Larsen: Williams Textbook of Endocrinology, 10th ed., Copyright © 2003 Elsevier


Section 1 - Hormones and Hormone Action
1 - Principles of Endocrinology
2 - The Endocrine Patient
3 - Genetic Control of Peptide Hormone Formation
4 - Mechanism of Action of Hormones That Act on Nuclear Receptors
5 - Mechanism of Action of Hormones That Act at the Cell Surface
6 - Laboratory Techniques for Recognition of Endocrine Disorders
Section 2 - Hypothalamus and Pituitary
7 - Neuroendocrinology
8 - Anterior Pituitary
9 - Posterior Pituitary Gland
Section 3 - Thyroid
10 - Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid
Disorders
11 - Thyrotoxicosis
12 - Hypothyroidism and Thyroiditis
13 - Nontoxic Goiter and Thyroid Neoplasia
Section 4 - Adrenal Cortex and Endocrine Hypertension
14 - The Adrenal Cortex
15 - Endocrine Hypertension
Section 5 - Reproduction
16 - The Physiology and Pathology of the Female Reproductive Axis
17 - Fertility Control: Current Approaches and Global Aspects
18 - Disorders of the Testes and the Male Reproductive Tract
19 - Sexual Dysfunction in Men and Women
Section 6 - Endocrinology and the Life Span
20 - Endocrine Changes in Pregnancy
21 - Endocrinology of Fetal Development

22 - Disorders of Sex Differentiation
23 - Normal and Aberrant Growth
24 - Puberty: Ontogeny, Neuroendocrinology, Physiology, and Disorders
25 - Endocrinology and Aging
Section 7 - Mineral Metabolism
26 - Hormones and Disorders of Mineral Metabolism
27 - Metabolic Bone Disease


27 - Metabolic Bone Disease
28 - Kidney Stones
Section 8 - Disorders of Carbohydrate and Lipid Metabolism
29 - Type 2 Diabetes Mellitus
30 - Type 1 Diabetes Mellitus
31 - Complications of Diabetes Mellitus
32 - Glucose Homeostasis and Hypoglycemia
33 - Obesity
34 - Disorders of Lipid Metabolism
Section 9 - Polyendocrine Disorders
35 - Pathogenesis of Endocrine Tumors
36 - Multiple Endocrine Neoplasia
37 - The Immunoendocrinopathy Syndromes
Section 10 - Paraendocrine and Neoplastic Syndromes
38 - Gastrointestinal Hormones and Gut Endocrine Tumors
39 - Endocrine-Responsive Cancer
40 - Humoral Manifestations of Malignancy
41 - Carcinoid Tumors, Carcinoid Syndrome, and Related Disorders
Appendix: Reference Values



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Larsen: Williams Textbook of Endocrinology, 10th ed., Copyright © 2003 Elsevier

I

Williams Textbook of Endocrinology

TENTH EDITION
P. Reed Larsen MD, FACP, FRCP
Professor of Medicine
Harvard Medical School
Chief, Division of Endocrinology, Diabetes and Hypertension
Brigham and Women's Hospital
Boston, Massachusetts

Henry M. Kronenberg MD
Professor of Medicine
Harvard Medical School
Chief, Endocrine Unit
Massachusetts General Hospital
Boston, Massachusetts

Shlomo Melmed MD
Senior Vice President, Academic Affairs
Cedars Sinai Research Institute
Professor of Medicine and Associate Dean



University of California, Los Angeles, School of Medicine
Los Angeles, California

Kenneth S. Polonsky MD
Adolphus Busch Professor and Chairman
Department of Medicine
Professor, Department of Cell Biology and Physiology
Washington University School of Medicine
St. Louis, Missouri

SAUNDERS
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Larsen: Williams Textbook of Endocrinology, 10th ed., Copyright © 2003 Elsevier

