Harrison's Endocrinology, 3E

560 Pages·2013·25.717 MB·English

by  J. Jameson

3rd Edition
’ TM
HARRISON S
Endocrinology
Derived from Harrison’s Principles of Internal Medicine, 18th Edition
Editors
Dan L. Longo, anthony s. Fauci,
md md
Professor of Medicine, Harvard Medical School; Chief, Laboratory of Immunoregulation; Director,
Senior Physician, Brigham and Women’s Hospital; National Institute of Allergy and Infectious Diseases,
Deputy Editor, New England Journal of Medicine, National Institutes of Health, Bethesda, Maryland
Boston, Massachusetts
DEnnis L. KaspEr, stEphEn L. hausEr,
md md
William Ellery Channing Professor of Medicine, Robert A. Fishman Distinguished Professor and Chairman,
Professor of Microbiology and Molecular Genetics, Department of Neurology,
Harvard Medical School; Director, Channing Laboratory, University of California, San Francisco,
Department of Medicine, Brigham and Women’s Hospital, San Francisco, California
Boston, Massachusetts
J. Larry JamEson, , JosEph LoscaLzo, ,
md phd md phd
Robert G. Dunlop Professor of Medicine; Hersey Professor of the Theory and Practice of Medicine,
Dean, University of Pennsylvania School of Medicine; Harvard Medical School;
Executive Vice-President of the University of Pennsylvania for the Chairman, Department of Medicine;
Health System, Philadelphia, Pennsylvania Physician-in-Chief, Brigham and Women’s Hospital,
Boston, Massachusetts
3rd Edition
’
TM
HARRISON S
Endocrinology
EDitor
J. Larry Jameson, mD, phD
Robert G. Dunlop Professor of Medicine;
Dean, University of Pennsylvania School of Medicine;
Executive Vice-President of the University of Pennsylvania for the
Health System, Philadelphia, Pennsylvania
New York Chicago San Francisco Lisbon London Madrid Mexico City
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contents
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vii 13 Hirsutism and Virilization . . . . . . . . . . . . . . . .209
David A. Ehrmann
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
14 Gynecologic Malignancies . . . . . . . . . . . . . . . .215
1 Principles of Endocrinology . . . . . . . . . . . . . . . . .1
Michael V. Seiden
J. Larry Jameson
15 Sexual Dysfunction . . . . . . . . . . . . . . . . . . . . .224
Kevin T. McVary
section i
Pituitary, thyroid, and
adrenal disorders section iii
diabetes Mellitus, obesity,
2 Disorders of the Anterior Pituitary and
liPoProtein MetabolisM
Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . .16
Shlomo Melmed, J. Larry Jameson 16 Biology of Obesity . . . . . . . . . . . . . . . . . . . . .234
Jeffrey S. Flier, Eleftheria Maratos-Flier
3 Disorders of the Neurohypophysis . . . . . . . . . . .50
Gary L. Robertson 17 Evaluation and Management of Obesity . . . . . .244
Robert F. Kushner
4 Disorders of the Thyroid Gland . . . . . . . . . . . . .62
J. Larry Jameson, Anthony P. Weetman 18 The Metabolic Syndrome . . . . . . . . . . . . . . . .253
Robert H. Eckel
5 Disorders of the Adrenal Cortex . . . . . . . . . . . .100
Wiebke Arlt 19 Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . .261
Alvin C. Powers
6 Pheochromocytoma. . . . . . . . . . . . . . . . . . . . .127
Hartmut P. H. Neumann 20 Hypoglycemia . . . . . . . . . . . . . . . . . . . . . . . . .308
Philip E. Cryer, Stephen N. Davis
section ii 21 Disorders of Lipoprotein Metabolism . . . . . . . .317
reProductive endocrinology Daniel J. Rader, Helen H. Hobbs
7 Disorders of Sex Development . . . . . . . . . . . . .136
John C. Achermann, J. Larry Jameson section iV
disorders affecting MultiPle
8 Disorders of the Testes and Male Reproductive
endocrine systeMs
System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .148
Shalender Bhasin, J. Larry Jameson 22 Endocrine Tumors of the Gastrointestinal
Tract and Pancreas . . . . . . . . . . . . . . . . . . . . . .342
9 Testicular Cancer . . . . . . . . . . . . . . . . . . . . . .172
Robert T. Jensen
Robert J. Motzer, George J. Bosl
23 Disorders Affecting Multiple Endocrine
10 The Female Reproductive System, Infertility,
Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .363
and Contraception . . . . . . . . . . . . . . . . . . . . . .178
Camilo Jimenez Vasquez, Robert F. Gagel
Janet E. Hall
24 Endocrine Paraneoplastic Syndromes . . . . . . . .375
11 Menstrual Disorders and Pelvic Pain . . . . . . . . .194
J. Larry Jameson
Janet E. Hall
12 The Menopause Transition and
