Challenging Cases in Endocrinology (Contemporary Endocrinology)

CONTEMPORARY ENDOCRINOLOGY ™

Challenging Cases in Endocrinology Edited by

Mark E. Molitch, MD

HUMANA PRESS

Contributors

i

CHALLENGING CASES IN ENDOCRINOLOGY

CONTEMPORARY ENDOCRINOLOGY P. Michael Conn, SERIES EDITOR Developmental Endocrinology: From Research to Clinical Practice, edited by ERICA A. EUGSTER AND O RA HIRSCH PESCOVITZ, 2002 Challenging Cases in Endocrinology, edited by MARK E. MOLITCH, MD, 2002 Selective Estrogen Receptor Modulators: Research and Clinical Applications, edited by ANDREA MANNI AND MICHAEL F. VERDERAME, 2002 Transgenics in Endocrinology, edited by MARTIN MATZUK, CHESTER W. BROWN, AND T. RAJENDRA KUMAR, 2001 Assisted Fertilization and Nuclear Transfer in Mammals, edited by DON P. WOLF AND MARY ZELINSKI-WOOTEN, 2001 Adrenal Disorders, edited by ANDREW N. MARGIORIS AND GEORGE P. CHROUSOS, 2001 Endocrine Oncology, edited by STEPHEN P. ETHIER, 2000 Endocrinology of the Lung: Development and Surfactant Synthesis, edited by CAROLE R. MENDELSON, 2000 Sports Endocrinology, edited by MICHELLE P. WARREN AND NAAMA W. CONSTANTINI, 2000 Gene Engineering in Endocrinology, edited by MARGARET A. SHUPNIK, 2000 Endocrinology of Aging, edited by JOHN E. MORLEY AND LUCRETIA VAN DEN BERG, 2000 Human Growth Hormone: Research and Clinical Practice, edited by ROY G. SMITH AND MICHAEL O. THORNER, 2000 Hormones and the Heart in Health and Disease, edited by LEONARD SHARE, 1999 Menopause: Endocrinology and Management, edited by DAVID B. SEIFER AND ELIZABETH A. KENNARD, 1999

The IGF System: Molecular Biology, Physiology, and Clinical Applications, edited by RON G. ROSENFELD AND CHARLES T. ROBERTS, JR., 1999 Neurosteroids: A New Regulatory Function in the Nervous System, edited by ETIENNEEMILE BAULIEU, MICHAEL SCHUMACHER, AND PAUL ROBEL, 1999 Autoimmune Endocrinopathies, edited by ROBERT VOLPÉ, 1999 Hormone Resistance Syndromes, edited by J. LARRY JAMESON, 1999 Hormone Replacement Therapy, edited by A. WAYNE MEIKLE, 1999 Insulin Resistance: The Metabolic Syndrome X, edited by GERALD M. REAVEN AND AMI LAWS, 1999 Endocrinology of Breast Cancer, edited by ANDREA MANNI, 1999 Molecular and Cellular Pediatric Endocrinology, edited by STUART HANDWERGER, 1999 Gastrointestinal Endocrinology, edited by GEORGE H. GREELEY, JR., 1999 The Endocrinology of Pregnancy, edited by FULLER W. BAZER, 1998 Clinical Management of Diabetic Neuropathy, edited by ARISTIDIS VEVES, 1998 G Proteins, Receptors, and Disease, edited by ALLEN M. SPIEGEL, 1998 Natriuretic Peptides in Health and Disease, edited by WILLIS K. SAMSON AND ELLIS R. LEVIN, 1997 Endocrinology of Critical Disease, edited by K. PATRICK OBER, 1997 Diseases of the Pituitary: Diagnosis and Treatment, edited by MARGARET E. WIERMAN, 1997 Diseases of the Thyroid, edited by LEWIS E. BRAVERMAN, 1997 Endocrinology of the Vasculature, edited by JAMES R. SOWERS, 1996

Contributors

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CHALLENGING CASES IN ENDOCRINOLOGY Edited by

