may be present in up to one third of patients with Cushing’s disease. 67 The anesthesiologist should be cognizant of the presence of exophthalmos; a corneal abrasion can be a painful complication of an otherwise successful surgery.

Prolactinomas are the most frequently observed type of hyperfunctioning pituitary adenoma and represent 20% to 30% of all clinically recognized tumors and half of all functioning tumors. In women, hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility. 68 Osteopenia may also be noted. 69 Hyperprolactinemia is frequently observed in polycystic ovarian syndrome (POS). 70 Obviously, it is important to differentiate POS from a prolactinoma.
In men, symptoms of hyperprolactinemia are relatively nonspecific and include decreased libido, impotence, premature ejaculation, erectile dysfunction, and oligospermia. Prolactin levels tend to be higher in men, regardless of whether macroadenoma or a microadenoma is present. 71 Owing to an earlier diagnosis in women, more than 90% of prolactin-secreting microadenomas are diagnosed in females. Macroadenomas are equally common in men and women. 71, 72 More than 90% of patients respond to medical therapy with a dopamine agonist such as bromocriptine or cabergoline 73 ; however, normalization of prolactin levels occurs more quickly in patients with microadenomas. 71 Nevertheless, few patients with a prolactinoma will come in for surgical excision. There are few anesthesia-specific ramifications of hyperprolactinemia and it will not be discussed further.

Thyrotropic (TSH-producing) Adenomas
Thyrotropic adenomas are rare and represent no more than 2.8% of all pituitary tumors. 74 The unregulated hypersecretion of TSH by a pituitary adenoma results in elevated thyroxine and clinical hyperthyroidism. Signs and symptoms of hyperthyroidism include palpitations, tachycardia, tremor, weight loss, difficulty sleeping, and heat intolerance. A goiter is commonly observed. As thyrotropic adenomas are extremely rare, most patients are often first treated for other causes of hyperthyroidism such as Graves disease. As such, these tumors are often allowed to grow and can be quite large upon diagnosis. The diagnosis is made by elevated serum thyroxine accompanied by inappropriately high TSH level in the presence of a pituitary adenoma.
Given the delay in diagnosis of these tumors and their large size, many patients often have symptoms related to the local mass effect of the tumor. In addition, more than 60% of thyrotrophic adenomas are locally invasive at the time of surgery. 75 The review of preoperative radiographic studies is critical to assess tumor size and invasiveness and to assess for the risk of blood loss. Hyperthyroidism should be controlled before a patient undergoes surgical resection. Antithyroid medication such as propylthiouracil may reduce thyroid hormone production, and somatostatin analogs such as octreotide can suppress TSH-production and may reduce tumor size. 76 The effects of hyperthyroidism on anesthesia have been discussed elsewhere. 77

Gonadotrophic Adenomas
Tumors producing sufficient follicle-stimulating hormone (FSH), luteinizing hormone (LH), or α-subunit are rarely associated with any specific symptoms. Most gonadotrophic tumors are clinically nonfunctioning and will be discovered incidentally or secondary to local mass effects as described previously. High serum FSH may cause chronic ovarian hyperstimulation and chronic pelvic pain in young women 78 and men may have high serum testosterone.

Nonfunctioning Tumors: Nonfunctioning Adenomas, Rathke Cleft Cyst, Craniopharyngioma
Nonfunctioning (null cell) adenomas are the second most common type of pituitary tumors, accounting for 20% to 25% of pituitary adenomas. Craniopharyngiomas and Rathke cleft cysts are less common. As each of these tumors is not associated with the hypersecretion of a hormone, they almost always have symptoms related to local mass effects (see previous discussion). Patients must be evaluated for hypopituitarism, and associated hypothyroidism and adrenal insufficiency must be evaluated before surgery. Many patients will have mild hyperprolactinemia secondary to the so-called “stalk effect.” This results from disinhibition of prolactin secretion secondary to a decrease in dopamine-mediated tonic inhibition of prolactin release. Treatment with dopamine analogs, such as bromocriptine or cabergoline, may result in symptomatic relief (at least from symptoms related to hyperprolactinemia). Posterior pituitary dysfunction and diabetes insipidus (DI) can also occur but is much less common.

Intraoperative Management
Plans for the intraoperative anesthetic management of patients undergoing transsphenoidal surgery should be based upon the assessment of each patient’s individual disease process. Successful intraoperative management includes an understanding of techniques for successful airway management and placement of appropriate monitors. Selection of anesthetic agents should be tailored to facilitate surgical exposure, preserve cerebral perfusion and oxygenation, and provide for rapid emergence and neurological assessment.

The placement of invasive monitoring should always be based on each patient’s preoperative assessment. Given that cardiovascular disease often occurs with both Cushing’s disease and acromegaly, an arterial catheter may be indicated. In addition, transsphenoidal surgery can be associated with significant intraoperative hemodynamic changes (see later discussion). 79 - 81 Indeed, an arterial line may allow for earlier diagnosis and treatment of both hypotension and hypertension. Nevertheless, reserve an arterial catheter for patients with poor exercise tolerance, patients with signs and symptoms of congestive heart failure, or patients with documented cardiomyopathy. Indeed, there is no evidence that excessive hemodynamic instability accompanies acromegaly in the absence of specific cardiovascular disease. 82
It should be noted that secondary to soft tissue overgrowth, blood flow through the ulnar artery may be compromised in up to 50% of acromegalic patients. 83 Thus blood flow to the hand can be entirely dependent on collateral radial flow. The presence or history of carpal tunnel syndrome (median thenar neuropathy) makes this more likely. In such patients, placement of a radial artery catheter may be unnecessarily risky. The consideration of alternative sites (e.g., femoral) for intra-arterial monitoring should be considered.
Generally speaking, central venous pressure (CVP) or pulmonary artery pressure (PAP) monitoring is not necessary in transsphenoidal surgery. In any patient with cardiovascular disease significant enough to necessitate CVP or PAP monitoring, medical therapy to abrogate cardiovascular disease should be initiated until the patient is a better candidate for elective surgery. Should the patient require surgery emergently (for increased ICP, pituitary apoplexy, etc.), it should be noted that in patients with a cardiomyopathy that a pulmonary artery catheter (PAC) may be a better monitor of left ventricular preload; however, this correlation has been challenged. 84 Central venous access may be necessary in some patients, particularly those with Cushing’s disease where cannulation of peripheral veins can be difficult.

Airway Management
As noted above, acromegaly induces significant changes in airway anatomy. Indeed, successful endotracheal intubation and management of the acromegalic airway can be extremely difficult. 31, 85, 86 As might be expected, difficult laryngoscopy and poor laryngeal view has been associated with Mallampati class 3 and 4 airway examinations; however, 20% of acromegalic patients assessed as Mallampati class 1 and 2 have been noted to be difficult to intubate. 86 As such, the Mallampati classification has poor “negative predictive value,” and difficult endotracheal intubation may be unpredictable in acromegalic patients. Indeed, routine tracheostomy 87 had been historically advocated for management of the acromegalic airway; however, this is rarely necessary. 88, 89 The anesthesiologist should approach any acromegalic airway, regardless of anticipated difficulty, with extreme caution. Flexible fiberoptic laryngoscopy can be more difficult. 90 A large variety of alternative airway management tools should be readily available ( Figures 3-1 , 3-2 , 3-3 , and 3-4 ). The Parker Flex-Tip ( Figure 3-5 ) endotracheal tube is associated with higher success rates during fiberoptic tracheal intubation compared with standard endotracheal tubes 91 and may be particularly useful in acromegalic patients with laryngeal stenosis. The intubating Laryngeal Mask Airway (Fast-Trach LMA, Figures 3-1 and 3-2 ), has been associated with a low (52.6%) first-attempt success rate in unparalyzed acromegalic patients. 92 As always, awake techniques offer the greatest margin of safety.

Figure 3-1 The intubating laryngeal mask airway (Fastrach TM LMA) is available in many different sizes.

Figure 3-2 The intubating laryngeal mask airway (Fast-Trach LMA) with an endotracheal tube in place. The Fast-Trach LMA is unique in that it allows for the patient to be ventilated during the process of intubation.

Figure 3-3 The Bullard intubating laryngoscope allows for indirect laryngoscopy and may be particularly useful in patients with limited neck extension.

Figure 3-4 A lighted stylet or “light wand.”

Figure 3-5 The Parker Flex Tip tube is pictured on an adult bronchoscope. The “beak” allows for easier passage into the trachea.
Both OSA 53, 54 and obesity 93 are known to be associated with difficult endotracheal intubation. Although Cushing’s disease is strongly associated with both OSA and obesity, there are no data to suggest that Cushing’s disease represents an independent risk factor for a difficult intubation. Nevertheless, the airway should be approached with caution in patients with Cushing’s disease. The presence of diabetes should also suggest the possible presence of gastroesophageal reflux disease 94 (GERD) and slowed gastric emptying and the possible need for a rapid sequence induction. The intubating Laryngeal Mask Airway ( Figures 3-1 and 3-2 ) may be particularly useful in morbidly obese patients 95 ; however, use of a lighted stylet or “light wand” ( Figure 3-4 ) may be difficult in obese patients. Use of the Bullard laryngoscope may attenuate the cardiovascular response to laryngoscopy. 96
No changes in airway anatomy have been reported in patients with prolactinomas or in patients with nonfunctioning tumors. Nevertheless, every surgical patient deserves a thorough airway examination and plans for airway management should be individualized.
Intubation with a standard endotracheal tube is acceptable and should allow the surgeon adequate space to complete the procedure. Some surgeons prefer intubation with an oral RAE tube. Obviously, nasal intubation is contraindicated. 97 The endotracheal tube and the anesthetic circuit should be secured away from the surgical field, on the opposite side of the mouth from where the surgeon will stand.

Positioning and Preparation for Surgery
After the induction of anesthesia and tracheal intubation, the patient is positioned for surgery. Transsphenoidal operations are generally performed with the patient supine with some degree of head-up position. The neck is extended and the head is turned slightly to facilitate surgical access to both nares. Any time the operative field is above the right atrium, venous air embolism (VAE) is a theoretical risk. Echocardiography, precordial Doppler, and end-tidal N 2 monitoring may be considered. Although a 10% risk of VAE in the semiseated position has been reported, 98 a clinically significant VAE associated with significant morbidity or mortality has not been reported. At our institution, we have anesthetized more than 4000 patients for transsphenoidal surgery and have not had a clinically significant VAE. Consequently, routine monitoring with capnography seems adequate in our experience.
Any surgical procedure conducted around the patient’s head can result in unintended injury to the eyes. Consequently, protective disposable goggles should be used. Many surgeons will wrap the upper portion of the head, including the eyes, with a towel to keep hair from falling into the surgical field. Care should be taken not to secure the towel too tightly as excessive pressure on the eyes could result in central retinal artery occlusion or ischemic optic neuropathy. An oral temperature probe should be positioned in the esophagus before the placement of a throat pack. Attempts to position a temperature probe after the throat pack is in place may result in pushing the throat pack down to the distal esophagus or stomach where retrieval may be more difficult.
Topical application or injection of local anesthetic and epinephrine solutions to the mucosal surfaces of the nose are commonly employed during surgical preparation. Cocaine may also be used, 99 but many physicians prefer lidocaine-epinephrine mixtures. 100 The application of vasoconstrictors serves to shrink mucosa and reduces bleeding. The addition of lidocaine to epinephrine has been shown to increase the arrhythmogenic threshold dose of epinephrine when compared with epinephrine in saline. 101 Furthermore, a comparison of 0.5% versus 1% lidocaine, used with the same concentration of epinephrine, indicated that mucosal infiltration with the higher dose lidocaine led to more stable hemodynamics. 102 Nevertheless, the potential for dysrhythmias or hypertension persists in the presence or absence of inhaled anesthetics. 79 - 81 Hypertension can be significant and myocardial ischemia with cardiac troponin elevation has been reported in patients without coronary artery disease. 81 Hypertension may be successfully treated with intravenous agents such as nitroglycerin, nitroprusside, or phentolamine. Hypertension is normally transient and should be treated with short-acting agents to avoid “rebound” hypotension after the vasoconstrictive effects of epinephrine have ended. Esmolol may be useful in tachycardic patients; however, it should be avoided in bradycardic patients. Profound alpha-adrenergic stimulation may result in hypertension and reflex bradycardia. In such patients, beta-blockade may induce asystole. Anticipating hypertension and increasing the patient’s depth of anesthesia may be an adequate solution.
Possible complications from the injection of local anesthetic include total spinal anesthesia. This can occur if local anesthetic is inadvertently injected through the cribriform plate. 103 Should this occur, sudden bradycardia or hypotension suggests sympathetic blockade and resuscitation with fluid, epinephrine, and atropine may be necessary. Ventilatory support at the end of the case may also be required.
Many surgeons will place a lumbar intrathecal catheter to assist in visualization of the tumor. The catheter can be used to manipulate cerebrospinal fluid pressure (CSF) pressure by the injection of saline or aspiration of CSF. In patients with large macroadenomas with significant suprasellar extension, some pituitary surgeons will inject intrathecal air. The air serves to increase CSF pressure and may “push” the suprasellar portion of the tumor into the operative field. The injected air may also serve to outline a tumor, allowing for fluoroscopic visualization. Obviously, strict asepsis should be used when anything is injected into the CSF.

