Oxford American Handbook of Endocrinology and Diabetes Draznin_Prelims.indd i 4/2/2011 6:51:22 PM About the Oxford American Handbooks in Medicine The Oxford American Handbooks are pocket cl inical books, providing practi- cal guidance in quick reference, note form. Titles cover ma jor medical special- ties or cross-specialty topics and are aimed at students, residents, i nternists, family physicians, and practicing physicians within speci \201 c disciplines. Their reputation is built on including the best clinical information, com- plemented by hin ts, tips, and advice from the authors. Each one is carefully reviewed by senior subject exp erts, residents, and students to ensure that content re \202 ects the reality of day-to-da y medical practice. Key series features \200 Written in short chunks, each topic is covered in a two-page spr ead to enable readers to \201 nd information quickly. They are also perfect for test prep aration and gaining a quick overview of a subject without scanning through unnecessary page s. Content is evidence based and complemented by the expertise and judgment of experienced authors. The Handbooks provide a humanistic approach to medicine \200\224it \200\231s more than just treatment by numbers. A \200\234friend in your pocket, \200\235 the Handbooks offer honest, reliable guidance ab out the dif \201 culties of practicing medicine and provide coverage of both the practice and art of medicine. For quick reference, useful \200\234everyday \200\235 information is included on the inside covers. Published and Upcoming Oxford American Handbooks Oxford American Handbook of Clinical Medic ine Oxford American Handbook of Anesthesiology Oxford American Handbook of Cardiology Oxfor d American Handbook of Clinical Dentistry Oxford American Handbook of Clinical Diagnosis Ox ford American Handbook of Clinical Examination and Practical Skills Oxford American Handboo k of Clinical Drugstore Oxford American Handbook of Critical Care Oxford American Handbook of Emergency Medicine Oxford American Handbook of Endocrinology and Diabetes Oxford America n Handbook of Gastroenterology and Hepatology Oxford American Handbook of Geriatric Medicin e Oxford American Handbook of Nephrology and Hypertension Oxford American Handbook of Neuro logy Oxford American Handbook of Obstetrics and Gynecology Oxford American Handbook of Onco logy Oxford American Handbook of Ophthalmology Oxford American Handbook of Otolaryngology O xford American Handbook of Pediatrics Oxford American Handbook of Physical Medicine and Reh abilitation Oxford American Handbook of Psychiatry Oxford American Handbook of Pulmonary Me dicine Oxford American Handbook of Rheumatology Oxford American Handbook of Sports Medicine Oxford American Handbook of Surgery Oxford American Handbook of Urology Draznin_Prelims.indd ii 4/2/2011 6:51:22 PM Oxford American Handbook of Endocrinology and Diabetes Edited by B oris D raznin, MD, PhD Director, Adult Diabetes Program Professor of Medicine D ivision of Endocrinology, Metabolism and Diabetes University of Colorado School of Medicine Aurora, Colorado S ol E pstein, MD Professor of Medicine and Geriatrics Mount Sinai School of Medicine New York, NY with H elen E. T urner J ohn A.H. W ass 1 Draznin_Prelims.indd iii 4/2/2011 6:51:22 PM 3 Oxford University Press, Inc. publishes works that further Oxford University \200\231s obje ctive of excellence in research, scholarship and education. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico Cit y Nairobi New Delhi Shanghai Taipei Toronto With of \201 ces in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan P oland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Copyright 2011 by Oxford University Press, Inc. Published by Oxford University Press Inc. 198 Madison Avenue, New York, New York 10016 www.oup.com Oxford is a registered trade mark of Oxford University Press First published 2011 UK version published: 2009 All rights reserved. No part of this publication may be reproduced, stored in a retrieval s ystem, or transmitted, in any form or by any means, electronic, mechanical, photocopying, r ecording, or otherwise, without the prior permission of Oxford University Press, Library of Congress Cataloging-in-Publication Data Oxford American handbook of endocrinology and diabetes / edited by Boris Draznin \200 [et al.]. p. ; cm. Handbook of endocrinology and diabetes Includes bibliographical references and index. ISBN 978-0-19-537428-5 1. Endocrinology \200\224Handbooks, manuals, etc. 2. Diab etes \200\224Handbooks, manuals, etc. [DNLM: 1. Endocrine System Diseases \200\224Handbooks . 2. Diabetes Mellitus \200\224Handbooks. WK 39] RC649.O94 2011 616.4 \200\224dc22 20100509 77 I. Draznin, Boris. II. Title: Handbook of endocrinology and diabetes. 