MARK E. MOLITCH, MD Center for Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, IL

HUMANA PRESS TOTOWA, NEW JERSEY

© 2002 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel: 973-256-1699; Fax: 973-256-8341; E-mail: [email protected]; Website: http://humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication. Cover Illustration: Left: Cohesive groups of benign follicular cells. (See Fig. 1, p. 69.) Center: Coronal section through the pituitary from a T1-weighted MRI image. (See Fig. 1, p. 39.) Right: CT scan of a 7.2. cm adrenal mass. (See Fig. 1, p. 157.) Cover design by Patricia F. Cleary. Production Editor: Mark J. Breaugh. All articles, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. This publication is printed on acid-free paper. ' ANSI Z39.48-1984 (American National Standards Institute) Permanence of Paper for Printed Library Materials. Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $10.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [0-89603-914-5/02 $10.00 + $00.25]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging-in-Publication Data Challenging cases in endocrinology/edited by Mark E. Molitch. p. cm. — (Contemporary endocrinology) Includes bibliographical references and index. ISBN 0-89603-914-5 (alk. paper) 1. Endocrinology--Case studies. I. Molitch, Mark E. II. Contemporary endocrinology (Totowa, NJ) [DNLM: 1. Endocrine Diseases--diagnosis. 2. Endocrine Diseases--therapy. WK 140 D569 2002] RC649.5 .D544 2002 616.4--dc21

Contributors P REFACE

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I enjoy seeing patients, as I think most endocrinologists do. One of the things I believe we enjoy most is seeing patients who provide challenges to us, so that we have to think a little harder to find the diagnosis and to be creative in our disease management. Going to the literature and textbooks—often via the computer—to look up the latest information, discussing cases with colleagues, reaching for help by way of telephone or email from more distant colleagues with greater expertise, are part of what we do on an everyday basis to provide the best care for our patients and also to provide intellectual stimulation for ourselves. This continued desire on our part to meet such challenging cases head-on and to stimulate ourselves intellectually are the reasons I am confident readers will like Challenging Cases in Endocrinology. I have asked experts in their fields to provide for us accounts of those difficult cases that have required of them extra effort and creative thinking in diagnosis and management. You will be able to follow with them how they did what they did, and why. They have also provided detailed, up-to-date, referenced discussions to put their cases into context. In this way, you will be able to bring much of this information into daily use in your own practices, and the references we have provided will allow you to look up additional material as needed. As editor, I have read all of these cases and have personally picked up information and a number of tips that I have already put to use in my own practice. This, therefore, is a book for the practicing endocrinologist, whether a fellow still in training, a full-time clinician out in practice for 25 years, or a clinician/academic who only sees patients one-half day per week. You can take it on the airplane with you or read a case at a time when you can fit it in. Very few of the cases are straightforward and many provide twists or turns—almost as if you were reading a novel. I wish to thank the authors of these chapters for taking the time out of their busy schedules to write up their cases and for sharing their clinical expertise with us. I also wish to thank Ms. Joella Ackerman for helping me keep things organized and helping with the editing. Mr. Paul Dolgert and the editorial and production staff at Humana Press have been very supportive. Finally, I would like to thank my family—Susan, Tamara, Ethan, and Michael—who are used to seeing me at home working at the computer in the evenings and on weekends, for supporting me in this endeavor. Mark E. Molitch, MD

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Contributors C ONTENTS

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Preface ........................................................................................................ v Contributors .............................................................................................. ix 1 2 3 4 5 6 7 8 9 10 11 12