Operative Management
There is a broad range of acceptable anesthetics for pituitary surgery. Any anesthetic appropriate for intracranial surgery is acceptable for transsphenoidal surgery. Anesthetic selection should be based upon an understanding of the patient’s anesthetic history, medical co-morbidities, and neurological disease. Anesthetic agents should be selected and anesthesia should be managed to provide for rapid emergence and neurological assessment. Gross visual field testing to ensure the postoperative integrity of the optic nerves is critical; any patient with a decrease in vision should be emergently reexplored.
The desire for rapid emergence makes techniques using rapidly metabolized agents such as propofol and remifentanil or inhalational agents with low blood solubility such as sevoflurane, reasonable choices. The merits of intravenous versus inhalation techniques for surgery has been studied 104 and reviewed 105 elsewhere. Inhalational anesthesia supplemented with remifentanil may provide for greater hemodynamic stability and an earlier neurological examination. 106 If remifentanil is used, it is important to provide transitional analgesia with a longer-acting opioid, otherwise emergence may be complicated by patient pain. Neuromuscular blockade should be maintained throughout the procedure as any patient movement during surgery could lead to significant patient injury.
If intrathecal air is injected as described above, it seems prudent to discontinue nitrous oxide. Unlike in supratentorial or posterior fossa surgery where any extradural or subdural air can be “vented” to the atmosphere, any air injected into the CSF will have to be reabsorbed. As nitrogen is extremely insoluble in blood, this can take several days. The use of nitrous oxide can expand the volume of the trapped air space and possibly result in intracranial hypertension. Some authors avoid nitrous oxide in any “head-up” neurosurgical procedure secondary to the possible risk of VAE; however, there are no data to support this practice.
Some investigators have found intraoperative visual evoked potential (VEP) monitoring to be useful in procedures near the visual pathway. Conceptually, VEP monitoring is very simple. A bright flash of light periodically stimulates the eyes. The bright flash evokes an electrical response in the occipital cortex. The electrical response is recorded by scalp electrodes and is monitored over the course of the procedure. As such, VEPs continually monitor the integrity of visual pathway during surgery. Although conceptually useful, VEPs are difficult to use in practice. Goggles placed over the patient’s closed eyes to deliver bright flashes of light can be cumbersome and can interfere with surgical access. In addition, VEPs are extremely sensitive to the effects of anesthetic agents. Indeed, even narcotic-induced papillary constriction can interfere with appropriate stimulation of the retina. 107 Nevertheless, a small retrospective study indicated that patients with a preoperative visual field deficit who have intraoperative VEP monitoring have greater postoperative visual field improvements 108 ; however, no benefit in postoperative visual acuity was noted. Given the lack of strong evidence to support routine use and the high “false-positive rate” secondary to intense anesthetic sensitivity, routine use of VEP monitoring during transsphenoidal surgery seems unnecessary.
Transsphenoidal pituitary surgery is normally associated with minimal blood loss; however, there is a potential for significant hemorrhage given the proximity of the pituitary to the carotid arteries. Indeed, carotid artery injury is an infrequent but potentially fatal complication of transsphenoidal surgery. 109 Growth hormone–secreting tumors can be associated with impressive dilatation of the intracranial arteries, theoretically increasing the risk for intraoperative hemorrhage. In the case of inadvertent arterial injury, immediate communication among the surgeon, the anesthesiologist, and other members of the operating room team is imperative. The operative field is extremely narrow and even small amounts of blood in the field may make repair difficult. Deliberate hypotension may improve visualization and facilitate repair. Suturing the injury may prove difficult and compression with hemostatic agents and autologous muscle may be necessary. A balloon catheter can be inflated and placed in the region for additional tamponade. 110 Postoperative angiography is essential to rule out pseudoaneurysm formation and to allow for endovascular techniques of hemostasis and repair.
Moderate venous “oozing” from the cavernous sinus is a more common problem in clinical practice. As noted above, the operative field is narrow and even small amounts of blood can make surgery more difficult. Attempts to reduce venous bleeding by lowering CVP and keeping the patient “dry” have no proven efficacy. In fact, tumor size and the presence of suprasellar extension seem to be the primary determinants of blood loss. 111 As such, there is no need to keep patients “dry” in hopes of reducing cavernous sinus pressure and blood loss. In patients with large tumors or whenever excessive blood loss is anticipated, large bore intravenous access should be secured before surgical incision, and blood products should be readily available.
After successful resection of the tumor, a Valsalva maneuver may be used to test for a CSF leak. If a CSF leak is readily observed, most neurosurgeons will pack the sella with autologous fat before it is reconstructed. In addition, a lumbar drain (if placed before incision) may be used to control CSF pressure.
Upon completion of the procedure, any coughing may reopen a CSF leak or produce undesired increases in ICP. A smooth emergence from anesthesia is desirable to prevent such complications. The patient’s muscle relaxation should be reversed with an anticholinesterase agent. If a pharyngeal throat pack has been placed previously to prevent accumulation of blood in the stomach, it should be removed. All patients will benefit from orogastric (OG) suctioning to remove blood from the stomach. If used, the OG tube should be removed while the patient is still well anesthetized to prevent coughing or vomiting. Care should be taken to make sure that the OG tube passes down into the stomach and not up into the surgical field. All patients will have a bony defect and intracranial placement of an OG tube may result in significant patient injury. The oropharynx should also be suctioned meticulously. During emergence, patients should be reminded to breathe through their mouths. Nasal packing will make nose breathing impossible and an oral airway may facilitate mouth breathing. Patients prone to upper airway obstruction may benefit from extubation in a seated position.

Postoperative Considerations
The postoperative care of any patient that has undergone transsphenoidal surgery mirrors the care of any patient that has undergone surgical resection of an intracranial mass. Care must taken to provide patients with adequate pain control and prophylaxis against nausea and vomiting while screening for serious complications including bleeding, CSF leakage, and cranial nerve injury. In addition, the clinician must be aware of the disorders of water balance, including diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and hypopituitarism.

Pain Control
Transsphenoidal surgery is normally associated with only moderate patient discomfort. Nevertheless, the most frequent complaint after transsphenoidal surgery is headache. In the immediate postoperative period, headache may be treated with opioids such as morphine, hydromorphone, or fentanyl. As noted earlier, narcotics should be used with great care in any patient with a history of OSA. Intravenous nonsteroidal drugs, such as ketorolac, may also be useful; however, many clinicians may choose to avoid them secondary to concerns about affects on platelet function. An unpublished review of 1000 patients who underwent transsphenoidal surgery at the University of Virginia failed to detect any bleeding complications among patients treated with ketorolac.

Nausea and Vomiting
Nausea and vomiting are very common postoperative complications in patients undergoing neurosurgical procedures, with nearly 40% of patients reporting either complaint. 112 Given the high risk for vomiting in patients after transsphenoidal surgery and the detrimental effect of vomiting on ICP, routine pharmacologic prophylaxis seems reasonable. Surgery on large sellar tumors with suprasellar extension and any operation where an intraoperative CSF leak was observed seem to be associated with significant increases in the incidence of vomiting. 113 At this point, there is no data to suggest that any one pharmacological agent are more efficacious than any other. In fact, a recent study of over 5000 general surgical patients found similar efficacy among ondansetron, dexamethasone, and droperidol. 114 Agent selection should be based on patient history and clinician preference.

Cranial Nerve Dysfunction and CSF Leakage
In the immediate postoperative period, all patients should undergo a thorough neurological assessment with special attention to cranial nerve function and visual field testing. As noted earlier, damage to the visual tract, notably the optic chiasm, is a feared complication of transsphenoidal surgery. Cranial nerves III-VI are also in close proximity to the pituitary gland and any cranial nerve palsy should be addressed with emergent reexploration or radiographic investigation including computed tomography (CT) or magnetic resonance imaging (MRI).
As noted above, patients with a CSF leak that is recognized intraoperatively should have the sella packed with autologous fat before closure. Nevertheless, some CSF leaks will not appear until the postoperative period. Such patients will complain of rhinorrhea or fluid leakage down the back of the throat. Suspicious drainage should be collected and sent to the laboratory for further investigation. CSF will test positive for tau-transferrin whereas nasopharyngeal secretions will not. If the patient is found to have a CSF leak, operative repacking and/or lumbar drainage should be considered.

Disorders of Water Balance
Disorders of water balance resulting from posterior pituitary dysfunction and abnormalities of antidiuretic hormone (ADH) secretion are not uncommon after transsphenoidal surgery. Neurogenic DI results from inadequate secretion of ADH. Postoperative DI normally manifests in the first 24 to 48 hours following surgery. Patients will complain of polyuria and polydipsia. The urine is typically dilute, with a specific gravity less than 1.005. It is important to distinguish DI from other commonly encountered processes seen in the postoperative period including iatrogenic perioperative fluid administration, glycosuria, and acromegalic diuresis. 115 If DI is diagnosed, most patients will be able to maintain intravascular volume if allowed to drink freely. If patients are unable to match urine losses with oral intake, treatment with desmopressin (DDAVP) should be considered. 116 If DDAVP is used, it is important to follow serum sodium and osmolarity to prevent “overshoot” hyponatremia. Fortunately, DI is normally only transient following surgery. 117
SIADH results from “inappropriately” high ADH secretion that leads to decreased free water excretion by the kidney. Urine output is low compared with intake and the urine is hyperosmolar with a high sodium concentration. Patients may complain of malaise, nausea, and weakness; however, many will be totally asymptomatic. Given the nonspecific presentation, it is important to rule out causes of hyponatremia from cortisol deficiency and hypothyroidism. Patients may have seizures if hyponatremia becomes severe. If SIADH is diagnosed, fluid restriction remains an important part of therapy. 118, 119 Hypertonic saline (3% or 1.8% saline) can be added to fluid restriction to help restore serum sodium in severely hyponatremic patients 120 ; however, it is important to avoid rapid correction to prevent central pontine myelinolysis. Some patients may benefit from treatment with intravenous urea. 121 In any patient with SIADH, frequent monitoring of fluid and electrolyte status is an essential component of therapy.