10 9 8 7 6 5 4 3 2 1 Printed in China on acid-free paper Draznin_Prelims.indd iv 4/2/2011 6:51:22 PM This material is not intended to be, and should not be considered, a sub- stitute for medic al or other professional advice. Treatment for the con- ditions described in this material is highly dependent on the individual circumstances. And, while this material is designed t o offer accurate infor- mation with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about medical and health issues is c onstantly evolving and dose schedules for medications are being revised continually, with n ew side effects recognized and accounted for regularly. Readers must therefore always check the product informa- tion and clinical procedures with the most up-to-date published prod- uct information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation. Oxford University Press and the authors make no representat ions or warranties to readers, express or implied, as to the accuracy or completeness of th is material, including without limitation that they make no representation or warran- ties as to the accuracy or ef \201 cacy of the drug dosages mentioned in the material. The auth ors and the publishers do not accept, and expressly disclaim, any responsibility for any li ability, loss, or risk that may be claimed or incurred as a consequence of the use and/or a pplication of any of the contents of this material. Draznin_Prelims.indd v 4/2/2011 6:51:22 PM vi Preface In this era of rapid electronic transfer of medical information, the ques- tion is often po sed: \200\234Do we need textbooks anymore, as by the time they are printed much of the inf ormation is outdated? \200\235 This question is best answered by this publication, which of fers the reader current, practical, clinical evidence \200\223based information that will b ene \201 t patients with endo- crine and metabolic disease. This handbook is not meant to be a fully comprehensive tome but to act as a quick and easily accessible source of informa tion. While we have endeavored to include material that is as current as pos- sible, the many adv ances occurring in the \201 eld of endocrinology and dia- betes made this a daunting task . This meant including emerging advances in translational research, molecular biology, geno mics, diagnostic tests, and therapies without sacri \201 cing clinical presentations. Our expert colleagues, to whom we as co-editors are eternally indebted and who are too nume rous to mention individually, have devoted a con- siderable amount of time to ensuring the provision of the most relevant information in a very readable fashion. They accepted their assignments with grace and a willingness to participate, which made our task as editors so much easier. We are certain that the reader will enjoy this U.S. version of the Oxford Hand book of Endocrinology and Diabetes and apply this to their clinical practice. We thank the authors of the original British edition, Helen E. Turner and John A.H. Wass. W e also thank the editorial staff of the Oxford University Press for their professional assi stance. Boris Draznin and Sol Epstein Draznin_Prelims.indd vi 4/2/2011 6:51:22 PM vii Contents Contributors viii Detailed contents ix Symbols and abbreviations xxviii Part 1 Part 2 Part 3 Part 4 Part 5 Part 6 Part 7 Part 8 Part 9 Thyroid Pituitary Adrenals Reproductive endocrinology Endocrine disorders of pregnancy Calc ium and bone metabolism Pediatric endocrinology Neuroendocrine disorders Inherited endocrin e syndromes and multiple endocrine neoplasia (MEN) 1 81 163 221 345 365 429 463 485 513 585 659 687 Part 10 Miscellaneous endocrinology Part 11 Diabetes Part 12 Lipids and hyperlipidemia Part 13 Laboratory endocrinology Index 699 Draznin_Prelims.indd vii 4/2/2011 6:51:22 PM viii Contributors Marc-Andre Cornier, MD Associate Professor of Medicine Division of Endocrinology, Kristen Nadeau, MS, MD Assistant Professor of Pediatrics Division of Pediatric Endocrinolog y Metabolism and Diabetes University of Colorado School of University of Colorado School Medicine Aurora, CO Part : Miscellaneous Endocrinology of Medicine Aurora, CO Part : Pediatric Endocrinology Rachel Pessah, MD Division of Endocrinology, Emily Gallagher, MB, BCh, BAO Diabetes, and Bone Disease Mount Sinai School of Medicine New York, NY Part : Thyroid Division of Endocrinology, Diabetes, and Bone Disease Mount Sinai School of Medicine New York, NY Part : Neuroendocrin e Disorders E. Chester Ridgway, MD Professor of Medicine Senior Associate Dean for Dina Green, MD Assistant Professor of Medicine Division of Endocrinology, Academic Affairs Vise Chairman: Department of Medicine Diabetes, and Bone Disease Mount Sinai School of Medicine New York, NY Parts : Thyroid, Neu roendocrine