Pituitary Tumors ............................................................................... 1 Moises Mercado and Mark E. Molitch Hypopituitarism .............................................................................. 17 Baha M. Arafah and Mona P. Nasrallah Posterior Pituitary: Disorders of Water Metabolism ..................... 33 Lisa L. Wong and Joseph G. Verbalis Hyperthyroidism ............................................................................. 51 David S. Cooper Hypothyroidism and Thyroiditis .................................................... 67 Donald A. Meier and Michael M. Kaplan Thyroid Cancer ............................................................................... 81 Richard T. Kloos and Ernest L. Mazzaferri Cushing’s Syndrome ..................................................................... 119 James W. Findling Adrenal Insufficiency and Adrenal Cancer .................................. 137 Erik K. Alexander and Robert Dluhy Pheochromocytoma ....................................................................... 155 Mary P. Gillam and Lewis Landsberg Hypercalcemia and Hyperparathyroidism .................................... 185 Bart L. Clarke and Sundeep Khosla Hypoparathyroidism and Hypocalcemia ...................................... 201 Elena I. Barengolts and Subhash C. Kukreja Metabolic Bone Disease ............................................................... 215 Michael Kleerekoper, Hisham Alrefai, Louis Afonso, and Bharat Raman

13

Male Reproductive Endocrinology ............................................... 231 Shalender Bhasin, Atam B. Singh, and Robert Christiansen

14

Disorders of Female Reproduction ............................................... 253 Jared C. Robins and Robert Rebar

15

Endocrine Problems in Pregnancy ................................................ 269 Lisa P. Purdy and Boyd E. Metzger

16

Type 1 Diabetes Mellitus .............................................................. 287 J. Woody Sistrunk and Bruce R. Zimmerman*

* Deceased vii

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Contents

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Type 2 Diabetes Mellitus ............................................................. 303 Neelima V. Chu and Robert R. Henry

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Hypoglycemia .............................................................................. 325 Neena Natt and F. John Service

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Disorders of Lipoprotein Metabolism ......................................... 337 Ira J. Goldberg and Phillip Bukberg

20

Disorders of Puberty .................................................................... 349 Dennis M. Styne

21

Disorders of Growth and Development....................................... 375 Erick J. Richmond and Alan D. Rogol

22

Multiple Endocrine Neoplasia Syndromes .................................. 391 Kelly L. Wirfel, Douglas B. Evans, Jeffery E. Lee, Helmuth Goepfert, and Robert F. Gagel

Index...................................................................................................... 405

Contributors C ONTRIBUTORS

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LOUIS AFONSO, MD, Division of Cardiology, Veterans Administration Medical Center, Wayne State University, Detroit, MI ERIK K. ALEXANDER, MD, Division of Endocrine–Hypertension, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA HISHAM ALREFAI, MD, Division of Endocrinology, Wayne State University, Detroit, MI BAHA M. ARAFAH, MD, Division of Clinical and Molecular Endocrinology, Case Western Reserve University; University Hospitals of Cleveland, Cleveland, OH ELENA I. BARENGOLTS, MD, University of Illinois Medical School, Medical Service, VA Chicago Health Care System–West Side Division, Chicago, IL SHALENDER BHASIN, MD, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA PHILLIP BUKBERG, MD, St. Vincent’s Hospital, New York, NY ROBERT CHRISTIANSEN, MD, Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, CA NEELIMA V. CHU, MD, Division of Endocrinology and Metabolism, University of California–San Diego Medical School, La Jolla, CA BART L. CLARKE, MD, Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN DAVID S. COOPER, MD, Division of Endocrinology, Sinai Hospital of Baltimore; The Johns Hopkins Hospital; Johns Hopkins Medical School, Baltimore, MD ROBERT DLUHY, MD, Division of Endocrine–Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA DOUGLAS B. EVANS, MD, Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX JAMES W. FINDLING, MD, Medical College of Wisconsin, Endocrine Diabetes Center, St. Luke’s Medical Center, Milwaukee, WI ROBERT F. GAGEL, MD, Section of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX MARY P. GILLAM, MD, Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, IL HELMUTH GOEPFERT, MD, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX IRA J. GOLDBERG, MD, Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, NY ROBERT R. HENRY, MD, Division and Endocrinology and Metabolism, University of California–San Diego Medical School, Section of Diabetes, Endocrinology & Metabolism, Veterans Administration San Diego Healthcare System, La Jolla, CA MICHAEL M. KAPLAN, MD, Associated Endocrinologists, West Bloomfield, MI; Departments of Nuclear Medicine and Internal Medicine, William Beaumont Hospital, Royal Oak, MI SUNDEEP KHOSLA, MD, Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN ix