1. Mindermann T., Wilson C.B. Age-related and gender-related occurrence of pituitary adenomas. Clin. Endocrinol. (Oxf.) . 1994;41(3):359-364.
2. Burrow G.N., Wortzman G., Rewcastle N.B., et al. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N. Engl. J. Med. . 1981;304(3):156-158.
3. Elster A.D. Modern imaging of the pituitary. Radiology . 1993;187(1):1-14.
4. Vance M.L. Treatment of patients with a pituitary adenoma: one clinician’s experience. Neurosurg. Focus . 2004;16(4):1-6.
5. Ellegala D.B., Alden T.D., Couture D.E., et al. Anemia, testosterone, and pituitary adenoma in men. J. Neurosurg. . 2003;98(5):974-977.
6. Matta M.P., Caron P. Acromegalic cardiomyopathy: a review of the literature. Pituitary . 2003;6(4):203-207.
7. Colao A., Marzullo P., Di Somma C., et al. Growth hormone and the heart. Clin. Endocrinol. (Oxf.) . 2001;54(2):137-154.
8. Rajasoorya C., Holdaway I.M., Wrightson P., et al. Determinants of clinical outcome and survival in acromegaly. Clin. Endocrinol. (Oxf.) . 1994;41(1):95-102.
9. Corville C., Mason W.R. The heart in acromegaly. Arch. Intern. Med. . 1938;61:704-713.
10. Damjanovic S.S., Neskovic A.N., Petakov M.S., et al. High output heart failure in patients with newly diagnosed acromegaly. Am. J. Med. . 2002;112(8):610-616.
11. Vitale G., Galderisi M., Pivonello R., et al. Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass. Clin. Endocrinol. (Oxf.) . 2004;60(3):343-349.
12. Lopez-Velasco R., Escobar-Morreale H.F., Vega B., et al. Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension? J. Clin. Endocrinol. Metab. . 1997;82(4):1047-1053.
13. Ciulla M., Arosio M., Barelli M.V., et al. Blood pressure-independent cardiac hypertrophy in acromegalic patients. J. Hypertens. . 1999;17(12 pt 2):1965-1969.
14. Herrmann B.L., Bruch C., Saller B., et al. Acromegaly: evidence for a direct relation between disease activity and cardiac dysfunction in patients without ventricular hypertrophy. Clin. Endocrinol. (Oxf.) . 2002;56(5):595-602.
15. Fazio S., Cittadini A., Sabatini D., et al. Evidence for biventricular involvement in acromegaly: a Doppler echocardiographic study. Eur. Heart J. . 1993;14(1):26-33.
16. Colao A., Marzullo P., Cuocolo A., et al. Reversal of acromegalic cardiomyopathy in young but not in middle-aged patients after 12 months of treatment with the depot long-acting somatostatin analogue octreotide. Clin. Endocrinol. (Oxf.) . 2003;58(2):169-176.
17. Rossi E., Zuppi P., Pennestri F., et al. Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active and surgically treated disease. Chest . 1992;102(4):1204-1208.
18. Lombardi G., Colao A., Marzullo P., et al. Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study. J. Endocrinol. Invest. . 2002;25(11):971-976.
19. Colao A., Cuocolo A., Marzullo P., et al. Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance. J. Clin. Endocrinol. Metab. . 2001;86(4):1551-1557.
20. Lie J.T. Pathology of the heart in acromegaly: anatomic findings in 27 autopsied patients. Am. Heart J. . 1980;100(1):41-52.
21. Pereira A.M., van Thiel S.W., Lindner J.R., et al. Increased prevalence of regurgitant valvular heart disease in acromegaly. J. Clin. Endocrinol. Metab. . 2004;89(1):71-75.
22. Herrmann B.L., Brandt-Mainz K., Saller B., et al. Myocardial perfusion abnormalities in patients with active acromegaly. Horm. Metab. Res. . 2003;35(3):183-188.
23. Kahaly G., Olshausen K.V., Mohr-Kahaly S., et al. Arrhythmia profile in acromegaly. Eur. Heart J. . 1992;13(1):51-56.
24. Tachibana H., Yamaguchi H., Abe S., et al. Improvement of ventricular arrhythmia by octreotide treatment in acromegalic cardiomyopathy. Jpn. Heart J. . 2003;44(6):1027-1031.
25. Rodrigues E.A., Caruana M.P., Lahiri A., et al. Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle. Br. Heart J. . 1989;62(3):185-194.
26. Guilleminault C., van den Hoed J. Acromegaly and narcolepsy. Lancet . 1979;2(8145):750-751.
27. Fatti L.M., Scacchi M., Pincelli A.I., et al. Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly. Pituitary . 2001;4(4):259-262.
28. Pelttari L., Polo O., Rauhala E., et al. Nocturnal breathing abnormalities in acromegaly after adenomectomy. Clin. Endocrinol. (Oxf.) . 1995;43(2):175-182.
29. Perks W.H., Horrocks P.M., Cooper R.A., et al. Sleep apnoea in acromegaly. Br. Med. J. . 1980;280(6218):894-897.
30. Iandelli I., Gorini M., Duranti R., et al. Respiratory muscle function and control of breathing in patients with acromegaly. Eur. Respir. J. . 1997;10(5):977-982.
31. Kitahata L.M. Airway difficulties associated with anaesthesia in acromegaly. Three case reports. Br. J. Anaesth. . 1971;43(12):1187-1190.
32. Edge W.G., Whitwam J.G. Chondro-calcinosis and difficult intubation in acromegaly. Anaesthesia . 1981;36(7):677-680.
33. Williams R.G., Richards S.H., Mills R.G., et al. Voice changes in acromegaly. Laryngoscope . 1994;104(4):484-487.
34. Wilson C.B. Role of surgery in the management of pituitary tumors. Neurosurg. Clin. N. Am. . 1990;1(1):139-159.
35. Piper J.G., Dirks B.A., Traynelis V.C., et al. Perioperative management and surgical outcome of the acromegalic patient with sleep apnea. Neurosurgery . 1995;36(1):70-74. discussion 74–75
36. Langer R.A., Yook I., Capan L.M. Anesthetic considerations in McCune-Albright syndrome: case report with literature review. Anesth. Analg. . 1995;80(6):1236-1239.
37. Ross E.J., Marshall-Jones P., Friedman M. Cushing’s syndrome: diagnostic criteria. Q. J. Med. . 1966;35(138):149-192.
38. Pirpiris M., Yeung S., Dewar E., et al. Hydrocortisone-induced hypertension in men. The role of cardiac output. Am. J. Hypertens. . 1993;6(4):287-294.
39. Sato A., Suzuki H., Murakami M., et al. Glucocorticoid increases angiotensin II type 1 receptor and its gene expression. Hypertension . 1994;23(1):25-30.
40. Sato A., Suzuki H., Iwaita Y., et al. Dexamethasone potentiates production of inositol trisphosphate evoked by endothelin-1 in vascular smooth muscle cells. J. Cardiovasc. Pharmacol. . 1992;20(2):290-295.
41. Heaney A.P., Hunter S.J., Sheridan B., et al. Increased pressor response to noradrenaline in pituitary dependent Cushing’s syndrome. Clin. Endocrinol. (Oxf.) . 1999;51(3):293-299.
42. Mantero F., Boscaro M. Glucocorticoid-dependent hypertension. J. Steroid Biochem. Mol. Biol. . 1992;43(5):409-413.
43. Kelly J.J., Tam S.H., Williamson P.M., et al. The nitric oxide system and cortisol-induced hypertension in humans. Clin. Exp. Pharmacol. Physiol. . 1998;25(11):945-946.
44. Turner S.W., Wen C., Li M., et al. L-arginine prevents corticotropin- induced increases in blood pressure in the rat. Hypertension . 1996;27(2):184-189.
45. Zelinka T., Strauch B., Pecen L., et al. Diurnal blood pressure variation in pheochromocytoma, primary aldosteronism and Cushing’s syndrome. J. Hum. Hypertens. . 2004;18(2):107-111.
46. Muiesan M.L., Lupia M., Salvetti M., et al. Left ventricular structural and functional characteristics in Cushing’s syndrome. J. Am. Coll. Cardiol. . 2003;41(12):2275-2279.
47. Sugihara N., Shimizu M., Kita Y., et al. Cardiac characteristics and postoperative courses in Cushing’s syndrome. Am. J. Cardiol. . 1992;69(17):1475-1480.
48. Sugihara N., Shimizu M., Shimizu K., et al. Disproportionate hypertrophy of the interventricular septum and its regression in Cushing’s syndrome. Report of three cases. Intern. Med. . 1992;31(3):407-413.
49. Fallo F., Budano S., Sonino N., et al. Left ventricular structural characteristics in Cushing’s syndrome. J. Hum. Hypertens. . 1994;8(7):509-513.
50. Colao A., Pivonello R., Spiezia S., et al. Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J. Clin. Endocrinol. Metab. . 1999;84(8):2664-2672.
51. Shipley J.E., Schteingart D.E., Tandon R., et al. Sleep architecture and sleep apnea in patients with Cushing’s disease. Sleep . 1992;15(6):514-518.
52. Boushra N.N. Anaesthetic management of patients with sleep apnoea syndrome. Can. J. Anaesth. . 1996;43(6):599-616.
53. Siyam M.A., Benhamou D. Difficult endotracheal intubation in patients with sleep apnea syndrome. Anesth. Analg. . 2002;95(4):1098-1102.
54. Hiremath A.S., Hillman D.R., James A.L., et al. Relationship between difficult tracheal intubation and obstructive sleep apnoea. Br. J. Anaesth. . 1998;80(5):606-611.
55. Ostermeier A.M., Roizen M.F., Hautkappe M., et al. Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea. Anesth. Analg. . 1997;85(2):452-460.
56. Wolk R., Shamsuzzaman A.S., Somers V.K. Obesity, sleep apnea, and hypertension. Hypertension . 2003;42(6):1067-1074.
57. Smith M., Hirsch N.P. Pituitary disease and anaesthesia. Br. J. Anaesth. . 2000;85(1):3-14.
58. Catargi B., Rigalleau V., Poussin A., et al. Occult Cushing’s syndrome in type-2 diabetes. J. Clin. Endocrinol. Metab. . 2003;88(12):5808-5813.
59. Kaltsas G., Manetti L., Grossman A.B. Osteoporosis in Cushing’s syndrome. Front. Horm. Res. . 2002;30:60-72.
60. Ross E.J., Linch D.C. Cushing’s syndrome—killing disease: discriminatory value of signs and symptoms aiding early diagnosis. Lancet . 1982;2(8299):646-649.
61. Blanco C., Marazuela M., Flores J., et al. Severe respiratory failure secondary to Cushing’s myopathy. J. Endocrinol. Invest. . 2001;24(8):618-621.
62. Faggiano A., Pivonello R., Melis D., et al. Nephrolithiasis in Cushing’s disease: prevalence, etiopathogenesis, and modification after disease cure. J. Clin. Endocrinol. Metab. . 2003;88(5):2076-2080.
63. Graham B.S., Tucker W.S.Jr. Opportunistic infections in endogenous Cushing’s syndrome. Ann. Intern. Med. . 1984;101(3):334-338.
64. Ferguson J.K., Donald R.A., Weston T.S., et al. Skin thickness in patients with acromegaly and Cushing’s syndrome and response to treatment. Clin. Endocrinol. (Oxf.) . 1983;18(4):347-353.
65. Benker G., Raida M., Olbricht T., et al. TSH secretion in Cushing’s syndrome: relation to glucocorticoid excess, diabetes, goitre, and the “sick euthyroid syndrome”. Clin. Endocrinol. (Oxf.) . 1990;33(6):777-786.
66. Saketos M., Sharma N., Santoro N.F. Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids. Biol. Reprod. . 1993;49(6):1270-1276.
67. Panzer S.W., Patrinely J.R., Wilson H.K. Exophthalmos and iatrogenic Cushing’s syndrome. Ophthal. Plast. Reconstr. Surg. . 1994;10(4):278-282.
68. Schlechte J.A. Clinical practice. Prolactinoma. N. Engl. J. Med. . 2003;349(21):2035-2041.
69. Klibanski A., Neer R.M., Beitins I.Z., et al. Decreased bone density in hyperprolactinemic women. N. Engl. J. Med. . 1980;303(26):1511-1514.
70. Franks S. Polycystic ovary syndrome. N. Engl. J. Med. . 1995;333(13):853-861.
71. Colao A., Sarno A.D., Cappabianca P., et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur. J. Endocrinol. . 2003;148(3):325-331.
72. Melmed S., Braunstein G.D., Chang R.J., et al. Pituitary tumors secreting growth hormone and prolactin. Ann. Intern. Med. . 1986;105(2):238-253.
73. Colao A., Vitale G., Cappabianca P., et al. Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J. Clin. Endocrinol. Metab. . 2004;89(4):1704-1711.
74. Mindermann T., Wilson C.B. Thyrotropin-producing pituitary adenomas. J. Neurosurg. . 1993;79(4):521-1517.
75. Brucker-Davis F., Oldfield E.H., Skarulis M.C., et al. Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J. Clin. Endocrinol. Metab. . 1999;84(2):476-486.
76. Caron P., Arlot S., Bauters C., et al. Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas. J. Clin. Endocrinol. Metab. . 2001;86(6):2849-2853.
77. Farling P.A. Thyroid disease. Br. J. Anaesth. . 2000;85(1):15-28.
78. Valimaki M.J., Tiitinen A., Alfthan H., et al. Ovarian hyperstimulation caused by gonadotroph adenoma secreting follicle-stimulating hormone in 28-year-old woman. J. Clin. Endocrinol. Metab. . 1999;84(11):4204-4208.
79. Keegan M.T., Atkinson J.L., Kasperbauer J.L., et al. Exaggerated hemodynamic responses to nasal injection and awakening from anesthesia in a cushingoid patient having transsphenoidal hypophysectomy. J. Neurosurg. Anesthesiol. . 2000;12(3):225-229.
80. Pasternak J., Atkison J., Kasperbauer J., et al. Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients. J. Neurosurg. Anesthesiol. . 2004;16(3):189-195.
81. Chelliah Y.R., Manninen P.H. Hazards of epinephrine in transsphenoidal pituitary surgery. J. Neurosurg. Anesthesiol. . 2002;14(1):43-46.
82. Seidman P.A., Kofke W.A., Policare R., et al. Anaesthetic complications of acromegaly. Br. J. Anaesth. . 2000;84(2):179-182.
83. Campkin T.V. Radial artery cannulation. Potential hazard in patients with acromegaly. Anaesthesia . 1980;35(10):1008-1009.
84. Kumar A., Anel R., Bunnell E., et al. Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Crit. Care. Med. . 2004;32(3):691-699.
85. Messick J.M.Jr., Cucchiara R.F., Faust R.J. Airway management in patients with acromegaly. Anesthesiology . 1982;56(2):157.
86. Schmitt H., Buchfelder M., Radespiel-Troger M., et al. Difficult intubation in acromegalic patients: incidence and predictability. Anesthesiology . 2000;93(1):110-114.
87. Southwick J.P., Katz J. Unusual airway difficulty in the acromegalic patient—indications for tracheostomy. Anesthesiology . 1979;51(1):72-73.
88. Ovassapian A., Doka J.C., Romsa D.E. Acromegaly—use of fiberoptic laryngoscopy to avoid tracheostomy. Anesthesiology . 1981;54(5):429-430.
89. Young M.L., Hanson C.W.3rd. An alternative to tracheostomy following transsphenoidal hypophysectomy in a patient with acromegaly and sleep apnea. Anesth. Analg. . 1993;76(2):446-449.
90. Hakala P., Randell T., Valli H. Laryngoscopy and fibreoptic intubation in acromegalic patients. Br. J. Anaesth. . 1998;80(3):345-347.
91. Kristensen M.S. The Parker Flex-Tip tube versus a standard tube for fiberoptic orotracheal intubation: a randomized double-blind study (see comment). Anesthesiology . 2003;98(2):354-358.
92. Law-Koune J., Liu N., Szekely B., et al. Using the intubating Laryngeal Mask Airway for ventilation and endotracheal intubation in anesthetized and unparalyzed acromegalic patients. J. Neurosurg. Anesthesiol. . 2004;16(1):11-13.
93. Juvin P., Lavaut E., Dupont H., et al. Difficult tracheal intubation is more common in obese than in lean patients. Anesth. Analg. . 2003;97(2):595-600.
94. Lluch I., Ascaso J.F., Mora F., et al. Gastroesophageal reflux in diabetes mellitus. Am. J. Gastroenterol. . 1999;94(4):919-924.
95. Combes X., Leroux B., Jabre P., et al. Out-of-hospital rescue oxygenation and tracheal intubation with the intubating laryngeal mask airway in a morbidly obese patient. Ann. Emerg. Med. . 2004;43(1):140-141.
96. Araki K., Nomura R., Tsuchiya N., et al. Cardiovascular responses to endotracheal intubation with the Bullard and the Macintosh laryngoscopes. Can. J. Anaesth. . 2002;49(5):526.
97. Paul M., Dueck M., Kampe S., et al. Intracranial placement of a nasotracheal tube after transnasal trans-sphenoidal surgery. Br. J. Anaesth. . 2003;l 91(4):601-604.
98. Newfield P., Albin M.S., Chestnut J.S., et al. Air embolism during trans-sphenoidal pituitary operations. Neurosurgery . 1978;2(1):39-42.
99. Fleming J.A., Byck R., Barash P.G. Pharmacology and therapeutic applications of cocaine. Anesthesiology . 1990;73(3):518-531.
100. Kasemsuwan L., Griffiths M.V. Lignocaine with adrenaline: is it as effective as cocaine in rhinological practice? Clin. Otolaryngol. Allied. Sci. . 1996;21(2):127-129.
101. Horrigan R.W., Eger E.I., Wilson C. Epinephrine-induced arrhythmias during enflurane anesthesia in man: a nonlinear dose-response relationship and dose-dependent protection from lidocaine. Anesth. Analg. . 1978;57(5):547-550.
102. Abou-Madi M.N., Trop D., Barnes J. Aetiology and control of cardiovascular reactions during trans-sphenoidal resection of pituitary microadenomas. Can. Anaesth. Soc. J. . 1980;27(5):491-495.
103. Hill J.N., Gershon N.I., Gargiulo P.O. Total spinal blockade during local anesthesia of the nasal passages. Anesthesiology . 1983;59(2):144-146.
104. Todd M.M., Warner D.S., Sokoll M.D., et al. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide (see comment). Anesthesiology . 1993;78(6):1005-1020.
105. Gupta A., Stierer T., Zuckerman R., et al. Comparison of recovery profile after ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: a systematic review. Anesth. Analg. . 2004;98(3):632-641.
106. Gemma M., Tommasino C., Cozzi S., et al. Remifentanil provides hemodynamic stability and faster awakening time in transsphenoidal surgery. Anesth. Analg. . 2002;94(1):163-168.
107. Banoub M., Tetzlaff J.E., Schubert A. Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring. Anesthesiology . 2003;99(3):716-737.
108. Chacko A.G., Babu K.S., Chandy M.J. Value of visual evoked potential monitoring during trans-sphenoidal pituitary surgery. Br. J. Neurosurg. . 1996;10(3):275-278.
109. Fukushima T., Maroon J.C. Repair of carotid artery perforations during transsphenoidal surgery. Surg. Neurol. . 1998;50(2):174-177.
110. Britt R.H., Silverberg G.D., Prolo D.J., et al. Balloon catheter occlusion for cavernous carotid artery injury during transsphenoidal hypophysectomy. Case report. J. Neurosurg. . 1981;55(3):450-452.
111. Lee H.W., Caldwell J.E., Wilson C.B., et al. Venous bleeding during transsphenoidal surgery: its association with pre- and intraoperative factors and with cavernous sinus and central venous pressures. Anesth. Analg. . 1997;84(3):545-550.
112. Manninen P.H., Raman S.K., Boyle K., et al. Early postoperative complications following neurosurgical procedures. Can. J. Anaesth. . 1999;46(1):7-14.
113. Nemergut E.C., Zuo Z., Littlewood K.E., et al. Increased postoperative pain and vomiting in patients undergoing transsphenoidal surgery complicated by intraoperative CSF-leak. Anesthesiology . 2004;101:A370.
114. Apfel C.C., Korttila K., Abdalla M., et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N. Engl. J. Med. . 2004;350(24):2441-2451.
115. Jane J.A.Jr., Laws E.R.Jr. The surgical management of pituitary adenomas in a series of 3,093 patients. J. Am. Coll. Surg. . 2001;193(6):651-659.
116. Robertson G.L., Harris A. Clinical use of vasopressin analogues. Hosp. Pract. (Off. Ed.) . 1989;24(10):114-118. 126–128 133 passim
117. Seckl J., Dunger D. Postoperative diabetes insipidus. BMJ . 1989;298(6665):2-3.
118. Olson B.R., Gumowski J., Rubino D., et al. Pathophysiology of hyponatremia after transsphenoidal pituitary surgery. J. Neurosurg. . 1997;87(4):499-507.
119. Kelly D.F., Laws E.R.Jr., Fossett D. Delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Report of nine cases. J. Neurosurg. . 1995;83(2):363-367.
120. Oh M.S., Kim H.J., Carroll H.J. Recommendations for treatment of symptomatic hyponatremia. Nephron . 1995;70(2):143-150.
121. Reeder R.F., Harbaugh R.E. Administration of intravenous urea and normal saline for the treatment of hyponatremia in neurosurgical patients. J. Neurosurg. . 1989;70(2):201-206.
4 The Perioperative Care of the Pituitary Patient

Ian F. Dunn, Dilantha B. Ellegala, Mary Lee Vance, Edward R. Laws

The goals of definitive surgical treatment of pituitary lesions are the reversal of endocrinopathy and restoration of normal pituitary function; elimination of mass effect and restoration of normal neurological function; elimination or minimization of the possibility of tumor recurrence; and establishment of a definitive histological diagnosis. Just as important as the operative intervention, however, is the appropriate recognition and management of the variable clinical manifestations of lesions in this region before surgery along with attentive postoperative care.
In most centers today, patients with pituitary lesions are treated by a multidisciplinary team consisting of endocrinologists, neurosurgeons, and in select cases radiation oncologists. Nevertheless, despite the widespread consensus regarding the work-up and diagnosis of pituitary-related endocrinopathies and transsphenoidal surgical techniques, standardized perioperative management algorithms do not exist for pituitary tumors. The Pituitary Center at the University of Virginia (UVA) is one facility that has implemented a stringent standardized approach to managing patients with pituitary lesions. Thorough, comprehensive, and efficient evaluation of such patients and their surgical management and postoperative care are tasks shared by a multidisciplinary pituitary center staffed by a team of endocrinologists and neurosurgeons. In their original article, Laws et al stated that their goal in the management of pituitary patients was to “assure the safety of the patient, to avoid unnecessary discomfort and expense, and to achieve a normal endocrine state as rapidly as possible.” 1 We present the management of the pituitary patient as it is currently practiced in the hope of promulgating these goals, which remain as relevant today as they were in 1980.