University of Colorado School of Medicine Aurora, CO Part : Laboratory Endocrinology Disorders, Lipids and Hyperlipidemia Barrie Weinstein, MD Division of Endocrinology, Janice M. Kerr, MD Assistant Professor Division of Endocrinology, Diabetes, and Bone Disease Mount Sinai School of Medicine New York, NY Part : Lipids and Hy perlipidemia Metabolism and Diabetes University of Colorado Denver/ Anschutz Medical Campus Margaret E. Wierman, MD Chief of Endocrinology, Denver Aurora, CO Part : Pituitary VAMC Caroline Messer, MD Division of Endocrinology, Professor of Medicine, Physiology and Biophysics University of Colorado School Diabetes, and Bone Disease Mount Sinai School of Medicine New York, NY Part : Thyroid of Medicine Aurora, CO Part : Reproductive Endocrinology Draznin_Prelims.indd viii 4/2/2011 6:51:22 PM ix Detailed contents Part 1 Thyroid 1 Anatomy and physiology of the thyroid 2 Anatomy 2 Physiology 4 2 Thyroid investigations 7 Tests of hormone concentration 7 Tests of homeostatic control 7 Antibody screen 10 Scintisc anning 11 Ultrasound (US) scanning 13 Fine needle aspiration (FNAC) cytology 14 Computed to mography (CT) 14 Additional laboratory investigations 15 Sick euthyroid syndrome (non-thyro idal illness syndrome) 15 Atypical clinical situations 16 3 Thyrotoxicosis 17 Etiology 17 Manifestations of hyperthyroidism 19 Treatment 21 Thyroid crisis (storm) 28 Thy rotoxicosis in pregnancy 31 Hyperthyroidism in children 35 Secondary hyperthyroidism 36 4 Graves \200\231 ophthalmopathy, dermopathy, and acropachy 39 Graves \200\231 ophthalmopathy 39 Graves \200\231 dermopathy 43 Thyroid acropachy 43 5 Multinodular goiter and solitary adenomas 44 Background 44 Clinical evaluation 45 Studies 46 Treatment 47 Pathology 48 Thyroid nodules i n pregnant mothers 48 Draznin_Prelims.indd ix 4/2/2011 6:51:22 PM DETAILED CONTENTS DETAILED CONTENTS x 6 Thyroiditis 49 Background 49 Chronic autoimmune thyroiditis 50 Other types of thyroiditis 51 7 Hypothyroidism 53 Background 53 Clinical picture 55 Treatment of hypothyroidism 56 Treatment of subclinical h ypothyroidism 57 Management of myxedema coma 58 Congenital hypothyroidism 60 8 Amiodarone and thyroid function 62 Background 62 Pathogenesis 63 Diagnosis and treatment 64 9 Thyroid cancer 66 Epidemiology 66 Etiology 67 Papillary thyroid carcinoma 68 Staging of DTC 69 Surgery 70 Pos toperative thyroid hormone therapy 70 Radioactive iodine therapy 71 Management of recurrent disease 74 Follicular thyroid carcinoma (FTC) 75 Follow-up of papillary and follicular thy roid carcinoma 76 Medullary thyroid carcinoma (MTC) 78 Anaplastic (undifferentiated) thyroi d cancer 79 Lymphoma 79 Part 2 Pituitary 10 Pituitary gland anatomy and physiology 82 Embryology and anatomy 82 Anterior gland physiology 83 Posterior gland physiology 85 11 Imaging 86 Background 86 MRI appearances 86 Pituitary adenomas 87 Craniopharyngiomas/Rathke \200\231s cleft cyst 88 Draznin_Prelims.indd x 4/2/2011 6:51:22 PM DETAILED CONTENTS xi 12 Pituitary function testing 89 Background 89 Lactotropes 89 Thyrotropes 89 Gonadotropes 90 Corticotropes 91 Somatotropes 9 3 13 Hypopituitarism 94 De \201 nition 94 Etiologies of hypopituitarism 94 Features 95 Investigations 97 Treatment 97 14 Anterior pituitary hormone replacement 98 Background 98 Glucocorticoids replacement 98 Growth hormone replacement 99 Thyroid hormone replacement 100 Sex hormone replacement 100 15 Pituitary tumor basics 101 Epidemiology 101 Classi \201 cation 101 Pathophysiology 102 Investigations 102 Management and natural history 103 16 Prolactinomas 104 Epidemiology 104 Etiology and pathogenesis 104 Clinical features 104 Investigations 106 Hyp erprolactinemia and drugs 106 Idiopathic hyperprolactinemia 106 Treatment 107 Management of prolactinomas in pregnancy 109 17 Acromegaly 110 De \201 nition 110 Epidemiology 110 Etiologies of acromegaly 110 Pathophysiology 110 Clini cal features 110 Investigations 112 Management 114 Mortality data 115 Draznin_Prelims.indd xi 4/2/2011 6:51:23 PM DETAILED CONTENTS xii 18 Cushing \200\231s disease 116 De \201 nition 116 Epidemiology 116 Differential diagnosis 116 Etiologies of CS 116 Clinic al features of CS 117 Investigations 118 Treatment 122 Follow-up 124 19 Gonadotropinomas 125 Epidemiology 125 Pathology 125 Clinical features 125 Investigations 126 Management 126 Foll ow-up and prognosis 126 20 Thyrotropinomas 128 Epidemiology 128 Clinical features 128 Investigations 128 Management 128 21 Craniopharyngiomas and Rathke \200\231s cleft cysts 130 Craniopharyngiomas 130 Epidemiology 130 Pathology 130 Clinical features 130 Investigations 131 Management 131 Follow-up 131 Rathke \200\231s cleft cysts (RCC) 132 Epidemiology 132 Pa thology 132 Clinical features 132 Investigations 132 Management 132 