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Contributors

MICHAEL KLEEREKOPER, MD, Division of Endocrinology, Wayne State University, Detroit, MI RICHARD T. KLOOS, MD, Divisions of Endocrinology, Diabetes, and Metabolism & Nuclear Medicine, Departments of Internal Medicine and Radiology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University School of Medicine, Columbus, OH SUBHASH C. KUKREJA, MD, University of Illinois Medical School, Medical Service, VA Chicago Health Care System–West Side Division, Chicago, IL LEWIS LANDSBERG, MD, Northwestern University Medical School, Chicago, IL JEFFREY E. LEE, MD, Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX ERNEST L. MAZZAFERRI, MD, Department of Internal Medicine, Ohio State University School of Medicine, Columbus, OH DONALD A. MEIER, MD, Associated Endocrinologists, West Bloomfield, MI; Departments of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI MOISES MERCADO, MD, Endocrinology Section, Hospital de Especialidades, Centro Medico Nacional, México City, México BOYD E. METZGER, MD, Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, IL MARK E. MOLITCH, MD, Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, IL MONA P. NASRALLAH, MD, Division of Clinical and Molecular Endocrinology, Case Western Reserve University; University Hospitals of Cleveland, Cleveland, OH NEENA NATT, MD, Division of Endocrinology, Diabetes and Metabolism, Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN LISA P. PURDY, MD, CM, Center for Endocrinology, Metabolism, Molecular Medicine, Northwestern University Medical School, Chicago, IL BHARAT RAMAN, MD, Department of Medicine, University of North Dakota, Grand Forks, ND ROBERT REBAR, MD, American Society for Reproductive Medicine, Birmingham, AL ERICK J. RICHMOND, MD, Division of Pediatric Endocrinology, University of Virginia School of Medicine, Charlottesville, VA JARED C. ROBINS, MD, Department of Obstetrics and Gynecology, University of Cincinnati Medical School, Cincinnati, OH ALAN D. ROGOL, MD, PhD, Insmed Incorporated, Glen Allen, VA; Medical College of Virginia, Virginia Commonwealth University, Richmond, VA; Division of Pediatric Endocrinology, University of Virginia School of Medicine, Charlottesville, VA F. JOHN SERVICE, MD, PhD, Mayo Medical School, Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, MN ATAM B. SINGH, MD, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA J. WOODY SISTRUNK, MD, Mississippi Baptist Medical Center, Jackson, MS DENNIS M. STYNE, MD, Section of Pediatric Endocrinology, University of California– Davis Medical School, Davis, CA JOSEPH G. VERBALIS, MD, Division of Endocrinology, Georgetown University Medical Center, Washington, DC

Contributors

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KELLY L. WIRFEL, MD, Department of Endocrinology, The University of Texas Medical School, Houston, TX LISA L. WONG, MD, Division of Endocrinology, Georgetown University Medical Center, Washington, DC BRUCE ZIMMERMAN, MD, Deceased, formerly of Division and Endocrinology and Metabolism, Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN

Chapter 1 / Pituitary Tumors

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Pituitary Tumors Moises Mercado, MD and Mark E. Molitch, MD CONTENTS CASE #1: ADOLESCENT WITH A PROLACTINOMA CASE #2: ACROMEGALY WITH MINIMAL GROWTH HORMONE ELEVATION CASE #3: 31-YR-OLD MAN WITH HYPERTHYROIDISM AND HYPOKALEMIC PERIODIC P ARALYSIS AS A R ESULT OF A THYROTROPINOMA CASE #4: 39-YR-OLD MAN WITH A PITUITARY INCIDENTALOMA