Preoperative Evaluation: Establishing an Anatomical and Endocrinological Diagnosis and Managing Endocrinopathy

Anatomical Diagnosis
Central to the preoperative evaluation of patients in whom a pituitary tumor is suspected is an appropriate anatomical or radiological diagnosis and a thorough endocrinological work-up. Gadolinium-enhanced magnetic resonance imaging (MRI) has supplanted skull radiographs and computed tomography (CT) in establishing an anatomical diagnosis and is over 90% sensitive in the detection of microprolactinomas. 2 Fine-cut CT scans of the sella remain useful in cases of difficult re-operations in patients originally operated on elsewhere. Magnetic resonance imaging not only delineates the anatomy of mass lesions but also aids in the visualization of the relationship of tumor to the neighboring carotid arteries, optic chiasm, and to the parasellar region. MRI coupled with magnetic resonance angiography (MRA) may also confidently exclude the possibility that a sellar mass represents an aneurysm. Additionally, radiographical suggestion of craniopharyngioma or an infiltrative process—both of which are more likely to lead to panhypopituitarism and diabetes insipidus (DI) after their surgical resections—may make the neurosurgeon more vigilant as to alterations in endocrinological aberrations after surgery.
Although MRI establishes an anatomical diagnosis, the functional consequences of a lesion near the optic chiasm should also be investigated. Formal visual field testing should be performed and should certainly be done in patients with preoperative visual complaints or deficits. 3

Endocrinological Diagnosis
Knowledge of the particular subtype of pituitary lesion is important because lesions such as prolactinoma are best treated by medical means as first-line therapy. The pituitary endocrinology team performs the crucial preclinical evaluation before consideration of the patient for surgical management. The need for additional testing is ascertained before the patient’s visit to the clinic so that studies can be scheduled with the laboratory and with interventional radiology as indicated. Most commonly these additional tests involve high-dose dexamethasone suppression testing or inferior petrosal sinus sampling (IPSS). Other testing, such as a cardiac evaluation in the patient with acromegaly or oral glucose tolerance testing, can be arranged for the same day the patient is seen in the pituitary clinic. Extracranial imaging may be required in cases of suspected Cushing’s syndrome and acromegaly to exclude ectopic sources of endocrinopathy.
The routine preoperative laboratory workup consists of a complete blood count to assess for the presence of anemia or other hematological abnormalities, a metabolic panel to evaluate for the presence of hyponatremia, hypercalcemia, hyperglycemia, and other metabolic abnormalities. Cushing’s syndrome may produce abnormalities in the standard metabolic panel and blood count, such as hypokalemic metabolic alkalosis, hyperglycemia, and leukocytosis. The endocrinological evaluation involves measurement of pituitary and target gland hormones, including a thyroid panel (T4, TSH), cortisol, ACTH, IGF-1, testosterone, luteinizing hormone (LH)/ follicle-stimulating hormone (FSH), α-subunit, and prolactin (PRL). Laboratory evaluation is critical in patients with prolactin-secreting macroadenoma; in a macroadenoma (>1 cm), PRL should be greater than 200 μg/L to be considered a true prolactinoma, thereby indicating medical and not surgical therapy. 4 One should bear in mind that macroadenomas may have moderately elevated PRL because of interference with dopamine inhibition of lactotrope cells—the so-called “stalk effect.” Medical treatment options for other secretory tumors are listed in Table 4-1 . Serum calcium and glycated hemoglobin are also assessed to detect patients who may have MEN-I. If the patient is a surgical candidate and has no history of undue bleeding or risk factors for bleeding, a prothrombin time (PT)/partial thromboplastin time (PTT) is not typically obtained, but blood typing is performed.
Table 4-1 Principles of Pituitary Replacement Therapy Pituitary Insufficiency Replacement Therapy Cortisol Hydrocortisone or prednisone Thyroid Synthroid, Levoxyl Testosterone Testosterone injections, patch, or gel Estrogen Oral contraceptive, Prem/Pro ADH dDAVP Growth hormone Growth hormone
The particular type of secretory tumor has implications for preoperative management. Specifically, patients with TSH-secreting tumors, Cushing’s syndrome, and acromegaly necessitate particular attention paid to attendant extracranial medical problems arising in the setting of these endocrinopathies. Diagnostically, a low T4 and normal or suppressed thyroid-stimulating hormone (TSH) may suggest secondary hypothyroidism, whereas elevated T4 and normal or increased TSH indicates a TSH-producing tumor. Hyperthyroidism from a TSH-secreting tumor, although rare, requires treatment to reduce the risk of perioperative cardiac arrhythmias. 4
Patients with Cushing’s disease and acromegaly may warrant special attention secondary to the physiological effects of glucocorticoid or growth hormone excess. As many as 80% of patients with Cushing’s disease have systemic hypertension and 50% of untreated patients with Cushing’s disease have a diastolic blood pressure greater than 100 mm Hg. 5 As might be expected in patients with systemic hypertension, ECG abnormalities are common in patients with Cushing’s disease. High voltage QRS complexes and inverted T waves suggesting left ventricular hypertrophy and left ventricular strain have been described. 6 Obstructive sleep apnea (OSA) is also common among patients with Cushing’s disease. Glucose intolerance occurs in at least 60% of patients with Cushing’s disease, with overt diabetes mellitus present in up to one third of all patients. Nephrolithiasis is common in Cushing’s disease, with approximately 50% of active, untreated patients having detectable stones. 7
In patients with elevated cortisol and suspected Cushing’s syndrome, a 24-hour urinary free cortisol of more than 400 μg/day in a patient is diagnostic 8 ; these patients will also have an elevated midnight plasma cortisol, which under normal physiological conditions is at low levels. 9 The low-dose dexamethasone suppression test establishes the diagnosis of Cushing’s syndrome. Elevated corticotropin (>10 pg/mL) suggests a corticotropin-secreting tumor, while subnormal levels (<5 pg/mL) confirms a corticotropin-independent Cushing’s syndrome. 10 Dynamic testing is required to identify the source of hormonal excess in cases of elevated or normal corticotropin and elevated cortisol. 4 A high-dose dexamethasone suppression test assists in the determination of a pituitary or ectopic source of corticotropin.
Inferior petrosal sinus sampling (IPSS) for corticotropin after stimulation with Corticotropin Releasing Hormone (CRH), while invasive, is a reliable and accurate method of discerning pituitary from nonpituitary corticotropin-dependent Cushing’s syndrome. Although MRI and laboratory analysis have obviated the need for IPSS in most patients, it is a particularly useful discriminatory tool in concert with CRH administration in patients with classic clinical and laboratory Cushing’s disease but in whom MRI findings are negative or equivocal; equivocal results are obtained from suppression and stimulation tests; and in whom a compelling clinical presentation exists. A ratio of inferior petrosal sinus to peripheral ACTH of greater than 3.0 is diagnostic of central Cushing’s disease. 4 Eighty percent of Cushing’s syndrome patients have a pituitary adenoma and Cushing’s disease; 5% to 10% have an ectopic source of ACTH, such as carcinoid tumor; and a small fraction have cortical excess from an adrenal source. 11
Acromegaly is accompanied by skeletal and soft tissue overgrowth, deformities, and cardiac, respiratory, neuromuscular, endocrine, and metabolic complications. The cardiovascular and respiratory sequelae are particularly important to bear in mind in the care of the acromegalic patient. Atherosclerosis, hypertension, premature CAD, and arrhythmias leading to CHF may develop, and more than 20% of patients have cardiac disease at the time of diagnosis. 12 - 14 Indeed, the most frequent cause of death in untreated acromegaly is cardiovascular demise, with 50% of patients dying before the age of 50. Echocardiography may reveal an increase in left ventricular mass, stroke volume, cardiac output, or isovolemic relaxation time, all of which contribute to a poorly compliant left ventricle and the accompanying need for high filling pressures. 14 Given the potential for cardiac morbidity in acromegalic patients, a careful history and physical examination with close attention to the patient’s cardiac status should be routinely performed. Complaints consistent with congestive heart failure warrant preoperative cardiology consultation. Additional considerations include obstructive tissue thickening along the upper respiratory tract complicating intubation and possibly requiring an awake fiberoptic intubation. They may also be unable to tolerate nasal packing and have exacerbations of obstructive sleep apnea. Growth hormone excess causes insulin resistance in 20% to 30% of patients. 15 Preoperative laboratory testing in patients with acromegaly includes measurement of GH and IGF-1 as useful adjuncts in establishing a diagnosis but also includes the oral glucose tolerance test (OGTT), most useful in comparing preoperative and postoperative effects of glucose stimulation on growth hormone (GH) suppression. Overall, life expectancy is reduced by 10 years in acromegalic patients when compared with age-matched controls; reducing GH levels to less than 2.5 μg/L may normalize life expectancy. 16

Preoperative Management
The goals of surgical intervention remain the reversal of endocrinopathy, preservation/restoration of normal pituitary function, recovery of normal visual function, avoidance of diabetes insipidus or new hypopituitarism, tumor removal (cytoreduction), and collection of tissue for histological, immunocytochemical, ultrastructural, molecular biological, and molecular pathological study.
Appropriate hormone replacement is instituted after a thorough preoperative evaluation. Patients presenting with hypopituitarism are treated with cortisol and thyroid replacement as indicated ( Table 4-1 ). A regimen of 20 mg of hydrocortisone upon arising and 10 mg at 5 to 6 pm is initiated if the patient is hypocortisolemic and is begun at the time of initial evaluation. Thyroid hormone replacement is administered, beginning with a very small dose in patients who are elderly or who have coronary artery disease. Testosterone replacement is usually postponed until persistent hypogonadism is confirmed at the 6-week postoperative evaluation.
On the day of surgery, patients with hypocortisolemia and those who are receiving cortisol replacement therapy are given an intravenous dose of 100 mg of hydrocortisone in the preoperative holding area. Patients with Cushing’s disease are not given hydrocortisone perioperatively. We administer a 2 g preoperative dose of nafcillin IV barring penicillin allergy and continue an IV or oral antibiotic regimen postoperatively until the nasal dressing is removed. Our patients are now admitted routinely on the morning of surgery rather than the preceding evening.

Intraoperative Management
Anesthesia is conducted by a dedicated neuroanesthesiologist familiar with the particular cardiopulmonary physiology of acromegalic and Cushing’s patients. Patients with acromegaly display hypertrophy of the facial bones, especially the mandible. In addition, soft tissues of the nose, mouth, tongue, and lips become thicker. Thickening of the laryngeal and pharyngeal soft tissues leading to a reduction in the size of the glottic opening, hypertrophy of the periepiglottic folds, calcinosis of the larynx, and recurrent laryngeal nerve injury can all contribute to airway obstruction. Sleep apnea secondary to upper airway obstruction (OSA) can affect up to 70% of acromegalic patients. 17 If airway difficulty is anticipated, awake intubation is often employed.
No indwelling urinary catheter is used, as the average anesthesia time is less than 2½ hours. Patient positioning and the operative details have been published previously. 18 Of note, we use the ointment-lubricated cut fingers of surgical gloves loosely packed with gauze sponges as an inexpensive alternative to standard nasal packing material and, in addition, patients with acromegaly will have a nasal breathing “trumpet” placed to maintain a nasal airway after surgery.
A lumbar catheter is occasionally employed for the patient with a large suprasellar extension of tumor, particularly when the sella is not greatly enlarged. It is usually removed at the end of the operation, and its use is avoided in elderly patients.
When a CSF leak is identified at the time of surgery, abdominal fat is harvested and the sella is fat packed. If no occult CSF leakage is identified, then Gelfoam is placed in the sella and in both cases the floor is reconstructed with either bone or an absorbable plate.

Postoperative Management
Patients are transported from the operating room to the postoperative care unit (PACU) where they are closely monitored by nursing and anesthesia staff until they have recovered from the effects of anesthesia (usually 1 to 2 hours). Initial examinations to ascertain visual function and general neurological condition are performed by the pituitary neurosurgery resident in the PACU. The most common patient complaint after transsphenoidal surgery is a headache. Pain may be treated with narcotics, nonsteroidal drugs such as ketorolac, or acetaminophen. Nausea and vomiting is a very common postoperative complication in patients undergoing neurosurgical procedures, with nearly 40% of patients reporting some such complaint. 19 Given the high risk for vomiting in patients undergoing this procedure and the detrimental effect of vomiting on ICP, we routinely provide all patients with pharmacological prophylaxis.
Visual deterioration identified in the PACU is treated with an emergent return to the operating room for decompression of the optic chiasm if a mass lesion is suspected (hematoma, excess fat packing). If a mass lesion is not suspected, the patient is transported emergently for CT scanning with potential return to the operating suite for exploration.
Following adequate recovery in the PACU, patients are transferred to the neurosurgical/pituitary floor. Postoperative pituitary patients who undergo a transsphenoidal procedure are not ordinarily cared for in an ICU setting.
Once the patient is admitted to the neurosurgical inpatient ward, the nasal packing is removed in all patients who have undergone an uncomplicated approach. If the approach was difficult, the mucosa was particularly fragile or bloody, or the patient has Cushing’s disease with associated poor wound healing, the nasal packs will remain overnight and be removed on the first postoperative morning. Early removal of nasal packs markedly improves patient comfort and has not resulted in the need for repacking for excessive bleeding. If an abdominal fat graft was obtained, the dressing is removed on the second postoperative day and the site is inspected for postoperative hematoma or signs of infection.
If CSF rhinorrhea is observed after removal of nasal packing in patients who have not had fat packing, they are returned to the OR for fat packing. In those in whom fat packing has been performed, lumbar drainage is tried for a brief duration (2 to 3 days) and patients are taken back to the OR for repacking should lumbar drainage fail.
The postoperative patient, excluding the patient with Cushing’s disease, is given a regimen of 50 mg of intravenous hydrocortisone every 6 hours for four doses. Serum cortisol levels are obtained on the second and third postoperative days and replacement therapy is resumed only if hypocortisolemia is confirmed (6 am serum cortisol level <10 μg/dL). Such patients are converted to an oral replacement regimen of 20 mg of hydrocortisone every morning upon waking followed by 10 mg of hydrocortisone at 6 pm . This is tapered to a 15 mg/5 mg regimen at discharge as tolerated. Parenteral intravenous steroids are given if orally administered steroids are poorly tolerated.
Patients with Cushing’s disease have serum cortisol levels measured every 6 hours until symptoms of adrenal insufficiency develop. Upon confirmation of adrenal insufficiency (serum cortisol level less than 2), a single intravenous dose of hydrocortisone (50 mg) is administered followed by oral replacement, with the dose titrated to symptoms. Patients with Cushing’s disease are restricted to the immediate environs of the neurosurgical/pituitary floor until replacement therapy is initiated to preclude the onset of adrenal insufficiency and adrenal crisis while removed from neurosurgical care. Patients with Cushing’s disease have a higher risk for developing a postoperative pulmonary embolism, necessitating early postoperative mobilization.
Antibiotics are given intravenously and then orally when tolerated until the nasal packing is removed. We administer 2 g of nafcillin every 6 hours intravenously and then convert to dicloxacillin (500 mg PO q6h) when the patient is tolerating oral intake. Erythromycin or vancomycin may be used in patients with a penicillin allergy. Patients with Cushing’s disease have a higher incidence of deep venous thromboses and as such these patients receive prophylactic low dose aspirin (81 mg) therapy as soon as they are tolerating oral intake.
Laboratory testing in the postoperative period includes a daily chemistry and monitoring of the complete blood count. If hypernatremia is suspected, chemistry panels may be obtained more frequently along with serum and urine osmolality measurement. For patients with prolactinoma, a prolactin level is drawn on postoperative day 1 and 2. Patients with acromegaly have a growth hormone level and a prolactin level measured on postoperative days 1 and 2.
Urinalyses are collected for laboratory specific gravity testing—as opposed to dipstick testing—every 4 hours. Diabetes insipidus (DI) is most common in the first 2 days after surgery but rarely may follow a triphasic response wherein early DI is followed by a syndrome of inappropriate antidiuretic hormone secretion (SIADH)–like state about 5 days after surgery, after which a “prolonged” DI ensues. 20, 21 Diabetes insipidus is diagnosed by a combination of factors: urine output greater than 300 cc per hour for at least 3 hours and a urine specific gravity of 1.000, in concert with sodium greater than 150. Patients are permitted to drink ad libitum and are treated for DI with desmopressin (dDAVP) if unable to maintain adequate oral intake or if kept awake through the night. Patients with acromegaly often manifest a significant diuresis immediately after surgery and therefore we are more hesitant to treat a high urine output in these patients. Reliable daily patient weights using the same scale are an important adjunct in monitoring fluid balance.
Nursing care for the postoperative pituitary patient relies upon a core group of experienced senior staff who are “expert neurosurgery nurses.” These pituitary nurses work in 12-hour shifts, rather than shorter 8- or 10-hour shifts, to maintain continuity of care. Immediate postoperative nursing care begins with continuous noninvasive monitoring of blood pressure, heart rate, and oxygen saturation for the first 12 hours after surgery. This close observation is relaxed to every 2 hours for 24 hours and every 4 hours thereafter. Nasal saline sprays are given ad libitum for patient comfort. Antiemetics may be administered, particularly if the patient experiences an initial bout of emesis that occurs in the occasional patient who may have swallowed bloody drainage. It is essential at the end of the operation that the surgeon performs thorough suctioning of the patient’s nose, mouth, and pharynx while the patient is still intubated to minimize postoperative nausea and vomiting. Intake and output are initially measured every hour for the first 12 hours, followed by scrupulous recording of daily totals thereafter; an effort that is aided by the patient and family members.
In fact, a critical aspect of the postoperative care of pituitary patients is the recruitment of the patient and family members in their own care. Patient education begins with the preoperative clinic visit and progresses throughout the postoperative period. Education and enlistment of family members is conducted by the nursing staff upon arrival of the patient to the floor. Family members are allowed to stay in the patient’s room, and education about monitoring of the patient and precautionary education regarding diabetes insipidus and the symptoms of postoperative hyponatremia 6 are explained. As soon as the patient is able to assist in his or her care, he or she is included in this effort. By the first postoperative morning, the majority of patients are conducting self-assessment.
Discharge of patients after standard endonasal transsphenoidal surgery is occurring more quickly than even a year or two ago. The majority of patients are discharged home on either postoperative day 2 or 3. Earlier discharge is due to several factors. The endonasal approach is now conducted with a septal pushover technique that is less traumatic and is occasionally performed endoscopically. This allows for prompt removal of nasal packing and a quicker return of the patient to a more “normal” status. Patients are better informed during their hospitalization as to warning signs and symptoms of concern, and are therefore more comfortable with earlier discharge. Also, patients are reassured by the neurosurgical and endocrine services that are available 24 hours a day, affording a significant measure of security.
The current limiting factor in time to patient discharge is therefore the determination of the cortisol level on postoperative day 2. Patients with a cortisol level of less than 10 are discharged on a regimen of oral hydrocortisone replacement; all other patients are given a supply of hydrocortisone and are instructed to telephone the neurosurgery team should malaise, nausea, vomiting, or other symptoms of hypocortisolemia or hyponatremia occur. If a patient calls with such symptoms, he or she is instructed to obtain a serum cortisol and serum sodium level immediately and to telephone back with those results. Hydrocortisone may be given as a precaution after the blood sample is obtained pending the results.
Patients return to the pituitary clinic 6 weeks after surgery for follow-up evaluation. This includes laboratory testing to ascertain the possible need for adrenal steroid or thyroid replacement and gonadal function. The wound is inspected, during which time the nasal mucosa is inspected for perforations and patients are questioned regarding sinus complaints. If an abdominal fat graft was taken, the site is carefully inspected. Patients with successfully treated Cushing’s disease are instructed to discontinue hydrocortisone replacement at least 24 hours before the postoperative visit, at which time serum cortisol and ACTH levels are measured. An insulin hypoglycemia test (ITT) may be performed to assess recovery of the pituitary-adrenal axis and to diagnose growth hormone deficiency. Patients with acromegaly are prescheduled for an oral glucose tolerance test with growth hormone measurement the day of the postoperative visit.
Yearly laboratory tests of pituitary function are performed in all patients. A postoperative MRI scan is obtained 3 months postoperatively in all patients, and then yearly in most patients. If anatomical imaging or endocrine testing reveals recurrent or significant residual tumor, further treatment is planned (see Tables 4-2 and 4-3 ). It is vital that regular long-term follow-up is continued because these tumors may recur even as late as 20 years after initial treatment.
Table 4-2 Adjunctive Treatment for Persistent or Recurrent Tumors Adjunctive Measures for Treatment of Pituitary Tumors Conventional radiotherapy Fractionated radiotherapy (teletherapy) Stereotactic radiotherapy/radiosurgery
Linac-based (fractionated)
Linac-based (single fraction)
Gamma knife (single fraction)
Proton beam (single fraction or fractionated), Repeat surgery Transsphenoidal or craniotomy Chemotherapy Ineffective
Table 4-3 Medical Therapy for Hyperfunctioning Pituitary Tumors Hormone Produced By Tumor Medical Therapy Growth hormone
Somatostatin analog (octreotide)
Growth hormone receptor blocker Prolactin Dopamine agonist ACTH (Cushing’s disease) Ketoconazole to block cortisol synthesis TSH Somatostatin analog (octreotide)