Follow-up 133 22 Parasellar tumors 134 Meningiomas 134 Germ cell tumor (GCT) 134 Gangliocytomas 134 Chordomas/condrosarcomas 135 H amartomas 135 Metastatic tumors to the pituitary 135 Draznin_Prelims.indd xii 4/2/2011 6:51:23 PM DETAILED CONTENTS xiii 23 In \202 ammatory and in \201 ltrative pituitary diseases 136 Background 136 Investigations 137 Lymphocytic hypophysitis 137 Sarcoidosis 138 Langerhans \200\231 cell histiocytosis 139 Hemochromatosis 139 24 Surgical treatment of pituitary tumors 140 Transsphenoidal surgery (TSS) 140 Transfrontal craniotomy 143 25 Medical treatment of pituitary tumors 144 Dopamine agonists (DA) 144 Somatostatin analogs 145 Growth hormone receptor antagonists 146 26 Pituitary radiotherapy 147 Background 147 Techniques 147 Ef \201 cacy 148 Complications 149 27 Diabetes insipidus (DI) 151 De \201 nition 151 Classi \201 cation and etiologies 151 Features 152 Investigations 153 Treatment 154 Caveats for water deprivation study 155 28 Hyponatremia 156 Incidence 156 Etiologies 156 Neurosurgical hyponatremia 157 Classi \201 cation and clinica l features 157 Investigations 158 Hyponatremia treatment 158 29 Syndrome of inappropriate ADH (SIADH) 159 De \201 nition 159 Features 159 Criteria for diagnosis 159 Types of SIADH 159 Treatment 16 0 Draznin_Prelims.indd xiii 4/2/2011 6:51:23 PM DETAILED CONTENTS xiv 30 Pineal gland 161 Physiology 161 Pineal and intracranial germ cell tumors 161 Features 161 Investigations and staging 161 Management 162 Prognosis 162 Part 3 Adrenals 31 Anatomy and physiology 164 Anatomy 164 Physiology 166 32 Imaging 168 Computed tomography (CT) scanning 168 Magnetic resonance imaging (MRI) 168 Ultrasound (US) imaging 168 Normal adrenal 169 Radionucleotide imaging 169 Positron emission tomography (PE T) 169 Venous sampling 169 33 Mineralocorticoid excess 170 De \201 nitions 170 34 Primary aldosteronism 171 Epidemiology 171 Pathophysiology 171 Clinical features 171 Conn \200\231s syndrome \200\224 aldosterone-producing adenoma 171 Bilateral adrenal hyperplasia (bilateral idiopathic hyperaldosteronism) 173 Glucocorticoid-remedial aldosteronism (GRA) 173 Aldosterone-producing carcinoma 173 Screeni ng 174 Con \201 rmation of diagnosis 176 Localization and con \201 rmation of differentia l diagnosis 179 Treatment 180 35 Excess other mineralocorticoids 182 Epidemiology 182 Apparent mineralocorticoid excess 182 Licorice ingestion 183 Ectopic ACTH syndrome 183 Deoxycorticosterone (DOC) excess 183 Draznin_Prelims.indd xiv 4/2/2011 6:51:23 PM DETAILED CONTENTS xv 36 Adrenal Cushing \200\231s syndrome 184 De \201 nition and epidemiology 184 Pathophysiology 184 Clinical features 185 Investigatio ns 185 Treatment 186 Prognosis 186 Subclinical Cushing \200\231s syndrome 187 37 Adrenal surgery 188 Adrenalectomy 188 38 Renal tubular abnormalities 190 Background 190 Liddle \200\231s syndrome 190 Bartter \200\231s syndrome 191 39 Mineralocorticoid de \201 ciency 192 Epidemiology 192 Causes 192 Treatment 192 40 Adrenal insuf \201 ciency 193 De \201 nition 193 Epidemiology 194 Pathophysiology 195 41 Addison \200\231s disease 196 Causes of primary adrenal insuf \201 ciency 196 Autoimmune adrenalitis 197 Clinical featur es 198 Autoimmune polyglandular syndrome (APS) type 1 198 APS types 2 \200\2234 199 Investi gation of primary adrenal insuf \201 ciency 200 Treatment 203 42 Long-term glucocorticoid administration 206 Short-term steroids 206 Steroid cover 206 Long-term steroids 207 Cushing \200\231s syndrome 207 43 Adrenal incidentalomas 208 De \201 nition and epidemiology 208 Importance 208 Draznin_Prelims.indd xv 4/2/2011 6:51:23 PM DETAILED CONTENTS xvi Differential diagnosis of an incidentally detected adrenal nodule 208 Investigations 209 Management 209 44 Pheochromocytomas and paragangliomas 210 De \201 nition 210 Incidence 210 Epidemiology 210 Pathophysiology 212 Clinical features 21 3 Complications 213 Investigations 214 Management 218 Part 4 Reproductive endocrinology 45 Hirsutism 222 De \201 nition 222 Physiology of hair growth 222 Androgen production in women 223 Evaluati on 224 46 Polycystic ovary syndrome (PCOS) 227 De \201 nition 227 Epidemiology 227 Other causes of hyperandrogenic anovulation 228 Featur es 230 Laboratory evaluation 232 Management 234 47 Congenital adrenal hyperplasia (CAH) in adults 239 De \201 nition 239 Epidemiology 239 Pathogenesis 239 Biochemistry 240 Clinical presentatio n 241 Laboratory evaluation 242 Management 244 Monitoring of treatment 246 Prognosis 247 48 Androgen-secreting tumors 249 De \201 nition 249 Epidemiology and pathology 249 Clinical features 250 Draznin_Prelims.indd xvi 4/2/2011 6:51:23 PM DETAILED CONTENTS xvii Laboratory evaluation 250 Management 251 Prognosis 251 49 Menstrual function disorders 252 De \201 nitions 252 