Postmenopausal Hormone Therapy . . . . . . . . .200
JoAnn E. Manson, Shari S. Bassuk
v
vi Contents
section V 29 Paget’s Disease and Other Dysplasias
disorders of bone and of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .459
calciuM MetabolisM Murray J. Favus, Tamara J. Vokes
25 Bone and Mineral Metabolism in Appendix
Laboratory Values of Clinical Importance .......471
Health and Disease . . . . . . . . . . . . . . . . . . . . .384
Alexander Kratz, Michael A. Pesce,
F. Richard Bringhurst, Marie B. Demay,
Robert C. Basner, Andrew J. Einstein
Stephen M. Krane, Henry M. Kronenberg
Review and Self-Assessment . . . . . . . . . . . . . . .487
26 Hypercalcemia and Hypocalcemia . . . . . . . . . .402
Charles Wiener, Cynthia D. Brown,
Sundeep Khosla
Anna R. Hemnes
27 Disorders of the Parathyroid Gland and
Calcium Homeostasis . . . . . . . . . . . . . . . . . . . .406
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .527
John T. Potts, Jr., Harald Jüppner
28 Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . .439
Robert Lindsay, Felicia Cosman
contributors
Numbers in brackets refer to the chapter(s) written or co-written by the contributor.
John C. Achermann, MD, PhD Robert H. Eckel, MD
Wellcome Trust Senior Fellow, UCL Institute of Child Health, Professor of Medicine, Division of Endocrinology,
University College London, London, United Kingdom [7] Metabolism, and Diabetes and Division of Cardiology;
Professor of Physiology and Biophysics, Charles A. Boettcher,
Wiebke Arlt, MD, DSc, FRCP, FMedSci II Chair in Atherosclerosis, University of Colorado
Professor of Medicine, Centre for Endocrinology, Diabetes and School of Medicine; Director, Lipid Clinic,
Metabolism, School of Clinical and Experimental Medicine, University of Colorado Hospital, Aurora, Colorado [18]
University of Birmingham; Consultant Endocrinologist,
University Hospital Birmingham, Birmingham, United Kingdom [5] David A. Ehrmann, MD
Professor of Medicine, University of Chicago, Chicago, Illinois [13]
Robert C. Basner, MD
Professor of Clinical Medicine, Division of Pulmonary, Allergy, and Andrew J. Einstein, MD, PhD
Critical Care Medicine, Columbia University College of Physicians Assistant Professor of Clinical Medicine, Columbia University College
and Surgeons, New York, New York [Appendix] of Physicians and Surgeons; Department of Medicine, Division of
Cardiology, Department of Radiology, Columbia University Medical
Shari S. Bassuk, ScD Center and New York-Presbyterian Hospital, New York, New York
Epidemiologist, Division of Preventive Medicine, Brigham and [Appendix]
Women’s Hospital, Boston, Massachusetts [12]
Murray J. Favus, MD
Shalender Bhasin, MD Professor, Department of Medicine, Section of Endocrinology,
Professor of Medicine; Section Chief, Division of Endocrinology, Diabetes, and Metabolism; Director, Bone Program, University of
Diabetes, and Nutrition, Boston University School of Medicine, Chicago Pritzker School of Medicine, Chicago, Illinois [29]
Boston, Massachusetts [8]
Jeffrey S. Flier, MD
George J. Bosl, MD Caroline Shields Walker Professor of Medicine and Dean, Harvard
Professor of Medicine, Weill Cornell Medical College; Chair, Medical School, Boston, Massachusetts [16]
Department of Medicine; Patrick M. Byrne Chair in Clinical
Oncology, Memorial Sloan-Kettering Cancer Center, New York, Robert F. Gagel, MD
New York [9] Professor of Medicine and Head, Division of Internal Medicine,
University of Texas MD Anderson Cancer Center, Houston, Texas [23]
F. Richard Bringhurst, MD
Associate Professor of Medicine, Harvard Medical School; Janet E. Hall, MD, MSc
Physician, Massachusetts General Hospital, Boston, Massachusetts [25] Professor of Medicine, Harvard Medical School; Associate Physician,
Massachusetts General Hospital, Boston, Massachusetts [10, 11]
Cynthia D. Brown, MD
Assistant Professor of Medicine, Division of Pulmonary and Critical Anna R. Hemnes, MD
Care Medicine, University of Virginia, Charlottesville, Virginia Assistant Professor, Division of Allergy, Pulmonary, and Critical
[Review and Self-Assessment] Care Medicine, Vanderbilt University Medical Center, Nashville,
Tennessee [Review and Self-Assessment]
Felicia Cosman, MD
Professor of Clinical Medicine, Columbia University College of Helen H. Hobbs, MD
Physicians and Surgeons, New York [28] Professor of Internal Medicine and Molecular Genetics, University