Postoperative Management After Extended Transsphenoidal Surgery
The postoperative care of patients after extended transsphenoidal surgery 22 includes considerations specific to the complexity of this technique. The approach uses both a sublabial and endonasal dissection and nasal packing is maintained longer, usually until postoperative day 2. Lumbar drainage is continued after surgery until the nasal packs are removed, at which time the drain is clamped for 12 hours to assess for CSF leak before removal. Antibiotic prophylaxis is essential because the incidence of meningitis following the extended approach is significantly higher compared with the traditional approach. Typically patients are treated with a broad-spectrum antibiotic (ceftriaxone 2 g IV q12h) until the lumbar drain is removed.
A significant proportion of patients with lesions requiring an extended approach are hypocortisolemic before surgery; these patients thus typically require hydrocortisone replacement postoperatively as described previously. Assessment of visual function is critical; transient visual dysfunction as evidenced by central scotoma or visual field defect is occasionally seen after radical surgery using this approach and in our experience resolves during the first postoperative week.

This regimen of perioperative management in a unified, specialized setting exemplifies the concept of systems-based medical care. It requires the close cooperation of all specialists: neurosurgery, neuroanesthesiology, neuroendocrinology, neuropathology, neurophthalmology, and the pituitary nursing staff. Persistent or recurrent lesions are particularly challenging and require a center of excellence to offer the complete spectrum of conventional and adjunctive therapies ( Table 4-2 ). Development of a pituitary center with dedicated experts has contributed to improved care and outcomes for these patients with both intracranial and systemic components to their disease.


1 Laws E.R., Abboud C.F., Kern E.B. Perioperative management of patients with pituitary microadenoma. Neurosurgery . 1980;7:566-570.
2 Rand T., Kink E., Sator M., et al. MRI of microadenomas in patients with hyperprolactinaemia. Neuroradiology . 1996;38:744-746.
3 Molitch M.E. Disorders of prolactin secretion. Endocrinol. Metab. Clin. North Am. . 2001;30:585-609.
4 Vance M.L. Perioperative management of patients undergoing pituitary surgery. Endocrinol. Metab. Clin. North Am. . 2003;32:355-365.
5 Ross E.J., Marshall-Jones P., Friedman M. Cushing’s syndrome: diagnostic criteria. Q. J. Med. . 1966;35:149-192.
6 Sugihara N., Shimizu M., Kita Y., et al. Cardiac characteristics and postoperative courses in Cushing’s syndrome. Am. J. Cardiol. . 1992;69:1475-1480.
7 Faggiano A., Pivonello R., Melis D., et al. Nephrolithiasis in Cushing’s disease: prevalence, etiopathogenesis, and modification after disease cure. J. Clin. Endocrinol. Metab. . 2003;88:2076-2080.
8 Nieman L.K. Cushing’s syndrome. In: DeGroot L.J., Jameson J.L., editors. Endocrinology . fourth ed. Philadelphia: WB Saunders; 2001:1691-1715.
9 Gorges R., Knappe G., Gerl H., et al. Diagnosis of Cushing’s syndrome: re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group. J. Endocrinol. Invest. . 1999;22:241-249.
10 Findling J.W., Raff H. Diagnosis and differential diagnosis of Cushing’s syndrome. Endocrinol. Metab. Clin. North Am. . 2001;30:729-745.
11 Reitmeyer M., Vance M.L., Laws E.R.Jr. The neurosurgical management of Cushing’s disease. Mol. Cell. Endocrinol. . 2002;197:73-79.
12 Colao A., Cuocolo A., Marzullo P. Impact of patient’s age and disease duration on cardiac performance in acromegaly: a radionuclide angiography study. J. Clin. Endocrinol. Metab. . 1999;84:1518-1523.
13 Colao A., Marzullo P., Di Somma C., et al. Growth hormone and the heart. Clin. Endocrinol. . 2001;54:137-154.
14 Lopez-Velasco R., Escobar-Morreale H.F., Vega B., et al. Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension? J. Clin. Endocrinol. Metab. . 1997;82:1047-1053.
15 Quabbe H.J., Plockinger U. Metabolic aspects of acromegaly and its treatment. Metabolism . 1996;45:61-62.
16 Holdaway I.M., Rajasoorya C. Epidemiology of acromegaly. Pituitary . 1999;45:1-10.
17 Guilleminault C., van den Hoed J. Acromegaly and narcolepsy. Lancet . 1979;2:750-751.
18 Laws E.R.Jr., Thapar K. Pituitary surgery. Endocrinol. Metab. Clin. North Am. . 1999;28:119-131.
19 Manninen P.H., Raman S.K., Boyle K., et al. Early postoperative complications following neurosurgical procedures. Can. J. Anaesth. . 1999;46:7-14.
20 Kelly D.F., Laws E.R.Jr., Fossett D. Delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Report of nine cases. J. Neurosurg. . 1995;83:363-367.
21 Verbalis J.G., Robinson A.G., Moses A.M. Postoperative and post-traumatic diabetes insipidus. Front. Horm. Res. . 1985;13:247-265.
22 Kaptain G.J., Vincent D.A., Laws E.R.Jr. Transsphenoidal approaches for the extracapsular resection of midline suprasellar and anterior cranial base lesions. Neurosurgery . 2001;9:94-100.
5 The Neuro-Ophthalmology of Pituitary Tumors

Jorge C. Kattah

The main purpose of this chapter is to provide a practical review of the visual and oculomotor manifestations of pituitary tumors. The close anatomical relationship between the pituitary gland with the visual pathways and the cavernous sinuses explains the rather frequent occurrence of decreased vision, loss of peripheral visual field, diplopia, and a myriad of ocular complaints, which may announce the presence of a pituitary tumor. We will begin this chapter with relevant anatomical considerations, followed by description of common symptoms and signs associated with pituitary tumors. A detailed examination protocol, with review of different patterns of visual loss, visual field defects, and oculomotor abnormalities, will be provided. Correlation between neuro-ophthalmologic and imaging findings, discussion of the differential diagnosis, and visual outcome associated with different treatment modalities will be the concluding section.

Neuro-Anatomical Considerations
The optic chiasm is formed by the converging intracranial optic nerves and lies within the suprasellar cistern. When viewed in the sagittal plane, it is tilted forward at an angle of 45 degrees ( Figure 5-1 ). It measures 12 mm in width, 8 mm in the A-P diameter, and 4 mm in thickness. It lies about 10 mm above the pituitary gland and is separated from it by the diaphragma sellas, a reflection of the dura mater, which is penetrated only by the pituitary stalk. The position of the optic chiasm may vary in relation with the sella. In 15% of patients, it is located just above the tuberculum sellas (prefixed) and in 5% of patients it is located above the dorsum sellas (postfixed).

Figure 5-1 Sagittal 1 mm MRI of the sellar region. The optic chiasm is tilted 45 degrees within the suprasellar cistern ( arrows ). The most frequent anatomic position of the midchiasm is above the tuberculum sella as shown in this figure. An anterior or posterior position to this structure constitutes a prefixed or postfixed chiasm. Compressive lesions will therefore cause different field defects as a function of this anatomical variant.
At the chiasm, axons originating from retinal ganglion cells located in the nasal retina will decussate and adjoin uncrossed axons from the fellow eye to form the optic tract. The ratio of crossed-uncrossed fibers is 53% to 47%. For nearly one century, it was assumed that axons originating from inferonasal retina ganglion cells took a backward detour into the contralateral optic nerve (Wilbrand knee). 1 In recent elegant experiments, Horton demonstrated that the knee described by Wilbrand was the result of the technique used to demonstrate the anatomy of the decussating fibers rather than a normal anatomical structure. 2 The method used in the early 1900s involved monocular enucleation, which was performed to allow better definition of the “crossing fibers.” Using the same technique used by Wilbrand, Horton demonstrated in enucleated monkeys how crossing axons from the normal eye compressed the atrophic axons from the enucleated eye and formed a “loop,” which is not present in nonenucleated monkeys ( Figure 5-2 ).

Figure 5-2 Left panel showing a darkfield view of a normal primate optic chiasm with an absent Wilbrand knee. The images represent a radiotracer (L-2,3,4,5- 3 H) proline, administered by intravitreal injection in the left eye only. It stains myelin dark in contrast to the dark unstained right optic nerve. Right panel showing a darkfield view of the optic chiasm using the same labeling technique. The monkey had an enucleation of the right eye 4 weeks earlier with secondary wallerian degeneration. Note the normal fibers of the left optic nerve entering the proximal optic nerve.
(Reproduced with permission by Horton JC: Wilbrand’s knee of the primate optic chiasm is an artefact of monocular enucleation. Trans Am Ophthalmo Soc 1997; 95:579-609.)
The cavernous sinuses, which contain cranial nerves III, IV, and VI; V1 and V2; the internal carotid arteries; and the surrounding sympathetic fibers, form the lateral wall of the sella. The pituitary gland lies in between both cavernous sinuses.
The normal anatomy of the sellar region can be visualized with precision using multiplanar T1-weighted MRI scans ( Figure 5-3 ). In the coronal plane the chiasm has a dumbbell shape and lies within the suprasellar cistern. The intracranial optic nerves can be visualized anterior to the chiasm. The posterior chiasm is flanked superiorly by the third ventricle and inferiorly by the pituitary stalk. The pituitary gland lies flat in the coronal plane. In the sagittal plane, the tilted chiasm can be easily identified above the pituitary. The normal signal from the anterior pituitary is isointense to the brain and the posterior pituitary is hyperintense. In the axial plane, the converging optic nerves, chiasm, and optic tract can be identified. Following contrast administration, the pituitary gland, pituitary stalk, and cavernous sinuses enhance.

Figure 5-3 Coronal 1 mm, unenhanced T1 MRI sections of the chiasm. In the left panel the optic nerves are emerging from the optic canal to begin the decussation ( arrows ). Middle panel shows the midchiasm and right panel shows the optic tracts.
The relationship of the chiasm with the circle of Willis is of significant importance when considering ocular signs of pituitary tumors. The supraclinoid carotid arteries ascend lateral to the optic chiasm. The anterior communicating and anterior cerebral arteries are anterior and superior, and the posterior communicating and posterior cerebral arteries lie posterior and below. The principal arterial supply to the chiasm originates from an inferior anastomotic circle formed by the hypophyseal artery (branch of the internal carotid artery), and branches from the posterior cerebral and posterior communicating arteries, which supply the main body of the chiasm and a superior anastomotic group that originates from the anterior cerebral arteries, which supply both the main body and lateral chiasm. Venous drainage is formed primarily by the pituitary portal system, which drains into the cavernous and petrosal sinuses.

Symptoms and Signs
The main symptoms and signs of pituitary tumors may be classified as endocrine, visual, oculomotor, and headache. This chapter will deal only with the neuro-ophthalmological manifestations and headache. Broadly speaking, the symptoms observed are the result of the relationship of the tumor with the displaced neighboring structures. Pituitary microadenomas cause primarily endocrine symptoms. Macroadenomas frequently cause compression of the chiasm and less commonly of the optic nerves or the optic tracts. The mass effect exerted by the tumor affects the axoplasmic flow and impairs vascular supply. If compression is exerted over a long period of time, functional recovery after decompression is significant. Abrupt compression, on the other hand, has a greater risk of suboptimal visual recovery.
1. Visual symptoms: Slowly progressive loss of vision affecting one or both eyes is a frequent complaint. At times visual loss is acute in nature. Not infrequently, patients become aware of poor vision in one eye only when closing the fellow eye, and are unable to date the precise onset of symptoms. Monocular or binocular decreased brightness and poor color perception may be present as well. Loss of peripheral visual field may be reported. Given the slow growing rate of pituitary adenomas, it is not infrequent to find “silent visual deficits” among patients with macroadenomas; therefore, it is important to perform a careful neuro-ophthalmological examination in all patients with pituitary tumors.
2. Oculomotor symptoms: Patients with lateral extension of pituitary tumors report diplopia and ptosis. These symptoms may be isolated or concurrent with visual loss and are typically slowly progressive as well.
3. Headache: Large pituitary tumors exert a mass effect on the diaphragma sellas and the cavernous sinus. They lead to dural stretching in the first instance and ophthalmic nerve compression in the second. However, headache may also occur in the absence of overt compression of these structures and is probably the result of endocrine abnormalities interacting with an underlying migraine background. 3 Patients with pituitary apoplexy may describe explosive headache and neck pain. We will discuss this syndrome in greater detail in this chapter.