Clinical evaluation 253 Laboratory evaluation 255 Management 256 50 Premature ovarian insuf \201 ciency (POI) 257 De \201 nition 257 Epidemiology 257 Pathogenesis 259 Clinical presentation 260 Laboratory evaluation 261 Management 262 Prognosis 263 51 Menopause 264 De \201 nition 264 Long-term consequences 266 Clinical presentation 266 Evaluation (if HRT is being considered) 267 Hormone replacement therapy (HT) 268 52 Oral contraceptive pill (OCP) 275 Introduction 275 Bene \201 ts 276 Risks 277 Practical issues 279 53 Testicular physiology 280 Anatomy 280 Regulation of testicular function 281 Physiology 283 54 Male hypogonadism 284 De \201 nition 284 Epidemiology 284 Secondary hypogonadism (hypogonadotropic hypogonadism) 285 Primary hypogonadism (hypergonadotropic hypogonadism) 289 Clinical assessment 293 Draznin_Prelims.indd xvii 4/2/2011 6:51:23 PM DETAILED CONTENTS xviii 55 Androgen therapy 296 Treatment goals 296 Indications for treatment 297 Risks and side effects 298 56 Gynecomastia 301 De \201 nition 301 Evaluation 303 Management 305 57 Erectile dysfunction 306 De \201 nition 306 Physiology of male sexual function 306 Pathophysiology 307 Evaluation 3 08 Management 311 58 Testicular tumors 314 Epidemiology 314 Risk factors 314 Prognosis 315 59 Infertility 316 De \201 nition 316 Causes 317 Evaluation 319 Management 324 Ovulation induction 328 60 Disorders of sexual differentiation 332 Clinical presentation 332 Evaluation 333 Androgen insensitivity syndrome 335 True hermaphro ditism 336 General principles of management 337 61 Transsexualism 339 De \201 nition 339 Epidemiology 339 Etiology 339 Management 340 Part 5 Endocrine disorders of pregnancy 62 Thyroid disorders 346 Normal physiology 346 Maternal hyperthyroidism 347 Draznin_Prelims.indd xviii 4/2/2011 6:51:23 PM DETAILED CONTENTS xix Maternal hypothyroidism 349 Postpartum thyroid dysfunction 350 Thyroid cancer in pregnancy 351 63 Pituitary disorders 352 Normal anatomical changes during pregnancy 352 Normal physiology during pregnancy 353 Prola ctinoma in pregnancy 354 Cushing \200\231s syndrome 356 Acromegaly 357 Hypopituitarism in p regnancy 358 64 Adrenal disorders during pregnancy 361 Normal changes during pregnancy 361 Addison \200\231s disease in pregnancy 362 Congenital a drenal hyperplasia 363 Pheochromocytoma 364 Part 6 Calcium and bone metabolism 65 Calcium and bone physiology 366 Bone turnover 366 Bone mass during life 367 Calcium 368 66 Investigation of bone 369 Bone turnover markers 369 Bone imaging 370 Bone mass measurements 371 Bone biopsy 372 67 Investigation of calcium, phosphate, and magnesium 373 Blood concentration 373 Urine excretion 374 Calcium-regulating hormones 375 68 Hypercalcemia 376 Epidemiology 376 Causes 376 Clinical features 377 Hyperparathyroidism 379 Treatment 382 Com plications of parathyroidectomy 384 Other causes of hypercalcemia 385 Familial hypocalciuri c hypercalcemia (FHH) 387 Vitamin D intoxication 387 Sarcoidosis 388 Draznin_Prelims.indd xix 4/2/2011 6:51:23 PM DETAILED CONTENTS xx 69 Hypocalcemia 389 Causes 389 Clinical features 391 Investigation 393 Treatment 394 70 Rickets and osteomalacia 396 De \201 nitions 396 Clinical features 396 Diagnosis 397 Vitamin D de \201 ciency 399 Hypo phosphatemia 401 71 Hypomagnesemia 403 Introduction 403 Treatment 404 72 Osteoporosis 405 Introduction 405 Pathology 406 Epidemiology 408 Presentation 409 Investigation 410 Treatmen t 413 Complications of therapy 417 73 Paget \200\231s disease 421 Pathology 421 Epidemiology 422 Clinical features 422 Investigation 423 Complications 424 Tr eatment 425 Monitoring therapy 426 74 Inherited disorders of bone 427 Osteogenesis imperfecta 427 Part 7 Pediatric endocrinology 75 Growth and stature 430 Growth 430 Short stature 434 Genetic short stature 436 Constitutional delay of growth and p uberty 436 Growth hormone de \201 ciency 437 Tall stature and rapid growth 445 Draznin_Prelims.indd xx 4/2/2011 6:51:23 PM DETAILED CONTENTS xxi 76 Puberty 447 Normal puberty 447 Precocious puberty 449 Delayed or absent puberty 453 77 Sexual differentiation 455 Normal sexual differentiation 455 Assessment of ambiguous genitalia 456 Disorders of sex de velopment (DSD) 457 Congenital adrenal hyperplasia 459 Part 8 Neuroendocrine disorders 78 The neuroendocrine system 464 Introduction 464 79 Carcinoid tumors 465 De \201 nition and classi \201 cation 465 Incidence 465 Carcinoid syndrome 466 Diagnostic investigations 467 Tumor localization and staging 468 Treatment 469 Prognosis 471 80 Insulinomas 472 De \201 nition 472 Incidence 472 Clinical presentation 472 Biochemical investigations 472 Tumor localization 473 Treatment 474 Prognosis 474 81 Gastrinomas 475 De \201 nition 475 Prevalence 475 Clinical presentation 475 Biochemical investigations 476 