II

SAUNDERS
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WILLIAMS TEXTBOOK OF ENDOCRINOLOGY
ISBN 0-7216-9184-6
Copyright © 2003, 1998, 1992, 1985, 1981, 1974, 1968, 1962, 1955 by Elsevier
Science (USA).
Copyright 1950 by W.B. Saunders Company
Copyright renewed 1990 by A.B. Williams, R.I. Williams
Copyright renewed 1983 by William H. Daughaday
Copyright renewed 1978 by Robert H. Williams
All rights reserved. No part of this publication may be reproduced or transmitted in any
form or by any means, electronic or mechanical, including photocopy, recording, or any
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Library of Congress Cataloging-in-Publication Data
Williams textbook of endocrinology/P. Reed Larsen ... [et al.].10th ed.

p.; cm.
ISBN 0-7216-9184-6
1. Endocrinology. 2. Endocrine glandsDiseases. I. Williams, Robert Hardin. II.
Larsen, P. Reed.
RC648 .T48 2002
616.4dc21
DNLM/DLC
2002019193
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but not limited to others in the same company or organization, without the express prior written permission of MD Consult, except as otherwise expressly permitted under fair
use provisions of U.S. Copyright Law. Subscriber Agreement

Larsen: Williams Textbook of Endocrinology, 10th ed., Copyright © 2003 Elsevier

III

Contributors


Eli Y. Adashi

Presidential Professor of Obstetrics and Gynecology
and John A. Dixon Professor and Chair,
Department of Obstetrics and Gynecology,
University of Utah Health Sciences Center,
Salt Lake City, Utah
The Physiology and Pathology of the Female Reproductive Axis;
Fertility Control: Current Approaches and Global Aspects
Lloyd P. Aiello


Associate Professor of Ophthalmology,
Harvard Medical School;
Assistant Director,
Beetham Eye Institute;
Investigator and Head,
Section of Eye Research,
Joslin Diabetes Center,
Boston, Massachusetts
Complications of Diabetes Mellitus
Andrew Arnold

Murray-Heilig Chair in Molecular Medicine
and Professor of Medicine and Genetics,
University of Connecticut School of Medicine;
Director, Center for Molecular Medicine,
and Chief, Division of Endocrinology and Metabolism,
University of Connecticut,

Farmington, Connecticut
Pathogenesis of Endocrine Tumors
Jennifer Berman

Assistant Professor,
Department of Urology,
David Geffen School of Medicine at University of California, Los Angeles;
Attending Surgeon,
UCLA Medical Center;
Co-Director, Female Sexual Medicine Center at UCLA,
Los Angeles, California
Sexual Dysfunction in Men and Women

IV

Laura Berman


Assistant Professor,
Department of Urology,
David Geffen School of Medicine at University of California, Los Angeles;
Co-Director, Female Sexual Medicine Center at UCLA,
Los Angeles, California
Sexual Dysfunction in Men and Women
Shalender Bhasin

Professor of Medicine,
University of California, Los Angeles,
School of Medicine;
Chief, Division of Endocrinology, Metabolism, and Molecular Medicine,

Charles Drew University and King-Drew Medical Center,
Los Angeles, California
Sexual Dysfunction in Men and Women
Andrew J. M. Boulton

Professor of Medicine,
University of Manchester;
Consultant Physician,
Manchester Royal Infirmary,
Manchester, United Kingdom
Complications of Diabetes Mellitus
Robin P. Boushey

General Surgery Resident,
Department of Surgery,
University of Toronto,
Toronto, Ontario, Canada


Gastrointestinal Hormones and Gut Endocrine Tumors
Glenn D. Braunstein

Professor of Medicine,
University of California, Los Angeles,
School of Medicine;
Chairman, Department of Medicine,
The James R. Klinenberg, MD, Chair in Medicine,
Cedars-Sinai Medical Center,
Los Angeles, California
Endocrine Changes in Pregnancy