CASE #1: ADOLESCENT WITH A PROLACTINOMA Case Description A 27-yr-old woman initially presented to the emergency room in 1988 at age 16 with increasing headaches and decreased visual acuity and was found to have a visual field defect. She also had primary amenorrhea. A computed tomography (CT) scan showed a 2 × 3-cm suprasellar mass and she was admitted to the neurosurgery service. She was operated on for what was thought then to be a craniopharyngioma. Her examination at that time showed a modestly obese young girl of normal height with Tanner Stage IV breast and pubic hair development. Preoperative laboratory results that were not available at the time of the surgery showed a serum PRL of 1270 ng/mL, a cortisol of 6.6 µg/ dL, a T4 of 4.8 µg/dL, a growth hormone (GH) of 1.4 ng/mL, a luteinizing hormone (LH) of 3.8 mIU/mL, and a follicle-stimulating hormone (FSH) of 17.4 mIU/mL. Postoperatively, her PRL was 415 ng/mL and she was referred to the endocrine service where testing showed panhypopituitarism. A postoperative MRI showed little change in the tumor size. She was begun on l-thyroxine, prednisone, and bromocriptine. Over the course of the next 2 yr, despite many attempts, the bromocriptine dose could not be increased sufficiently to normalize PRL levels without causing severe nausea. The highest dose she was able to tolerate was 10 mg/d with a resultant PRL of 95 ng/mL, but because of nausea she rarely stayed on this dose. She tried intravaginal bromocriptine but refused to take it regularly via this route and her PRL levels increased to over 600 ng/dL.

From: Contemporary Endocrinology: Challenging Cases in Endocrinology Edited by: M. E. Molitch © Humana Press Inc., Totowa, NJ

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Mercado and Molitch Table 1 Stepwise Decrease in Prolactin Levels with Stepwise Increase in Cabergoline Dose/Wk in Case 1

Date

11/13/96 5/5/97 8/4/97 12/15/97 3/30/98

PRL (ng/dL) 655 Dose (mg/wk) 0

288 0.5

329 0.5

311 1.0

7/20/98

10/7/98

127 3.0

109 4.0

172 2.0

11/16/98 4/12/99 7/9/99 96 6.0

65 8.0

38 8.0

Because of her psychological refusal to accept her illness and need for medication, as well as the nausea that occurred on taking bromocriptine, she stopped all her medication frequently for months at a time with failure to return for follow-up visits. She was also tried on pergolide in doses up to 0.25 mg/d but her PRL remained over 100 ng/mL and attempts to increase the dose resulted in nausea and stopping medication. Off medication, her PRL would rise to levels in the 1600 ng/mL range. Her parents divorced shortly after her surgery and were unable to provide adequate emotional support and direction. She was advised to seek psychiatric counseling many times, but did not do so. Despite the poor medication compliance, with intermittently quite high PRL levels, periodic magnetic resonance imaging (MRI) scans showed no change in tumor size. However, in 1995, after not being seen for 8 mo and off dopamine agonists during all that time, her PRL was 7101 ng/mL and an MRI showed a considerable enlargement of the residual tumor with suprasellar extension bowing the optic chiasm and she had a right visual field defect. She underwent transsphenoidal surgery with improvement in her visual fields and her postoperative PRL level was 1123 ng/mL. Postoperatively, she was again noncompliant with bromocriptine and her other medications with a rise in PRL to 1838 ng/mL. In March 1997, she was started on cabergoline and experienced a stepwise reduction in PRL levels with each stepwise increase in her cabergoline dose (see Table 1). Finally, on a dose of 8 mg/wk, her PRL levels reached 38 ng/mL and an MRI showed a marked decrease in the size of her residual tumor. However, despite near normalization of her PRL levels, she remained amenorrheic and a dual X-ray absorptiometry study showed that her bone mineral density at the lumbar spine was 74% of normal young women. In July 1999, she was started for the first time on oral contraceptives for estrogen replacement along with her 8 mg/wk of cabergoline. As of November 1999, she has missed two return visits.