Treatment 477 82 Glucagonomas 478 De \201 nition 478 Incidence 478 Clinical presentation 478 Biochemical investigations 479 Draznin_Prelims.indd xxi 4/2/2011 6:51:23 PM DETAILED CONTENTS xxii Tumor localization 479 Treatment 480 83 VIPomas 481 De \201 nition 481 Clinical presentation 481 Biochemical investigations 482 Tumor localiza tion 482 Treatment 482 84 Somatostatinomas 483 De \201 nition 483 Clinical features 483 Biochemical investigations 484 Tumor localization 484 Treatment 484 Part 9 Inherited endocrine syndromes and multiple endocrine neoplasia (MEN) 85 McCune \200\223Albright syndrome 486 De \201 nition 486 Genetics 486 Clinical features 487 Prognosis 488 86 Neuro \201 bromatosis 489 De \201 nition 489 NF1 490 87 Von Hippel \200\223Lindau disease 492 De \201 nition 492 Genetics 493 Clinical features 494 Prognosis 495 88 Carney complex 496 De \201 nition 496 Genetics 496 Clinical presentation 496 89 Cowden syndrome 497 Incidence 497 Genetics 497 Clinical presentation 497 Draznin_Prelims.indd xxii 4/2/2011 6:51:23 PM DETAILED CONTENTS xxiii 90 POEMS syndrome 498 De \201 nition 498 Clinical presentation 498 Treatment 498 91 MEN type 1 499 De \201 nition 499 Genetics 499 Clinical features 499 Management 501 Mutational analysis 5 01 Screening 502 92 MEN type 2 503 De \201 nition 503 Genetics 503 Clinical features \200\224MEN2a 504 Clinical features \200 \224MEN2b 505 Management 505 Mutational analysis 506 Screening 506 93 Inherited primary hyperparathyroidism 507 Epidemiology 507 Causes 507 HPT-JT 507 FIHP 508 94 Inherited renal calculi 509 De \201 nition 509 Genetics 510 Management 511 Part 10 Miscellaneous endocrinology 95 Hypoglycemia 514 De \201 nition (Whipple \200\231s triad) 514 Epidemiology 515 Pathophysiology 516 Clinical features 517 Management 519 Postprandial reactive hypoglycemia (PRH) 520 96 Obesity 522 De \201 nition 522 Epidemiology 523 Etiology 524 Draznin_Prelims.indd xxiii 4/2/2011 6:51:23 PM DETAILED CONTENTS xxiv Pathophysiology 526 Consequences of obesity 527 Evaluation of an obese patient 528 Investig ations 529 Management 530 97 Endocrinology and aging 534 Introduction 534 Fluid and electrolyte homeostasis in the elderly 535 Bone disease 537 GH a nd IGF-1 in the elderly 538 Gonadal function in the elderly 539 Adrenal function in the eld erly 541 Thyroid disease 542 98 Endocrinology of critical illness 544 Endocrine dysfunction and AIDS 544 Cancer 549 Syndromes of ectopic hormone production 550 L iver disease 554 Renal disease 556 Endocrinology in the critically ill 558 99 Perioperative management of endocrine patients 561 Transsphenoidal surgery/craniotomy 561 Thyroidectomy 564 Parathyroidectomy 565 Pheochromocy toma 567 100 Syndromes of hormone resistance 569 De \201 nition 569 Thyroid hormone resistance 569 Androgen resistance 569 Glucocorticoid r esistance 569 ACTH resistance 570 Mineralocorticoid resistance 570 Differential diagnosis o f possible manifestations of endocrine disorders 571 101 Stress and the endocrine system 575 De \201 nition 575 Endocrine effects of stress 576 Metabolism 576 102 Alternative or complementary therapy and endocrinology 577 Introduction 577 Alternative therapy used in patients with diabetes mellitus 578 Draznin_Prelims.indd xxiv 4/2/2011 6:51:24 PM DETAILED CONTENTS xxv Alternative therapy used in menopause 580 Alternative therapy used by patients with osteoporosis 582 Miscellaneous 584 Part 11 Diabetes 103 Classi \201 cation and diagnosis 586 Background 586 Diagnosis 586 Classi \201 cation 587 Genetics 590 104 General management and treatment 593 Background 593 Assessment of the newly diagnosed patient 594 Dietary advice 595 Oral hypogl ycemic agents 595 Insulin 599 105 Diabetic eye disease 604 Epidemiology 604 Clinical features and histological features 605 Eye screening 607 Treatmen t 609 Surgical treatment 610 106 Diabetic renal disease 612 Background 612 De \201 nition 612 Epidemiology 613 Making the diagnosis 613 Pathology 614 Pathogenesis 614 Natural history 615 Treatment 616 107 Diabetic neuropathy 619 De \201 nition 619 Pathology 619 Pathogenesis 620 Peripheral sensorimotor neuropathy 621 A utonomic neuropathy 624 108 Macrovascular disease 627 Epidemiology 627 Pathogenesis 628 Draznin_Prelims.indd xxv 4/2/2011 6:51:24 PM xxvi DETAILED CONTENTS Lipid abnormalities found in patients with diabetes 629 Hypertension 632 109 Diabetic foot 636 Risk factors for foot ulcer development 637 Treatment 638 110 Diabetes and pregnancy 641 Background 641 Risks 641 Known diabetics and pregnancy 642 Gestational diabetes 644 111 Intercurrent events or disease 648 Surgery 648 Skin, connective tissue, or joint disease 649 112 Emergencies in diabetes 651 Diabetic ketoacidosis 651 Hyperosmolar, nonketotic hyperglycemia 655 Hypoglycemia 656 Part 12 