F. Richard Bringhurst

Associate Professor of Medicine,
Harvard Medical School;
Physician,
Massachusetts General Hospital,
Boston, Massachusetts
Hormones and Disorders of Mineral Metabolism

V

Michael Brownlee

Anita and Jack Saltz Professor of Diabetes Research
and Professor of Medicine and Pathology,
Albert Einstein College of Medicine,
Bronx, New York
Complications of Diabetes Mellitus
Serdar E. Bulun


Associate Professor of Obstetrics-Gynecology and Molecular Genetics;
Director, Division of Reproductive Endocrinology and Infertility,
University of Illinois,
Chicago, Illinois
The Physiology and Pathology of the Female Reproductive Axis
Charles F. Burant

Associate Professor,
Department of Internal Medicine,

University of Michigan;
Attending Physician,
University of Michigan Hospitals,
Ann Arbor, Michigan
Type 2 Diabetes Mellitus
John B. Buse

Associate Professor of Medicine;
Chief, Division of General Medicine and Clinical Epidemiology;
Director, Diabetes Care Center,
University of North Carolina School of Medicine,
Chapel Hill, North Carolina
Type 2 Diabetes Mellitus;
Type 1 Diabetes Mellitus
David A. Bushinsky

Professor of Medicine and of Pharmacology and Physiology,
University of Rochester School of Medicine and Dentistry;
Chief, Nephrology Unit,


Strong Memorial Hospital,
Rochester, New York
Kidney Stones
Judy L. Cameron

Associate Professor,
Department of Psychiatry,
University of Pittsburgh,
Pittsburgh, Pennsylvania;

Associate Scientist,
Oregon National Primate Research Center,
Oregon Health and Science University,
Portland, Oregon
Neuroendocrinology

VI

Christin Carter-Su

Professor of Physiology;
Associate Director,
Michigan Diabetes Research and Training Center,
University of Michigan Medical School,
Ann Arbor, Michigan
Mechanism of Action of Hormones That Act at the Cell Surface
Roger D. Cone

Senior Scientist,
Vollum Institute;
Associate Professor,
Department of Cell and Developmental Biology,
Oregon Health and Science University,


Portland, Oregon
Neuroendocrinology
Felix A. Conte

Professor of Pediatrics,

Department of Pediatrics,
University of California, San Francisco,
School of Medicine,
San Francisco, California
Disorders of Sex Differentiation
Philip E. Cryer

Irene E. and Michael M. Karl Professor of Endocrinology and Metabolism in Medicine,
Washington University School of Medicine;
Chief of Endocrinology, Diabetes, and Metabolism,
Barnes-Jewish Hospital,
St. Louis, Missouri
Glucose Homeostasis and Hypoglycemia
Terry F. Davies

Professor of Medicine and Director,
Division of Endocrinology,
Diabetes and Bone Diseases,
Mount Sinai School of Medicine;
Attending Physician,
Mount Sinai Hospital,
New York, New York
Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid Disorders;
Thyrotoxicosis;
Hypothyroidism and Thyroiditis
Marie B. Demay


Associate Professor of Medicine,
Harvard Medical School;

Associate Physician,
Massachusetts General Hospital,
Boston, Massachusetts
Hormones and Disorders of Mineral Metabolism

VII

Robert G. Dluhy

Professor of Medicine,
Harvard Medical School;
Clinical Chief,
Division of Endocrinology, Diabetes and Hypertension,
Brigham and Women's Hospital,
Boston, Massachusetts
Endocrine Hypertension
Daniel J. Drucker

Professor of Medicine,
University of Toronto Faculty of Medicine;
Director, Banting and Best Diabetes Centre,
Toronto General Hospital,
Toronto, Ontario, Canada
Gastrointestinal Hormones and Gut Endocrine Tumors
George S. Eisenbarth


Professor of Pediatrics, Medicine, and Immunology,
University of Colorado School of Medicine;
Executive Director,

Barbara Davis Center for Childhood Diabetes,
Denver, Colorado
Type 1 Diabetes Mellitus;
The Immunoendocinropathy Syndromes
Joel K. Elmquist

Associate Professor of Medicine and Neurology,
Harvard Medical School,
Division of Endocrinology,
Beth Israel Deaconess Medical Center,
Boston, Massachusetts
Neuroendocrinology
Robert V. Farese Jr.