Signs of Pituitary Adenomas: Visual Signs

1. Visual acuity : Patients with pituitary adenomas may report poor vision. Decreased visual acuity in one or both eyes is frequently found on examination. When binocular visual loss is present, it is often asymmetric.
2. Color vision : Poor monocular or binocular discrimination of red-green color, using the Ishihara or pseudoisochromatic plates, is often found among patients with pituitary adenomas. Bedside visual field testing, using a confrontation method with two red targets, may detect temporal-field red color desaturation. This is a valuable and specific sign, pointing to a chiasmal localization.
3. Pupils : Examination of the pupils is of great value in patients with pituitary tumors. Anisocoria may occur in association with sympathetic and parasympathetic failure. The reaction to light may be impaired in one or both eyes. An afferent pupillary defect (APD) is relatively uncommon, despite the fact that visual acuity or field loss is frequently asymmetric. The reaction to light may be impaired as a result of partial or complete third nerve palsy (loss of efferent, parasympathetic function). In this case, the size of the pupil is in the 4 to 5 mm range, contrasting with the 8 mm size pupils seen with lesions affecting the third nerve in other locations in the neuraxis.
4. Visual fields : A temporal visual field defect is a highly specific and sensitive sign of chiasmal localization. This observation also applies to monocular defects. Visual fields may be tested by confrontation. At times, bitemporal desaturation of red color may be found. Automated perimetry is of great value in patients with pituitary tumors. Since it is time-consuming, a normal attention span is required. This is generally the case in patients with pituitary tumors. Goldman, kinetic perimetry may be more suitable in uncooperative, ill patients.
Computerized visual field (CVF) testing is of great value in patients with pituitary tumors. Over the last 2 decades, CVF testing has emerged as the preferred modality of testing the peripheral visual field. The Humphrey and the Octopus units are the best known at this time. Both of them provide a standardized, reproducible, and sensitive test of peripheral vision.
A simplified explanation of CVF involves testing of the subject’s response to targets in different visual field locations while fixating at a central target. The main principle in static automated perimetry involves an evaluation of visual perception of stationary objects of constant size and changing intensity in different locations that are displayed at “threshold intensity” values at a given location tested. A threshold is defined as the stimulus intensity that has a 50% probability of being seen.
The computer algorithm used in CVF measures the differential light sensitivity between the stimuli used against a constantly illuminated background. The programs allow display of the patient’s response in numeric and graytone format plots of the raw threshold data ( Figure 5-4 ). It provides a reliability index of fixation losses, and false-positive and false-negative responses. CVF has several programs, among them a program known as Statpac provides additional critical information. Statpac shows a comparison of the patient’s response with age-matched normal values at each location (total deviation) and mean deviation , which is a location-weighted mean of the values found in the total deviation plot. More localized abnormalities are also plotted in the pattern deviation plot. We recommend the use of automated perimetry whenever possible in patients with pituitary tumors.
5. Visual fields syndromes: Topographically, one may classify the visual field abnormalities seen with lesions affecting the chiasm in three different syndromes: Anterior chiasmal syndrome or junction scotoma, midchiasm syndrome, and posterior chiasm. Pertaining to the junction scotoma, which may be defined as a central scotoma in one eye and a monocular temporal defect in the fellow eye ( Figure 5-5 ). As already mentioned, it is not usually seen with discrete lesions placed anterior to the chiasm, but usually occurs with rather large adenomas. 2 The midchiasm syndrome is characterized by a typical bitemporal superior quadrantopsia ( Figure 5-6 ); however, one may see at times unilateral temporal visual field defects with large sellar lesions. The macular fibers cross posterior in the chiasm, and bitemporal central scotomas may also be found. In patients with a prefixed optic chiasm, an incongruous homonymous visual field defect, due to optic tract compression, may be seen. This abnormal field is characterized by a nasal defect in one eye and a temporal defect in the fellow eye of markedly different shape ( Figure 5-7 ).

Figure 5-4 Visual fields plotted with a Humphrey automated perimeter. Observe in the left panel, the left visual field. Note reliability indices in the left upper corner: fixation losses, false-positive and false-negative responses. Notice the numeric scale and the gray tone scale. Observe mean deviation values and the total and pattern deviation plots. In the temporal field notice the presence of the physiological blind spot ( arrow ). In the right panel, note the same visual parameters described for the left eye.

Figure 5-5 Visual fields plotted with a Humphrey automated perimeter. Observe an asymmetric, bitemporal visual field defect, due to a pituitary tumor with a larger right sided expansion with greater compression of left nasal crossing fibers.

Figure 5-6 Visual fields plotted with a Goldman kinetic perimeter. Observe in the left panel a dense left temporal hemianopsia. In the right panel, there is a right superior temporal hemianopsia. A mild degree of interocular visual field defect asymmetry, which may be found frequently. The lesion responsible was a tuberculum sellas meningioma with chiasmal compression.

Figure 5-7 Visual fields plotted with a Goldman kinetic perimeter. It shows in the left eye an incomplete temporal field defect ( left ) and in the right eye, an incomplete nasal visual field defect ( right ). These findings represent a left homonymous hemianopic visual field defect. When superimposed, the contours of the defect in each eye do not match precisely (incongruous). This is a localizing abnormality to the optic tract. In this case it was the result of compression by a large eosinophilic adenoma compressing the right optic tract.


1. Oculomotor examination: Patients with pituitary tumors may have an ophthalmoparesis or ophthalmoplegia and may complain of diplopia. Isolated compromise of cranial nerves III and VI may occur. Frequently both nerves may be involved simultaneously. Whereas gradual onset is the rule, abrupt onset may also be present and suggests a diagnosis of pituitary apoplexy. Involvement of the trigeminal nerve may result in a painful ophthalmoplegia. Simultaneous chiasmal compression and oculomotor paralysis may be seen.
Paresis of the lateral rectus muscle due to cranial nerve VI compression in the setting of a pituitary tumor lacks a specific localizing value, unless a temporal visual field defect is found as well. On the other hand, third nerve paresis may well be localizing to the cavernous sinus. The size of the pupil in the paretic side is usually 4 to 5 mm, unlike the fully dilated pupil seen with third nerve palsies in other locations. Simultaneous compromise of the sympathetic and parasympathetic fibers accounts for the midsized pupil. The light reaction is either poor or absent and the pupil fails to dilate in the dark. Isolated compromise of cranial nerve IV would be exceptional in the setting of pituitary adenomas. A combination of unilateral, paretic extraocular muscles innervated by more than one cranial nerve is a frequent finding observed in patients with pituitary tumors ( Figure 5-8 ).

Figure 5-8 In the left panel, observe a young male with an acute, severely painful, partial right third nerve palsy. Note ptosis of the right upper eyelid and paralysis of the right medial rectus in left gaze. The pupil not seen in the picture was 5 mm and reacted poorly to light. In the right panel, a contrast-enhanced T1 coronal MRI shows rightward lateral extension of a sellar mass compressing the cavernous sinus. The patient had significant hyperprolactinemia and was treated with dopamine-agonist therapy with full resolution of all symptoms in the ensuing 8 weeks.
In the absence of the obvious limitation of ocular ductions (monocular eye movements), the use of the alternate cover test in search of a mild phoria or the red glass test will provide greater sensitivity if the patient is cooperative. A discussion of these techniques is beyond the scope of this chapter and may be found in general neuro-ophthalmology textbooks. 4
Patients with complete bitemporal hemianopsia and residual vision limited to both nasal fields experience primary gaze sensory diplopia as a result of the fact that the images seen in each eye (nasal field only) do not overlap and there is a vertical slide perception. This occurs in the absence of any oculomotor abnormality.
2. Ophthalmoscopic examination: The ophthalmoscopic examination may be performed with the direct ophthalmoscope. Unless the patient is lethargic, the pupil may be dilated with 1% tropicamide. With the use of these drops, the pupil dilates to about 6 mm within minutes and returns to a normal size in about 2 to 3 hours.
The optic nerve may be normal; however, pituitary tumors are generally slow-growing and the compression of the chiasm is exerted over months and years. Therefore, changes in the optic nerve head and the nerve fiber layer may be conspicuous. Compression of the crossing nasal fibers at the chiasm causes wallerian degenerations of axons with localized optic nerve bowtie atrophy. The nerve fiber layer may also be depleted of axons. This finding may be observed with a direct ophthalmoscope using the red free light. Significant chiasmal compression may cause diffuse unilateral or bilateral optic atrophy. Papilledema is extremely uncommon among patients with pituitary tumors, but may rarely be seen in pituitary apoplexy.
3. Biomicroscopic examination : The examination of the anterior segment of the eye is normal among patients with pituitary tumors. At times the pupil reaction to light can be examined with more precision when the standard penlight response is unclear. Patients with Cushing’s syndrome may have posterior subcapsular cataracts.
4. Ancillary tests to be performed upon completion of the examination: An algorithm for the workup of patients who have visual symptoms or headache and have clinical findings suggestive of pituitary tumors is proposed. Thin section, multiplanar MRI testing of the sellas, including baseline noncontrast scans, followed by postgadolinium scans should be obtained. The results may then be correlated with the visual fields. Pituitary tumors may abut the chiasm without disabling compression; therefore, it is often difficult to predict on the basis of imaging if visual pathway dysfunction would be present.

Differential Diagnosis

1. Intrinsic Chiasmal Lesions
Intrinsic lesions of the optic chiasm include demyelinating-inflammatory and granulomatous lesions, benign and malignant gliomas, and other less common tumors. Vasculitis and vascular malformations are uncommon.
a. Demyelinating-granulomatous-infectious: Chiasmal neuritis associated with MS and less frequently with acute disseminated encephalomyelitis (ADEM) is uncommon. Temporal visual field defects were present in 9% of patients reported in the optic neuritis treatment trial. 5 - 7 Unitemporal or bitemporal visual field defects may be found in these patients and the MRI excludes the possibility of a neoplasm and shows swelling of the chiasm with contrast enhancement (after the administration of gadolinium) caused by an acute breakdown of the blood-brain barrier (see Figure 5-5 ). Diffuse granulomatous and infectious lesions may also be seen, but more frequently they are tumefactive (sarcoidosis, histiocytosis, tuberculosis, cysticercosis, etc.). Nonspecific pachymeningitis and arachnoiditis may also be included.
b. Neurotoxicity: An unusual presentation among patients on ethambutol for treatment of tuberculosis is the occurrence of bitemporal visual field defects. 8
c. Chiasmal neoplasms: Primary optic nerve chiasmal gliomas may be frequently seen among patients with neurofibromatosis type I (NF-1). These tumors are indolent lesions, which may progress over a prolonged period of time and do not require immediate therapeutic intervention. 9 Detecting clinical signs or genetic evidence of NF-1 can make the diagnosis. Primary chiasmal glioblastomas are unusual lesions with very poor prognosis. 10 Other intrinsic tumors of the chiasm may also be present. 11, 12 Rarely, metastatic lesions can compress or infiltrate the chiasm and cause bilateral blindness. 13
d. Vascular malformations: Intrinsic vascular lesions : Chiasmal cavernous and venous angiomas, occasionally associated with chiasmal apoplexy, may be occasionally seen. 14 - 19 Involvement of the chiasm by vasculitis (giant cell arteritis) and other vasculitis while possible is rather uncommon.
Aneurysms and ectatic arteries : A large aneurysm originating in arteries in the circle of Willis may cause compression of the optic chiasm. In some instances the aneurysm has undergone spontaneous clotting and behaves primarily as a mass. Dolichoectatic carotid and other arteries in the circle of Willis may infrequently compress the optic chiasm.
2. Sellar Lesions
Patients with chiasmal field defects may have other neoplastic sellar masses that are not pituitary tumors.
a. Neoplastic: Meningiomas originating in the tuberculum sella, craniopharyngiomas, Rathke pouch cysts, germinomas, plasmocytomas, lymphomas, and metastatic lesions are the most common in the differential diagnosis.
b. Granulomatous lesions: The same lesions that may infiltrate the optic chiasm itself can also present as sellar masses with secondary compression. Sarcoidosis, tuberculosis, and cysticercosis are among the most common. Lymphocytic hypophysitis is an intriguing, presumably autoimmune, postpartum process that may occur with a pseudotumoral chiasmal syndrome. 20 An idiopathic granulomatous process affecting the infundibulum has been reported. 21 Sphenoidal sinus mucoceles may rarely erode the floor of the sellas and have a bitemporal visual field loss or ophthalmoplegia. 22
Pituitary adenocarcinomas are treatment-resistant pituitary tumors locally invasive that may rarely be complicated with metastases. 23
3. Suprasellar Masses
Neoplasms: The most common suprasellar tumor, which frequently compresses the chiasm and optic tract from above is the craniopharyngioma. 24, 25 Additional tumors in this region include the Rathke pouch and dermoid cysts, germinomas, teratomas, hypothalamic gliomas, meningiomas, plasmocytomas, lymphoma, leukemia, and metastatic lesions.
Granulomas: Sarcoidosis, tuberculosis, cysticercosis, hydatid cysts, etc. Large suprasellar subarachnoid cysts may be an unusual cause of a chiasmal syndrome.
4. Lateral Sellar Masses
The differential diagnosis of sellar mass lesions includes cavernous sinus meningiomas, aneurysms, schwannomas, metastatic lesions, including nasopharyngeal carcinoma. Inflammatory-granulomatous lesions, such as sarcoidosis, the Tolosa-Hunt syndrome, and other less common lesions must be considered. 26

We will discuss only those aspects of treatment that are relevant to the ocular manifestations of pituitary tumors. The majority of prolactinoma patients experience visual improvement with dopaminergic therapy (bromocriptine-cabergoline, etc.). Both chiasmal and cavernous sinus compression improve. 27, 28 Life-long therapy may be required. Dopaminergic therapy is therefore indicated as the front-line treatment, even in patients with macroprolactinomas exerting compression on the visual pathways or the cavernous sinuses. 27, 28
Visual improvement after transsphenoidal surgery is the rule. 29 It usually occurs within days and even hours after chiasmal decompression, and in rare instances, the surgical packing used to seal the sellar floor may act as a mass and compress the optic chiasm. 30 Herniation of the optic chiasm within the sella after resection of a pituitary tumor is not an uncommon imaging finding; however, only rarely it results in visual loss. 31 This complication may also occur with dopaminergic therapy.
Pituitary apoplexy: The clinical manifestations of pituitary apoplexy are quite varied. Advances in imaging techniques have shown that small hemorrhages within pituitary adenomas are quite common. In many instances patients complain of a mild headache with or without visual symptoms. Massive hemorrhage, on the other hand, occurs infrequently and has sudden onset of severe headache (95%), vomiting (69%), ocular paresis (78%), visual field defects (64%), and reduced visual acuity in 52% of cases. 32 Third nerve palsies are common. Altered level of consciousness because of hypothalamic compression or acute panhypopituitarism and meningeal irritation signs may be present as well. Most patients who have pituitary apoplexy are previously unaware that they harbored a pituitary adenoma. Trauma, anticoagulation, and other factors may precipitate hemorrhage in a patient with a pituitary tumor. Sudden increment of intranasal pressure may also be a factor leading to hemorrhage. Rapid decompression of the chiasm and correction of the neuroendocrine abnormalities should be accomplished without delay.
Residual pituitary tumor after surgical resection is generally treated with postsurgical irradiation. More precise delivery of irradiation has lessened the risk of postradiation necrosis of the chiasm and optic nerves, which could potentially lead to irreversible visual loss. 33 Close ophthalmological monitoring of patients with residual tumor is as important as the result of serial imaging. The functional effect of a residual mass on the chiasm is precisely measured by sequential examination and may be best detected with automated visual fields, which are compared with previous baseline studies. The proper management of pituitary tumors involves a team approach that encompasses sensitive and expeditious endocrine, ophthalmological, and imaging evaluations, leading to the selection of pharmacological and surgical treatment tailored to the specifics of the lesion to ensure the best treatment outcome.