Lipids and hyperlipidemia 113 Lipids and coronary heart disease 660 Physiology 660 Pathogenesis 661 Atherosclerosis 662 CHD/atherosclerosis risk factors 662 As sessment of CHD risk 663 114 Primary hyperlipidemias 669 Background 669 Polygenic hypercholesterolemia 669 Familial hypercholesterolemia (FH) 669 Cl inical characterization 670 Familial defective apolipoprotein B-100 (FDB) 671 Familial hype rtrigyceridemia 671 Rare genetic hypertriglyceridemias 671 Familial combined hyperlipidemia (FCHL) 672 Familial dysbetalipoproteinemia 672 Rare familial mixed dyslpidemias 673 115 Secondary hyperlipidemias 674 Background 674 Causes 674 Draznin_Prelims.indd xxvi 4/2/2011 6:51:24 PM DETAILED CONTENTS xxvii 116 Management of dyslipidemia 677 Background 677 Primary and secondary prevention 677 Drug therapy 678 Aims of treatment 684 Part 13 Laboratory endocrinology 117 Pitfalls in laboratory endocrinology 688 Introduction 688 Pre-analytical factors 689 Analytical factors 690 Post-analytical factors 691 118 Reference intervals 693 Introduction 693 Thyroid function 693 Adrenal and gonadal function 694 Pituitary hormones 6 95 Bone biochemistry 696 Plasma gastrointestinal and pancreatic hormones 696 Tumor markers 697 Urinary collections 697 Draznin_Prelims.indd xxvii 4/2/2011 6:51:24 PM xxviii Symbols and abbreviations i d l 4 5 5-FU ACE ACTH AD ADA ADH ADHH AF AGE AHA AIH AIT AITD ALP ALT AMH ANCA ANP APE AP ECED increased/ing decreased/ing no change/normal male female 5- \202 uorouracil angiotensin-co nverting enzyme adrenocorticotropic hormone autosomal dominant American Diabetes Associatio n antidiuretic hormone autosomal dominant hypocalcemic hypercalciuria atrial \201 brillat ion advanced glycation end-products American Heart Association amiodarone-induced hypothyro idism amiodarone-induced thyrotoxicosis autoimmune thyroid disease alkaline phosphatase ala nine transaminase anti-M llerian hormone antineutrophil cytoplasmic antibody atrial natriu retic peptide autoimmune polyglandular syndrome autoimmune polyendocrinopthy, candidiasis a nd epidermal dystrophy autoimmune polyglandular syndrome assisted reproductive techniques a spartate transaminase American Thyroid Association antithyroid drug Adult Treatment Panel a rginine vasopressin bis die (twice a day) bone mineral density body mass index B-type natri uretic peptide APS ART AST ATA ATD ATP AVP bid BMD BMI BNP Draznin_Prelims.indd xxviii 4/2/2011 6:51:24 PM DETAILED CONTENTS xxix SYMBOLS AND ABBREVIATIONS BP CaE CAH CBC CBG CD CHF CHD CK CKD CMV CNS CPA CPK CRF CRH CSF CSII CST CSW CT CTLA-4 CVD CVP DA DCCT DDAVP DEX DHEA DHEAS DHT DI DIDMOAD blood pressure calcium excretion congenital adrenal hyperplasia complete blood count cortis ol-binding globulin Cushing \200\231s disease congestive heart failure coronary heart disea se creatinine kinase chronic kidney disease cytomegalovirus central nervous system cyproter one acetate creatine phosphokinase chronic renal failure corticotropin-releasing hormone ce rebrospinal \202 uid continuous subcutaneous insulin infusion cortrosyn stimulating test cerebral salt wasting syndrome computed tomography cytotoxic T-lymphocyte antigen 4 cardiov ascular disease central venous pressure dopamine agonist Diabetes Control and Complications Trial desamino-D-arginine vasopressin dexamethasone dihydroepiandrosterone DHEA sulfate di hydrotestosterone diabetes insipidus d iabetes i nsipidus, DM , o ptic a trophy + sensorine ural d eafness (Wolfram \200\231s syndrome) deciliter diabetes mellitus deoxycortisterone d isorders of sex development dexamethasone suppression test differentiated thyroid carcinoma deep vein thrombosis dL DM DOC DSD DST DTC DVT Draznin_Prelims.indd xxix 4/2/2011 6:51:24 PM xxx SYMBOLS AND ABBREVIATIONS DETAILED CONTENTS DXA EBRT ED EE2 ENT ESR ESRF ESS ETDRS FAI FBC FCHL FDB FDG FFM FH FHH FIHP FMTC FNAC FSH F T 4 FTC g GAD GC GCT GFR GH GHBH GHD GHRH GI GIFT GIP GLP-1 GNRH GRA GRTH h HAART dual energy X-ray absorptiometry external beam radiation therapy erectile dysfunction ethin ylestradiol ear, nose, throat erythrocyte sedimentation rate end-stage renal failure empty sella syndrome Early Treatment of Diabetic Retinopathy Study free androgen index full blood count familial combined hyperlipidemia familial defective apolipoprotein B-100 [18F] \202 uorodeoxyglucose fat free mass familial hypercholesterolemia familial hypocalciuric hyperc alcemia familial isolated hyperparathyroidism familial medullary thyroid carcinoma \201 n e needle aspiration cytology follicle stimulating hormone free T 4 follicular thyroid carci noma gram(s) glutamic acid decarboxylase glucocorticoids germ cell tumor glomerular \201 ltation rate growth hormone growth hormone \200\223binding hormone growth hormone de \201 ciency growth