Professor of Medicine,
University of California, San Francisco;
Senior Investigator,
Gladstone Institute of Cardiovascular Disease,
San Francisco, California
Disorders of Lipid Metabolism
Daniel D. Federman

Carl W. Walter Distinguished Professor of Medicine and Medical Education,
Harvard Medical School;
Senior Physician,
Brigham and Women's Hospital and Massachusetts General Hospital,
Boston, Massachusetts
The Endocrine Patient



VIII

Sebastiano Filetti

Professor of Medicine,
Department of Internal Medicine,
University of Sapienza,
and Chairman of Internal Medicine, and Policlinico Umberto I,
Rome, Italy
Nontoxic Goiter and Thyroid Neoplasia
Delbert A. Fisher

Professor of Pediatrics and Medicine Emeritus,
University of California, Los Angeles,
School of Medicine;
Vice President, Science and Innovation,
Quest Diagnostics Inc.,
Nichols Institute,
San Juan Capistrano, California
Endocrinology of Fetal Development
Eli Friedman

Distinguished Teaching Professor of Medicine,
State University of New York;
Chief, Division of Renal Disease,
Department of Medicine,
Downstate Medical Center;
Attending Physician,
University Hospital of Brooklyn and Kings County Hospital,
Brooklyn, New York

Complications of Diabetes Mellitus


Robert F. Gagel

Professor of Medicine,
Division of Internal Medicine,
University of Texas/M.D. Anderson Cancer Center;
Adjunct Professor of Medicine, Internal Medicine, and Cell Biology,
Baylor College of Medicine,
Houston, Texas
Multiple Endocrine Neoplasia
Peter A. Gottlieb

Assistant Professor of Pediatrics and Medicine,
Barbara Davis Center for Childhood Diabetes,
University of Colorado Health Sciences Center,
Denver, Colorado
The Immunoendocrinopathy Syndromes
James E. Griffin

Professor of Internal Medicine
and Diana and Richard C. Strauss Professor in Biomedical Research,
The University of Texas Southwestern Medical Center,
Dallas, Texas
Disorders of the Testes and Male Reproductive Tract

IX

Melvin M. Grumbach



Edward B. Shaw Emeritus Professor of Pediatrics
and Emeritus Chairman, Department of Pediatrics,
University of California, San Francisco,
San Francisco, California
Disorders of Sex Differentiation;
Puberty: Ontogeny, Neuroendocrinology, Physiology, and Disorders
Joel F. Habener

Professor of Medicine,
Harvard Medical School;
Associate Physician and Chief,
Laboratory of Molecular Endocrinology,
Massachusetts General Hospital;
Investigator,
Howard Hughes Medical Institute,
Boston, Massachusetts
Genetic Control of Peptide Hormone Formation
Ian D. Hay

Professor of Medicine,
Mayo Medical School;
Consultant in Endocrinology and Internal Medicine,
Mayo Clinic,
Rochester, Minnesota
Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid Disorders;
Nontoxic Goiter and Thyroid Neoplasia
Wayne J. G. Hellstrom


Professor of Urology
and Chief, Section of Andrology and Male Dysfunction,
Tulane University Health Sciences Center,
New Orleans, Louisiana


Sexual Dysfunction in Men and Women
Ieuan A. Hughes

Professor of Paediatrics
and Head, Department of Paediatrics,
University of Cambridge;
Honorary Consultant,
Paediatric Endocrinology,
Addenbrooke Hospital,
Cambridge, United Kingdom
Disorders of Sex Differentiation
Michael Kafrissen