Discussion This case illustrates a number of important features of the management of a patient with a prolactinoma. First, is her initial presentation at age 16 with amenorrhea and a large macroadenoma. Children and adolescents may present with growth arrest, pubertal delay, or primary amenorrhea in addition to the more standard presentations of galactorrhea and/or oligo/amenorrhea (1–4). In contrast to the tumor size distribution of patients in adults, almost two-thirds of children with prolactinomas have large macroadenomas in reported series, even allowing for possible selection bias because of reporting from neurosurgical units. Furthermore, the percentage of patients resistant to dopamine agonists may be higher than in adults, with Colao et al. (4) reporting that PRL levels were normalized in only 10/26 children and adolescents taking bromocriptine, 5/15 taking quinagolide, and 15/20 taking cabergoline. The reasons for the high percentage of large macroade-

Chapter 1 / Pituitary Tumors

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nomas and the relative resistance to dopamine agonists are not known, but it is tempting to speculate that the tumor growth may be linked to resistance to endogenous dopamine. Her initial referral to neurosurgery was unusual and was caused, in part, by her being admitted to the neurosurgery service from the emergency room and then not waiting for the results of hormone testing before going to surgery. Generally, most patients with prolactinomas now do not have surgery; rather, they are treated with dopamine agonists, especially those with large tumors. In a compilation of data from 34 published series, it was shown that 973/1321 (73.7%) microadenomas and 415/1279 (32.4%) macroadenomas were reported as being curatively resected, i.e., having PRL levels normalized by 1–12 wk following surgery (5). From these series, recurrence rates for microadenomas (114/544 = 21.0%) and macroadenomas (50/253 = 19.8%) are similar (5). Thus, the long-term surgical cure rate for microadenomas is 58%, and that for macroadenomas is 26%, understanding that these numbers are derived from patients in whom the neurosurgeon thought there was a possibility of cure. For patients with giant prolactinomas and those with considerable cavernous sinus invasion, the chance for surgical cure is essentially zero. Complications from transsphenoidal surgery for microadenomas are quite infrequent, the mortality rate being 0.5–0.9%, and the major morbidity rate being about 1.5–6% (6,7). Transient diabetes insipidus (DI) is quite common with transsphenoidal surgery for both micro- and macroadenomas, but permanent DI occurs in only about 1% of surgeries on macroadenomas (6,7). Hypopituitarism is common in patients with macroadenomas prior to surgery as a result of mass effects, occurring in more than 50% of patients (6,7). With surgery, both further worsening or improvement may occur (6,7). Surgery involving craniotomy is much more hazardous. It is clear that the less experienced the surgeon, the greater the rate of complications (7). In contrast, bromocriptine generally restores normal PRL levels in about 80–85% of patients with prolactinomas of all sizes, usually with a reduction in tumor size. In a compilation of several series with a total of 302 patients with macroadenomas, 76.8% had some tumor size decrease in response to bromocriptine with periods of observation ranging from 6 wk to more than 10 yr (5). Ten series quantitated their tumor size reductions in a total of 112 patients; 45 (40.2%) had a >50% reduction in tumor size, 32 (28.6%) had a 25–50% reduction in tumor size, 14 (12.5%) had a 50% tumor size reduction, 47% experiencing a 25–50% reduction, 7% having a < 25% reduction, and 21% having no change in tumor size. In a recent series of 27 patients who had all been previously shown to be resistant to bromocriptine or quinagolide (CV205502), Colao et al. (20) showed that cabergoline was able to normalize PRL levels in 15 of 19 patients with macroadenomas and all 8 patients with microadenomas; tumor shrinkage was documented in 9 of the 19 macroadenomas and 4 of the 8 microadenomas (20). Thus, our patient was finally able to tolerate cabergoline in a dose sufficient to normalize PRL levels. Most patients have a rapid fall in PRL with just modest doses of dopamine agonist. However, a small percentage, perhaps