hormone \200\223releasing hormone gastrointestinal gamete intrafallopian tran sfer gastric inhibitory peptide glucogen-like polypeptide 1 gonadotropin-releasing hormone glucocorticoid remedial aldosteronism generalized resistance to thyroid hormone hour(s) hig hly active antiretroviral therapy Draznin_Prelims.indd xxx 4/2/2011 6:51:24 PM DETAILED CONTENTS xxxi SYMBOLS AND ABBREVIATIONS HC hCG HDL HERS 5HIAA HLA hMG HMG CoA HNF HP HPA HPT-JP HPV HRT HSG HZV ICSI ID IDDM IDL IF G IGF-1 IGFPT IGT IHD IHH IM IPSS IRMA ITT IU IUD IUGR IUI IV IVF KS L LCAT LCCSCT LDL hydrocortisone human chorionic gonadotrophin high-density lipoprotein Heart and Estrogen-Pr ogestin Replacement Study 5-hydroxyindole acetic acid human leukocyte antigen human menopau sal gonadotropin 3-hydroxy-3-methylglutaryl coenzyme A hepatic nuclear factor hypothalamus \200\223pituitary hypothalmic \200\223pituitary \200\223adrenal (axis) hyperparathyroidism \200\223jaw tumor syndrome human papillomavirus hormone replacement therapy hysterosalpingo graphy herpes zoster virus intracytoplasmic sperm injection intradermal insulin-dependent d iabetes mellitus (type 1) intermediate-density lipoprotein impaired fasting hyperglycemia i nsulin-like growth factor 1 insulin-like growth factor binding protein impaired glucose tol erance ischemic heart disease idiopathic hypogonadotrophic hypogonadism intramuscular infer ior petrosal sinus sampling intraretinal microvascular abnormalities insulin tolerance test international units intrauterine device intrauterine growth retardation intrauterine insem ination intravenous in vitro fertilization Kaposi sarcoma liter(s) lecithin:cholesterol acy ltransferase large-cell calcifying Sertoli cell tumor low-density lipoprotein Draznin_Prelims.indd xxxi 4/2/2011 6:51:24 PM SYMBOLS AND ABBREVIATIONS DETAILED CONTENTS xxxii LFT LH LHRH MC mcg MEN MHC MI MIBG MIS mL MODY MPH MRI MRSA MTC NASH NF NFA NG NGF NICE NIC H NIDDM NOF NSAID NVD NVE OCP od OGTT 25OHD 17OHP OHSS PAI PCOS PCT PDE PET PHP liver function test luteinizing hormone luteinizing hormone \200\223releasing hormone miner alocorticoid microgram(s) multiple endocrine neoplasia major histocompatibility complex myo cardial infarct 123 iodine-metaiodobenzylguanidine M llerian inhibitory substance millilit er(s) maturity-onset diabetes of the young mid-parental height magnetic resonance imaging m ethicillin-resistant Staphylococcus aureus medullary thyroid cancer nonalcoholic steatohepa titis neuro \201 bromatosis nonfunctioning pituitary adenoma nasogastric nerve growth fact or National Institute for Health and Clinical Excellence non \200\223islet cell hypoglycemi a non \200\223insulin-dependent diabetes mellitus (type 2) National Osteoporosis Foundation nonsteroidal anti-in \202 ammatory drug new vessels on the disc (diabetic retinopathy) ne w vessels elsewhere (diabetic retinopathy) oral contraceptive pill omni die (once a day) or al glucose tolerance test 25-hydroxy vitamin D 17-hydroxyprogesterone ovarian hyperstimulat ion syndrome platelet activator inhibitor polycystic ovary syndrome postcoital test phospho diesterase positron emission spectrography primary hyperparathyroidism Draznin_Prelims.indd xxxii 4/2/2011 6:51:24 PM DETAILED CONTENTS xxxiii SYMBOLS AND ABBREVIATIONS PI PID PIH PMC PNMT PO POEMS protease inhibitor pelvic in \202 ammatory disease pregnancy-induced hypertension papillar y microcarcinoma of the thyroid phenylethanolamine- N -methyl transferase per os (by mouth) progressive polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes premature ovarian failure premature ovary insuf \201 ciency pro-opiomelanocortin p rogesterone-only pill pancreatic polypeptide plasma renin activity postprandial reactive hy poglycemia proton pump inhibitor prolactin pituitary resistance to thyroid hormones prostat ic-speci \201 c antigen papillary thyroid carcinoma parathyroid hormone parathyroid hormon e \200\223related peptide propylthiouracil every (q2h: every 2 hours) quality of life radio active iodine therapy renal cysts and diabetes Rathke \200\231s cleft cyst radiofrequency a blation recombinant human GH reverse T 3 thyroid hormone resistance subcutaneous subcutaneo us insulin infusion standard deviation selective estrogen replacement modulator small for g estational age sex hormone binding globulin systemic lupus erythematosus single-fraction ra diosurgery POF POI POMC POP PP PRA PRH PPI PRL PRTH PSA PTC PTH PTHrP PTU q QoL RAI RCAD RCC RFA rhGH rT 3 RTH SC SCII SD SERM SGA SHBG SLE SRS Draznin_Prelims.indd xxxiii 4/2/2011 6:51:25 PM SYMBOLS AND ABBREVIATIONS DETAILED CONTENTS xxxiv SSRI T t T 3 T 4 TB TBG TBI TBPA TC TCA TFT Tg TG TGF tid TNF TPO TPP TR TRH TSAb TSH TS H-RAB TSS TTR U&Es UFC UKPDS US VEGF VHL VIP VLDL VMA WBS WHI WHO XRT ZE