1. Wilbrand H., Saenger A. Bergamann J., editor. Die Neurologie des Auges, vol. 3. 1904, Weisbaden, Germany: 98-120 (part 1)
2. Horton J.C. Wilbrand’s knee of the primate optic chiasm is an artefact of monocular enucleation. Trans. Am. Ophthalmol. Soc. . 1997;95:579-609.
3. Levy M.J., Jager R., Powell M., et al. Pituitary volume and headache. Arch. Neurol. . 2004;61:721-725.
4. G.T. Liu, Volpe N.J., Galetta S.L. Neuro-ophthalmology: Diagnosis and Management. Philadelphia: WB Saunders, 2001;3-40.
5. Optic Neuritis Study Group. The clinical profile of optic neuritis. Experience of the optic neuritis treatment trial. Arch. Ophthalmol. . 1991;109:1673-1678.
6. Keltner J.L., Johnson C.A., Spurr J.O., et al. Baseline visual field profile of optic neuritis. The experience of the optic neuritis treatment trial. Optic neuritis study group. Arch. Ophthalmol. . 1993;111:231-234.
7. Newman N.J., Lessell S., Winterkorn J.M. Optic chiasmal neuritis. Neurology . 1991;41:1203-1210.
8. Leibold J.E. The ocular toxicity of ethambutol and its relation with dose. N. Y. Acad. Sci. . 1966;135:904-909.
9. Listernik A.L., Louis D.N., Packer R.J., et al. Optic pathway gliomas in children with neurofibromatosis I: consensus statement from the NF1. Optic pathway glioma task force. Ann. Neurol. . 1997;41:143-149.
10. Hoyt W.F., Meshel L.G., Lesell S., et al. Malignant optic glioma of adulthood. Brain . 1973;96:121-132.
11. Duff T.A., Levine R. Intrachiasmatic craniopharyngioma. Case report. J. Neurosurg., 59, 1983: 176-178
12. Brodsky M.C., Hoyt W.F., Barnwell S.L., et al. Intrachiasmatic craniopharyngioma: a rare cause of chiasmal thickening. Case report. J. Neurosurg., 68, 1988: 300-302
13. Kattah J., Silgals R.M., Manz H., et al. Presentation and management of parasellar and suprasellar metastatic mass lesions. J. Neurol. Neurosurg. Psychiatry . 1985;48:44-49.
14. Maitland C.J., Abiko S., Hoyt W.F., et al. Chiasm apoplexy: report of four cases. J. Neurosurg. . 1982;56:118-122.
15. Hwang J.F., Yau C.W., Huang J.K., et al. Apoplectic optochiasmal syndrome due to intrinsic cavernous hemangioma. Case report. J. Clin. Neuroophthalmol., 13, 1993: 232-236
16. Kupersmith M.J. Vascular malformation of the brain. In: Neurovascular Neuro-ophthalmology . Berlin: Springer-Verlag; 1993:301-351.
17. Warmer J.E.A., Rizzo J.F., Brown E.W., et al. Recurrent chiasmal apoplexy due to cavernous malformation. J. Neuroophthalmol. . 1996;16:99-106.
18. Fermaglich J., Kattah J.C., Manz H. Venous angioma of the optic chiasm. Ann. Neurol. . 1978;4:470-471.
19. Corboy J.R., Galetta S.L. Familial cavernous angiomas manifesting with an acute chiasmal syndrome. Am. J. Ophthalmol. . 1989;108:245-250.
20. Levine S.N., Benzel E.C., Fowler M.R., et al. Lymphocytic hypophysitis: clinical, radiological and magnetic imaging characterization. Neurosurgery . 1988;22:937-941.
21. Case records of the Massachusetts General Hospital. N. Engl. J. Med. . 1985;312:297-305.
22. Goodwin J.A., Glaser J.S. Chiasmal syndrome in sphenoid sinus mucocele. Ann. Neurol. . 1978;4:440-444.
23. Atienza D.M., Vigersky R.J., Lack E.E., et al. Prolactin-producing pituitary carcinoma with pulmonary metastasis. Cancer . 1991;68:1605-1610.
24. Crane T.B., Yee R.D., Hepler R.S., et al. Clinical manifestations and radiologic findings in craniopharyngiomas in adults. Am. J. Ophthalmol. . 1982;94:220-228.
25. Sandford R.A., Muhlbauer M.S. Craniopharyngiomas in children. Neurol. Clin. . 1991;9:453-465.
26. Keane J.R. Cavernous sinus syndrome. Analysis of 151 cases. Arch. Neurol. . 1996;53:967-971.
27. Serri O. Progress in the management of hyperprolactinemia (editorial). N. Engl. J. Med. . 1994;331:942-944.
28. Talkad A., Kattah J.C., Xu M.Y., et al. Prolactinoma presenting as painful postganglionic Horner syndrome. Neurology . 2004;62:1440-1441.
29. Trautmann J.C., Laws E.R. Visual status after transsphenoidal surgery at the Mayo Clinic, 1971–1982. Am. J. Ophthalmol. . 1983;96:200-208.
30. Slavin M., Lam B.L., Decker R.E., et al. Chiasmal compression from fat packing after transsphenoidal resection of intrasellar tumor in two patients. Am. J. Ophthalmol. . 1993;115:368-371.
31. Czech T., Wolfsberger S., Reitner A., et al. Delayed visual deterioration after surgery for pituitary adenoma. Acta Neurochir. . 1999;141:45-51.
32. Bills D.C., Meyer F.B., Laws E.R., et al. A retrospective analysis of pituitary apoplexy. Neurosurgery . 1993;33:602-608.
33. Van der Bergh A., Schoorl M.A., Dullart R.P.F., et al. Lack of radiation optic neuropathy in 72 patients treated for pituitary adenoma. J. Neuroophthalmol. . 2004;24:200-205.
6 Rhinological Evaluation

Stephen S. Park, Daniel G. Becker

The approach to tumors of the pituitary gland has undergone a developmental evolution during the past century. While Sir Victor Horsley performed the first transcranial approach to the pituitary in 1899, 1 the Viennese surgeon Herman Schloffer introduced the transnasal transsphenoidal approach to the pituitary gland in 1907. 2 Historically significant modifications to this transsphenoidal approach include the sublabial incision proposed by Harvey Cushing’s in 1910, 3 fluoroscopical guidance introduced by Gerard Guiot in 1958, 4 the operating microscope demonstrated by Jules Hardy in 1965, 5 and most recently the use of endoscopes as a less invasive alternative. 6, 7 Through this evolving surgical technique, it remains imperative that the neurosurgeon have a working familiarity with the nasal anatomy, its variances, and preoperative evaluation.

Nasal Anatomy

The Sphenoid Sinus
The pituitary gland resides in the sella turcica whose floor is surrounded by the body of the sphenoid bone. The sella is defined anteriorly by its lip—the tuberculum sella—and posteriorly by the dorsum sella. In one series of cadaveric dissections, the sella was found to measure, on average, 8.5 mm in depth, 10 mm in length, and 13.5 mm in width, with a volume of 575 mm 3 . Moreover, in the majority of cases, the sella floor is less than 1 mm thick. 8 This sella floor corresponds to the posterior aspect of the roof of the sphenoid sinus. It is this relationship between the floor of the sella and the roof of the sphenoid sinus that makes the transsphenoidal approach to the pituitary gland feasible.
The sphenoid sinus aerates the sphenoid bone and is the posterosuperior limit between the nasal cavity and the middle cranial fossa ( Figure 6-1 ). Sphenoid pneumatization begins around 10 months of age with a period of significant enlargement between 3 and 6 years of age. Recent data demonstrate that the sinus continues to pneumatize through the third decade of life, extending to the dorsum sella with an average maximum volume of 8 cc. 9, 10 Pneumatization of the sphenoid sinus has been classified by Hamberger based on its extent of aeration as either sellar, presellar, or conchal. 11 In the sellar type, representing 73% to 86% of sphenoid sinuses, pneumatization extends fully into the body of the sphenoid and below the sella. In the presellar type, representing 11% to 27% of sphenoid sinuses, pneumatization does not extend past a plane perpendicular to the anterior sellar wall. In the conchal type, which represents 1% to 3% of sphenoid sinuses, there exists no pneumatization in the sphenoid bone. 12 Variances in this normal anatomy have obvious implications in terms of transsphenoidal approaches to the pituitary gland.

Figure 6-1 Skeletal structures of the lateral wall of the nose. The sphenoid sinus aerates the sphenoid bone and is the posterosuperior limit between the nasal cavity and the middle cranial fossa above. Also depicted are the superior, middle, and inferior turbinate bones. A supreme (fourth) turbinate bone, present in some patients, is not seen in this drawing.
(Drawing reproduced with permission of Marks S: Nasal and sinus surgery. WB Saunders, Philadelphia, 2000, p 11.)
The sphenoid sinus is usually divided into at least two asymmetrical cavities by a sagittally oriented intersinus septum, and in the majority of cases is also accompanied by accessory septas which may be oriented in any direction. A recent cadaveric study demonstrated that this intersinus septum terminates on the bulge of the internal carotid artery in 12% to 40% of cases, and on the optical canal in 5% to 7% of cases. 13, 14 Approximately one quarter of sphenoid sinuses have no intersinus septum 15 and exist as a single undivided cavity. Preoperative study of the sphenoid septae must be accomplished radiographically to anticipate these deviations and to distinguish between a sinus septum versus posterior or lateral sphenoid wall.
The lateral wall of the sphenoid sinus is adjacent to the cavernous sinus. Located medially within the cavernous sinus, and abutting the sphenoid sinus, the internal carotid artery may be appreciated on the endonasal view residing in its carotid sulcus and indenting the lateral wall of the sphenoid sinus. This bony carotid sulcus is dehiscent in as many as 22% of cases. 16 On endoscopic view into the sphenoid sinus, the optical nerve can be seen indenting the superolateral aspect of the sinus wall. As with the carotid artery, the bony covering of the optic nerve may be thin or dehiscent, although this occurs less frequently than with the carotid artery. How well the carotid artery and optic nerve are appreciated on the endonasal view into the sphenoid sinus is, in large part, because of the degree of sinus pneumatization as described by the Hamberger classification.
The sphenoid sinus drains via a natural ostium, which is located 1 cm superior to the posteroinferior end of the superior turbinate, and corresponds to the vertical middle of the anterior wall of the sphenoid sinus. 17 This ostium usually drains medially into the sphenoethmoidal recess and less frequently through the superior turbinate into the posterior ethmoid sinus. This ostium is located on average 56 mm from the limen nasi at a 36-degree horizontal angle, or 63 mm from the cutaneous nasal sill at a 34-degree angle. Several studies have shown that the posteroinferior end of the superior turbinate is the most reliable endonasal landmark for identification of the natural ostium of the sphenoid sinus. 18, 19

The External Nose
Transnasal approaches to the pituitary gland can be impacted by the external appearance of the nose, and a solid understanding of its supporting anatomy is important. The skin of the nose is often overlooked but can have an influence on nasal support. The upper half of the nasal skin is typically very thin and quickly reveals any structural irregularities that may be created from surgery. The skin of the nasal tip, on the other hand, tends to be much thicker and sebaceous, occasionally causing tip ptosis and nasal obstruction. The overall size of the nose can also be quite variable and impact the decision making in terms of route of access. Acromegalics, for example, have large noses that lend themselves well to any transnasal approach. Asian noses, on the other hand, tend to be smaller and may limit this approach. The congenitally small nose, traumatized nose, or twisted nose, all represent variations that should be part of the preoperative nasal evaluation.

Nasal Framework
The upper third of the nose consists of a pyramid of paired nasal bones, which articulate with the frontal bone at the nasofrontal suture. The soft tissue depression defines the nasion of the nose and creates the nasofrontal angle. Inferiorly, the nasal bones articulate with and support the superior border of the upper lateral cartilages. In the midline, it defines the rhinion and is the transition point to the middle nasal vault. It is in this area that most dorsal nasal humps occur.
Support for the middle one third of the nose is provided primarily by the dorsal septum and the upper lateral cartilages. The articulation between the upper lateral cartilages and the dorsal nasal septum has functional significance. Intranasally, these structures define the internal nasal valve , an important anatomical site for maintaining the laminar airflow and sensation of nasal patency, (e.g., “Breathe-Right strips” are designed to widen this area for functional purposes. If they become inadvertently separated during surgery, the upper lateral cartilages tend to collapse over time and lead to a pinched middle nasal vault with associated nasal obstruction. If separation does occur, the upper lateral cartilages should be resuspended to the dorsal septum with long-lasting sutures. Support and projection to the middle third of the nose can be lost from any compromise to the integrity of the dorsal septal strut. This can occur from external trauma or iatrogenic injury (e.g., septoplasty or transseptal pituitary surgery) and can lead to collapse of this area and a “saddle nose.” This deformity is not only associated with external stigmata but is also the cause of impaired function with nasal obstruction ( Figure 6-2 ).

Figure 6-2 Saddle-nose deformity. Note the loss of support and projection in the middle third of the nose, specifically caused by the collapse of the nasal septum. This deformity may be due to systemic disease (e.g., Wegener granulomatosis), unrecognized septal hematoma, long-standing septal perforation, or overresection of the cartilaginous septum.
The lower one third of the nose—the nasal tip—has the lower lateral (alar) cartilages as its primary support ( Figure 6-3 ). These cartilages are intimately attached to the caudal border of the upper lateral cartilages in a scroll-like fashion, and to the septum and overlying skin. Disruption of these support mechanisms will affect tip projection and rotation along with nasal function. The external nasal valve is defined by the alar lobule (i.e., the caudal edge of the lateral crus of the lower lateral cartilage), the soft tissue ala, the membranous nasal septum, and the nasal sill inferiorly. A postoperative complication from intranasal incisions is cicatricial scarring within the external nasal valve and consequent obstruction.

Figure 6-3 External skeleton of the nose, anterior oblique and basal views. Note the lower lateral cartilages that provide major support to the nasal tip.
(Drawing reproduced with permission of Marks S: Nasal and sinus surgery. WB Saunders, Philadelphia, 2000, p 9.)

The Septum
The nasal septum is the key midline support structure of the nose and is composed of the quadrilateral cartilage, perpendicular plate of the ethmoid bone, and vomer bone ( Figure 6-4 ). The anterior septal cartilage develops as the unossified portion of the perpendicular plate of the ethmoid. 20 This cartilage attaches posteriorly to the perpendicular plate, posteroinferiorly to the vomer, and superiorly to the nasal bones and upper lateral cartilages. Anteroinferiorly, the cartilage resides within a canal along the anterior nasal spine and maxillary crest. The perpendicular plate of the ethmoid bone represents the posterosuperior portion of the septum. It has two important articulations within the nose. At its posterior edge, the perpendicular plate attaches to the crest of the sphenoid and is a useful landmark for staying in the midline of the nose; despite septal deviations and variations to the intersinus septae, the posterior septum and sphenoid keel make a consistent reference. Secondly, the superior attachment of the perpendicular plate is to the thin, perforated, horizontal cribriform plate at the roof of the nasal cavity. The cribriform plate supports the olfactory bulb and transmits olfactory nerves through multiple foramina. Attached to the cribriform plate is the dura of the anterior cranial fossa. This posterior and superior portion of the septum is rarely dissected but if exposure is needed in this area, tremendous care must be observed when removing this ethmoid portion of the septum in order not to fracture the cribriform or to tear the attached dura. Overly aggressive resection of this portion of the septum may lead to anosmia or to a postoperative cerebrospinal fluid leak.