of Texas Southwestern Medical Center, Dallas, Texas; Investigator,
Philip E. Cryer, MD Howard Hughes Medical Institute, Chevy Chase, Maryland [21]
Irene E. and Michael M. Karl Professor of Endocrinology and
Metabolism in Medicine, Washington University School of Medicine; J. Larry Jameson, MD, PhD
Physician, Barnes-Jewish Hospital, St. Louis, Missouri [20] Robert G. Dunlop Professor of Medicine; Dean, University of
Pennsylvania School of Medicine; Executive Vice President of the
Stephen N. Davis, MBBS, FRCP University of Pennsylvania for the Health System, Philadelphia,
Theodore E. Woodward Professor and Chairman, Pennsylvania [1, 2, 4, 7, 8, 24]
Department of Medicine, University of Maryland
School of Medicine; Physician-in-Chief, University of Maryland Robert T. Jensen, MD
Medical Center, Baltimore, Maryland [20] Digestive Diseases Branch, National Institute of Diabetes;
Digestive and Kidney Diseases, National Institutes of Health,
Marie B. Demay, MD Bethesda, Maryland [22]
Professor of Medicine, Harvard Medical School; Physician,
Massachusetts General Hospital, Boston, Massachusetts [25]
vii
viii Contributors
Harald Jüppner, MD Hartmut P. H. Neumann, MD
Professor of Pediatrics, Endocrine Unit and Pediatric Nephrology Head, Section of Preventative Medicine, Department of Nephrol-
Unit, Massachusetts General Hospital, Boston, Massachusetts [27] ogy and General Medicine, Albert-Ludwigs-University of Freiburg,
Germany [6]
Sundeep Khosla, MD
Professor of Medicine and Physiology, College of Medicine, Michael A. Pesce, PhD
Mayo Clinic, Rochester, Minnesota [26] Professor Emeritus of Pathology and Cell Biology,
Columbia University College of Physicians and Surgeons;
Stephen M. Krane, MD Columbia University Medical Center, New York,
Persis, Cyrus, and Marlow B. Harrison Distinguished Professor of New York [Appendix]
Medicine, Harvard Medical School; Massachusetts General Hospital,
Boston, Massachusetts [25] John T. Potts, Jr., MD
Director of Research, Massachusetts General Hospital,
Alexander Kratz, MD, PhD, MPH Boston, Massachusetts [27]
Associate Professor of Pathology and Cell Biology,
Columbia University College of Physicians and Surgeons; Alvin C. Powers, MD
Director, Core Laboratory, Columbia University Medical Center, Joe C. Davis Chair in Biomedical Science; Professor of Medicine,
New York, New York [Appendix] Molecular Physiology, and Biophysics; Director, Vanderbilt Diabetes
Center; Chief, Division of Diabetes, Endocrinology, and Metabolism,
Henry M. Kronenberg, MD Vanderbilt University School of Medicine, Nashville, Tennessee [19]
Professor of Medicine, Harvard Medical School;
Chief, Endocrine Unit, Massachusetts General Hospital, Daniel J. Rader, MD
Boston, Massachusetts [25] Cooper-McClure Professor of Medicine and Pharmacology, University
of Pennsylvania School of Medicine, Philadelphia, Pennsylvania [21]
Robert F. Kushner, MD, MS
Professor of Medicine, Northwestern University Gary L. Robertson, MD
Feinberg School of Medicine, Chicago, Illinois [17] Senior Research Scientist and Staff Physician, Henry Ford Hospital,
Detroit, Michigan [3]
Robert Lindsay, MD, PhD
Chief, Internal Medicine; Professor of Clinical Medicine, Michael V. Seiden, MD, PhD
Helen Hayes Hospital, West Haverstraw, New York [28] Professor of Medicine; President and CEO,
Fox Chase Cancer Center, Philadelphia, Pennsylvania [14]
JoAnn E. Manson, MD, DrPH
Professor of Medicine and the Michael and Lee Bell Camilo Jimenez Vasquez, MD
Professor of Women’s Health, Harvard Medical School; Assistant Professor, Department of Endocrine Neoplasia and Hormonal
Chief, Division of Preventive Medicine, Brigham and Women’s Disorders, Division of Internal Medicine, University of Texas MD
Hospital, Boston, Massachusetts [12] Anderson Cancer Center, Houston, Texas [23]
Eleftheria Maratos-Flier, MD Tamara J. Vokes, MD, FACP
Associate Professor of Medicine, Harvard Medical School; Professor, Department of Medicine, Section of Endocrinology,
Division of Endocrinology, Beth Israel Deaconess Medical Center, University of Chicago, Chicago, Illinois [29]
Boston, Massachusetts [16]
Anthony P. Weetman, MD
Kevin T. McVary, MD, FACS University of Sheffield School of Medicine, Sheffield,
Professor of Urology, Department of Urology, United Kingdom [4]
Northwestern University Feinberg School of Medicine,
Chicago, Illinois [15] Charles M. Wiener, MD