Adjunct Professor,
Maternal and Child Health,
University of North Carolina School of Medicine, Chapel Hill, North Carolina;
Vice President,
Ortho-McNeil Pharmaceutical Co.,
Raritan, New Jersey
Fertility Control: Current Approaches and Global Aspects

X

George G. Klee


Professor of Laboratory Medicine,
Department of Laboratory Medicine,
Mayo Medical School;
Consultant in Clinical Pathology,
Department of Laboratory Medicine and Pathology,
Mayo Clinical Hospitals,
Rochester, Minnesota


Laboratory Techniques for Recognition of Endocrine Disorders
Samuel Klein

Danforth Professor of Medicine,
Department of Medicine,
Washington University School of Medicine,
St. Louis, Missouri
Obesity
David L. Kleinberg

Professor of Medicine and Director,
Neuroendocrine Research Medicine,
New York University School of Medicine;
Attending, Medicine, New York University Medical Center;
Consultant in Medicine, New York Harbor Healthcare Veterans Administration Hospital,
New York, New York
Anterior Pituitary
Barbara E. Kream

Professor, Departments of Medicine and Genetics and Developmental Biology,

University of Connecticut Health Center,
Farmington, Connecticut
Metabolic Bone Disease
Henry M. Kronenberg

Professor of Medicine,
Harvard Medical School;


Chief, Endocrine Unit,
Massachusetts General Hospital,
Boston, Massachusetts
Principles of Endocrinology;
Hormones and Disorders of Mineral Metabolism
Steven W. J. Lamberts

Professor of Medicine,
Erasmus University Rotterdam,
Rotterdam, The Netherlands
Endocrinology and Aging

XI

P. Reed Larsen

Professor of Medicine,
Harvard Medical School;
Chief, Division of Endocrinology, Diabetes and Hypertension,
and Senior Physician,
Brigham and Women's Hospital,

Boston, Massachusetts
Principles of Endocrinology;
Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid Disorders;
Thyrotoxicosis;
Hypothyroidism and Thyroiditis
Jennifer E. Lawrence

Director,
South Georgia Medical Center Diabetes Center;
Chief,
Division of Endocrinology,


South Georgia Medical Center,
Valdosta, Georgia
Endocrine Hypertension
Mitchell A. Lazar

Sylvan H. Eisman Professor of Medicine and Genetics and Director,
Penn Diabetes Center,
University of Pennsylvania School of Medicine;
Chief, Division of Endocrinology, Diabetes, and Metabolism,
Hospital of The University of Pennsylvania,
Philadelphia, Pennsylvania
Mechanism of Action of Hormones That Act on Nuclear Receptors
Joseph A. Lorenzo

Professor of Medicine,
University of Connecticut School of Medicine;
Attending Physician,

John Dempsey Hospital/University of Connecticut Health Center,
Farmington, Connecticut
Metabolic Bone Disease
Malcolm J. Low

Professor,
Department of Behavioral Neuroscience,
Oregon Health and Science University;
Scientist, Vollum Institute,
Oregon Health and Science University,
Portland, Oregon
Neuroendocrinology
Robert W. Mahley


Professor of Pathology and Medicine,
University of California, San Francisco;
Director, Gladstone Institute of Cardiovascular Disease,
San Francisco, California
Disorders of Lipid Metabolism

XII

Stephen J. Marx

Chief, Metabolic Diseases Branch,
and Chief, Genetics and Endocrinology Section,
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health,
Bethesda, Maryland

Multiple Endocrine Neoplasia
Shlomo Melmed

Senior Vice President,
Academic Affairs,
Cedars Sinai Medical Center;
Professor of Medicine and Associate Dean,
University of California, Los Angeles,
School of Medicine,
Los Angeles, California
Principles of Endocrinology;
Anterior Pituitary
Rebeca D. Monk