Figure 6-4 Anatomy of the nasal septum. 1. Quadrangular cartilage; 2. Anterior nasal spine; 3. Posterior septal angle; 4. Middle septal angle; 5. Anterior septal angle; 6. Vomer; 7. Perpendicular plate of the ethmoid bone; 8. Maxillary crest, maxillary component; 9. Maxillary crest, palatine component.
(Drawing courtesy Dr. Daniel G. Becker)
The bulk of the inferior septum is composed of the vomer bone. The vomer articulates directly with the sphenoid bone posteriorly and is another excellent reference for the midline of the nose because deviations to this area are exceedingly rare. It also guides the dissection to the inferior border of the sphenoid sinus. Maintaining a low and midline perspective is essential as one proceeds posteriorly, where important neurovascular structures are found laterally and superiorly. The superior border of the vomer articulates with the perpendicular plate and quadrilateral cartilage through a deep groove in the vomer. Inferiorly, the vomer sits in the trough of the crest of the maxilla and palatine bones. The vomer also represents the medial wall of the choana—the entrance to the nasopharynx.
The bony and cartilaginous components of the nasal septum are covered by a thin mucoperiosteum and mucoperichondrium, which lie beneath a submucosa, lamina propria, and a thick, pseudostratified respiratory epithelium. Because of the embryological continuity between the cartilaginous septum and the perpendicular plate of the ethmoid, this osseocartilaginous junction is a single continuous plane and the mucoperichondrial transition is uninterrupted. This anatomical area allows for an easier subperichondrial dissection as one proceeds posteriorly towards the sphenoid sinus. In contrast, the septal cartilage and vomer bone are embryologically distinct, creating a discontinuous subperichondrial and subperiosteal plane. There are often fibrous tissues interdigitating between these two septal parts, making the subperichondrial transition more tedious and treacherous for perforations. Clinically, this embryological anatomy explains why it is easier to dissect posteriorly while over the perpendicular plate rather than the vomer inferiorly. Once the flap is elevated superiorly, it can be readily continued in an inferior direction with less risk of perforating the flaps. Septal flap perforations are the leading cause of full thickness septal perforations and should be avoided if at all possible.

The Nasal Floor
The nasal floor is composed of the maxilla and the horizontal plates of the palatine bones. The floor slants posteriorly-inferiorly and is characteristically very smooth, allowing for easy elevation of the mucoperiosteal flap. The bone at the nasal sill is typically a sharp crest and dissection here can be challenging. Interestingly, the African-American population tends to have a more rounded and blunted bony sill that facilitates flap elevation here. In the midline, the anterior and posterior nasal spines are at either end of the nasal floor, between which is the right and left maxillary crest. Inferior bony spurs can be large and obstructing, usually arising from either the maxillary crest or the vomer bone. Elevating the septal flap off such a spur can be tedious and often leads to small perforations but their complete removal is often needed.

The Lateral Nasal Wall
The lateral nasal wall is usually not a consideration during transnasal approaches to the sphenoid but it represents a critical area in terms of nasal and sinus function. The bulk of the lateral nasal wall is composed of three (and sometimes four) turbinate bones (see Figure 6-1 ). These turbinate bones modulate and condition nasal airflow. While the superior and middle turbinates are part of the bony ethmoid complex, the inferior turbinate bone exists as an independent structure. As the inferior turbinate forms the lateral border of the internal nasal valve, its hypertrophy is a common source of nasal airway obstruction. Turbinate hypertrophy may be mucosal or bony. Mucosal hypertrophy results from engorgement of the highly vascular lamina propria. Bony hypertrophy is thought to be compensatory for a septal deviation to the contralateral side. Regardless of its cause, inferior turbinate hypertrophy may complicate access to the nasal cavity in the transnasal approach to the sphenoid, and on rare occasion may need to be trimmed. Conservative intervention is the rule here and, more often, simple out-fracturing of the inferior turbinate bone will suffice. If some part of the inferior turbinate is to be resected, one should limit it to the head of the turbinate, i.e. the anterior two centimeters, and preserve the body of the turbinate more posteriorly. Ironically, if excess resection is performed, the normal laminar flow of air will be disrupted and may cause a disturbing sensation of nasal obstruction to many patients.
The middle turbinate sits just superior to the inferior one and is an important landmark for the anatomy of the paranasal sinuses. The maxillary, ethmoid, and frontal sinuses all drain in the space immediately lateral to it. One should avoid lateralizing this bone as it can create outflow obstruction and subsequent sinus problems. The large nasal speculums used for transnasal surgery will occasionally push the middle turbinate laterally. One should inspect the position of this turbinate at the conclusion of the case and medialize it if necessary. On occasion, the turbinate can be filled with an air cell, referred to as a concha bullosa , and impinge into the airway and interfere with access to the sphenoid sinus. Under these circumstances, it can be crushed or partially resected. When performing any dissection or excision of the middle turbinate, care must be taken not to twist the turbinate bone, as this could fracture its superior attachment to the cribriform plate and lead to a cerebrospinal fluid leak.
The superior turbinate, as noted above, is an important landmark for the sphenoid sinus ostium. Although there are several intranasal landmarks for identification of the sphenoid ostia, looking just behind the posteroinferior end of the superior turbinate is perhaps the most reliable. This natural ostium is half way up the front face of the sphenoid so one should avoid drifting further superior than it; it is safer to error low and medial. On occasion, a supreme (or fourth) turbinate is present further superior.

Physiology of Nasal Airflow
The nose has the important physiological function of filtration, warming, and humidification and accomplishes this through its abundant surface area and mucosal physiology. The significance of these roles becomes evident when they are lost; chronic mouth breathing is a troublesome problem that is realized only when nasal obstruction develops. The turbinates dramatically increase mucosal surface area for the moisturization of inspired air to the extent that there is 100% humidification by the time the air reaches the posterior nasal cavity. Alterations in engorgement of nasal mucosa are regulated by the sympathetic and parasympathetic systems, as well as by release of histamines and other vasoactive substances. Because of this vital role that the nasal mucosa plays in nasal airflow, attention should be paid to mucosal preservation when performing nasal (or transnasal) surgery.

Preoperative Considerations
Alterations and abnormalities in nasal anatomy created during transnasal surgery can lead to functional and cosmetic deformities. Moreover, preexisting aberrancies of the nose can influence the approach and are best recognized during the preoperative analysis. Patients with nasal complaints such as obstruction, congestion, recurrent infection, or postnasal drip should be evaluated with nasal endoscopy as part of their standard workup. While anterior nasal abnormalities may be visualized with a standard nasal speculum in the office, posterior nasal deformities as well as diseases within the middle meatus are easily missed without the use of rigid nasal endoscopy. When in question, a sinus CT scan is the gold standard for assessing the sinuses in terms of infection, allergy, etc. While a suppurative infection of the paranasal sinuses is ongoing, it is prudent to avoid further intranasal injury and especially nasal packing. Deviated septums are very common and occur in different forms. The anterior and caudal septum can be deflected, or even dislocated off the anterior nasal spine, thus obstructing visualization and hindering access ( Figure 6-5 ). Intrinsic twisting and deflections can occur within the body of the cartilaginous septum and it is generally easier to dissect on the concave side, allowing for flap elevation with less mobilization of the septum itself. Posterior deflections and spurs can be quickly identified preoperatively with the endoscopes. A history of nasal surgery, particularly a septoplasty, should always be solicited because many times this surgery will remove a large portion of the quadrilateral cartilage, the submucous resection, and the apposing mucosal flaps will be scarred to each other, making flap elevation and septal dissection extremely challenging.

Figure 6-5 Deviated septum, base view. This deviated septum is obstructing access to the left nasal cavity.
Septal perforations should be recognized preoperatively because they will distort the planes of dissection and attempts to work through them will often macerate the edges and enlarge the defect. Individuals at risk for septal perforations include those with a history of prior septal surgery, history of a septal hematoma, nasal trauma, long term nasal intubation, cocaine use, Wegener’s granulomatosis, or sarcoidosis. Clinically, patients may complain of a whistling sound with inhalation, nasal crusting, and epistaxis. Many times it is prudent to leave the septal mucosa undisturbed and swing the entire septum as a composite flap to one side after making a through- and-through incision along the nasal floor.
In addition to intranasal aberrancies, there are external features that should be a part of the complete preoperative assessment. The saddle nose deformity , often described as a “pug nose” or “boxer’s nose,” describes a loss of profile along the middle nasal vault, corresponding to a loss of support from the dorsal septum. The nasal bones and tip are often normally projected. This is often an indication of prior septal surgery and one can anticipate a deficiency in the body of the septum during transnasal work. It can also be a sequela to a large septal perforation where loss of dorsal and caudal support coexist, leading to the classic combination of a saddle nose deformity along with columellar retraction. In order to avoid this deformity, it is imperative to preserve adequate support along the dorsal strut of the cartilaginous septum; specifically, at least 1.5 cm of cartilage should always be left intact. The twisted nose ( Figure 6-6 ) is another external feature that should be detected prior to surgery. It can be a complex deformity with a host of possible etiologies, including the nasal bones, septum, and tip cartilages. Although some patients are born with crooked noses, most commonly the twisted-nose deformity is secondary to trauma and the associated anatomical aberrancies can be anticipated. This deformity can be severe enough that it impairs access to the posterior nasal cavity. On these rare occasions, it may be necessary to realign the nasal pyramid to improve exposure.

Figure 6-6 Twisted-nose deformity. This deformity can involve the nasal bones, dorsal cartilaginous septum, and occasionally, the tip cartilages. Transnasal access to the sphenoid can be limited.

Approaches to the Sphenoid
Although approaches to the sphenoid are covered extensively in subsequent chapters on surgical technique, it is worthwhile to discuss some basic tenets in the context of rhinological evaluation. Transnasal approaches to the sphenoid involve development of tunnels in the submucoperichondrial and submucoperiosteal planes of the septum and nasal floor, respectively. Classically, five tunnels are created with a small periosteal elevator—a unilateral anterior tunnel over the septal cartilage, bilateral inferior floor tunnels to expose the nasal floor, maxillary crest, and vomer, and bilateral posterior septal tunnels for access to the bony septum and the sphenoid. For most right-handed surgeons, elevation of the patient’s left septal flap tends to be easier. Access to these tunnels can be achieved through either the nasal vestibule (the transnasal approach) or from under the upper lip (the sublabial approach). The latter gives the widest exposure and can accommodate the larger self-retaining retractors. Individuals with larger nasal vestibules are suitable for the transnasal approach which obviates the need for an intraoral incision. The bony-cartilaginous junction is disarticulated, taking great care to maintain the important junction at the nasal dorsum. As discussed earlier, disruption at this area will lead to collapse of the dorsal cartilaginous support and the saddle nose deformity. The quadrilateral cartilage is then swung over to the opposite side, using the previously elevated, contralateral floor tunnel. The posterior bony septum is removed with a rongeur or other bone-cutting forceps until the front face of the sphenoid is reached. Superior resection is not necessary and may lead to a cerebrospinal fluid leak. Staying medial and low is continually emphasized. Careful dissection of the nasal mucosa off the sphenoid is then performed and the natural ostium identified. The thin bone at the face of the sphenoid can then be perforated and enlarged with a Kerrison forceps, again in the medial and inferior direction. At the conclusion of the procedure, the septal flaps must be reapproximated to each other in order to avoid a septal hematoma and its future ramifications. This can be accomplished with either nasal packing or a quilting type of stitch that crosses from one side to the other, thus compressing the flaps together. In this manner, the transnasal approach to the sphenoid is performed with attention to achieving optimal exposure through careful dissection and tunneling in the proper avascular planes.

Complications from the transnasal approach to the sphenoid range from immediate postoperative bleeding to long-term, cosmetic and functional issues. Excessive postoperative bleeding after transnasal surgery is usually the result of flap elevation in the incorrect plane or from dissecting too far laterally and injuring one of the branches of the sphenopalatine artery. In most situations, epinephrine-soaked nasal pledgets are sufficient to control nasal bleeding. Arterial bleeding may require direct cauterization and this is best accomplished with a combined suction bovie.
Cerebrospinal fluid leak may occur not only at the surgical site within the sphenoid, but also along the ethmoid roof and its cribriform plate. Care must be taken when manipulating the middle turbinate because of its fragile superior attachment to the ground lamella. When a leak is identified intraoperatively, it is best repaired at that time with intranasal flaps and turbinate grafts; they only rarely heal spontaneously. 21, 22
Postoperative synechia is a common occurrence following extensive intranasal surgery. They arise from a corresponding mucosal disruption on both the septum and the lateral nasal wall. The raw surfaces often heal with a scar band traversing the nasal cavity and may cause septal deflections and nasal obstruction. Less frequently, they may form between the middle turbinate and the lateral nasal wall, blocking sinus drainage into the middle meatus and lead to dependent chronic sinusitis. These are usually managed with scar-band removal under local anesthesia in clinic. Recurrence is not uncommon but can be reduced with aggressive nasal irrigation or even septal splints.
A common complication is a septal perforation ( Figure 6-7 ). These generally arise from corresponding tears in septal flaps during nasal dissection, particularly in areas where the bone or cartilage has been resected. Small disruptions of septal flaps are very common and do not uniformly lead to septal perforations. They usually heal well if carefully draped back and closed with transseptal sutures. Unrecognized septal hematomas are another risk for perforations. Symptoms can vary from nasal crusting, bleeding, the sensation of obstruction, and/or whistling during normal nasal inspiration. Medical management begins with aggressive nasal hygiene, particularly moisturization through lubricants and nasal sprays. Septal buttons can be inserted to “patch” the hole but are often poorly tolerated by patients. Surgical correction is very challenging and involves the mobilization of septal and labial flaps.

Figure 6-7 Septal perforation. Intranasal endoscopic view of a septal perforation seen from the left nasal cavity. Se, septum; MT, middle turbinate; LNW, lateral nasal wall; arrows outline the septal perforation.
(Photo courtesy Joseph K. Han)
Iatrogenic deviated septa can occur if the cartilage is not carefully repositioned back to the midline following dislocation and swinging. Symmetric nasal packing often serves to reduce the septum back to the center. The saddle nose (see Figure 6-2 ) deformity is a common finding, even long term postoperatively, and can arise from several errors in technique. A septal hematoma can lead to resorption of the septal cartilage and loss of support. Disruption of the dorsal bony-cartilaginous junction can allow the dorsal strut to drop. Overly aggressive resection of the cartilaginous septum with failure to preserve at least 1.5 cm of strut can also lead to saddling. The repair of this cosmetic deformity is accomplished with dorsal onlay grafting and can be easily performed. When functional problems also exist, on the other hand, it involves more extensive grafting, including the possibility of harvesting costal cartilage.
The rhinological portion of pituitary surgery is secondary to the neurosurgical focus but complications from the approach can be a significant concern to the patient. A thorough rhinological evaluation before transseptal pituitary surgery is an integral part of this surgery. Subtle findings can influence the decision making in terms of surgical approach or postoperative care.


1 Horsley V. On the technique of operations of the central nervous system. BMJ . 1906;2:411-423.
2 Schloffer H. Erfolgreiche operation eines hypophysentumors auf nasalem wege. Wien. Klin. Wochenschr. . 1907;20:621-624.
3 Cushing H. The pituitary body and its disorders. Clinical states produced by disorders of the hypophysis cerebri. Philadelphia: JB Lippincott, 1912;292-315.
4 Guiot G., Rougerie J., Brion S., et al. L’utilisation des amplificateurs de brilliance en neuro-radiologie et dans la chirgurgie sterotaxique. Ann. Chir. . 1958;12:689.
5 Hardy J., Wisger S.M. Transsphenoidal surgery of pituitary fossa tumors with televised radiofluoroscopic control. J. Neurosurg. . 1965;23:612-620.
6 Thomas R.F., Monacci W.T., Mair E.A. Endoscopic image-guided transethmoid pituitary surgery. Otolaryngol. Head Neck Surg. . 2002;127(5):409-416.
7 Lasio G., Ferroli P., Felisati G., et al. Image-guided endoscopic transnasal removal of recurrent pituitary adenomas. Neurosurgery . 2002;51(1):132-136.
8 Ouaknin G., Hardy J. Microsurgical anatomy of the pituitary gland and the sellar region. Am. Surg. . 1987;53(5):291-297.

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