Dean/CEO Perdana University Graduate School of Medicine,
Shlomo Melmed, MD Selangor, Malaysia; Professor of Medicine and Physiology,
Senior Vice President and Dean of the Medical Faculty, Johns Hopkins University School of Medicine,
Cedars-Sinai Medical Center, Los Angeles, California [2] Baltimore, Maryland [Review and Self-Assessment]
Robert J. Motzer, MD
Professor of Medicine, Weill Cornell Medical College;
Attending Physician, Genitourinary Oncology Service,
Memorial Sloan-Kettering Cancer Center, New York, New York [9]
Preface
Harrison’s Principles of Internal Medicine has been a respected Obesity, Lipoprotein Metabolism; (IV) Disorders Affect-
information source for more than 60 years. Over time, ing Multiple Endocrine Systems; and (V) Disorders of
the traditional textbook has evolved to meet the needs of Bone and Calcium Metabolism.
internists, family physicians, nurses, and other health care While Harrison’s Endocrinology is classic in its organiza-
providers. The growing list of Harrison’s products now tion, readers will sense the impact of the scientific re-
includes Harrison’s for the iPad, Harrison’s Manual of Medi- naissance as they explore the individual chapters in each
cine, and Harrison’s Online. This book, Harrison’s Endocrinol- section. In addition to the dramatic advances emanating
ogy, now in its third edition, is a compilation of chapters from genetics and molecular biology, the introduction of
related to the specialty of endocrinology. an unprecedented number of new drugs, particularly for
Our readers consistently note the sophistication of the the management of diabetes and osteoporosis, is trans-
material in the specialty sections of Harrison’s. Our goal forming the field of endocrinology. Numerous recent
was to bring this information to readers in a more com- clinical studies involving common diseases like diabetes,
pact and usable form. Because the topic is more focused, obesity, hypothyroidism, and osteoporosis provide pow-
it was possible to increase the presentation of the mate- erful evidence for medical decision making and treat-
rial by enlarging the text and the tables. We have also ment. These rapid changes in endocrinology are exciting
included a Review and Self-Assessment section that in- for new students of medicine and underscore the need
cludes questions and answers to provoke reflection and for practicing physicians to continuously update their
to provide additional teaching points. knowledge base and clinical skills.
The clinical manifestations of endocrine disorders Our access to information through web-based journals
can usually be explained by considering the physiologic and databases is remarkably efficient. While these sources
role of hormones, which are either deficient or exces- of information are invaluable, the daunting body of data
sive. Thus, a thorough understanding of hormone action creates an even greater need for synthesis and for high-
and principles of hormone feedback arms the clinician lighting important facts. Thus, the preparation of these
with a logical diagnostic approach and a conceptual chapters is a special craft that requires the ability to distill
framework for treatment approaches. The first chapter core information from the ever-expanding knowledge
of the book, Principles of Endocrinology, provides this base. The editors are therefore indebted to our authors,
type of “systems” overview. Using numerous examples a group of internationally recognized authorities who are
of translational research, this introduction links genet- masters at providing a comprehensive overview while
ics, cell biology, and physiology with pathophysiology being able to distill a topic into a concise and interesting
and treatment. The integration of pathophysiology with chapter. We are indebted to our colleagues at McGraw-
clinical management is a hallmark of Harrison’s, and can Hill. Jim Shanahan is a champion for Harrison’s, and these
be found throughout each of the subsequent disease- books were impeccably produced by Kim Davis.
oriented chapters. The book is divided into five main We hope you find this book useful in your effort to
sections that reflect the physiologic roots of endocri- achieve continuous learning on behalf of your patients.
nology: (I) Pituitary, Thyroid, and Adrenal Disorders;
(II) Reproductive Endocrinology; (III) Diabetes Mellitus, J. Larry Jameson, MD, PhD
ix