(Greenspan’s basic clinical endocrinology) david g gardner, dolores m shoback greenspan’s basic and clinical endocrinology mcgraw hill education medical (2017)

a LANGE medical book Greenspan’s Basic & Clinical Endocrinology Tenth Edition Edited by David G Gardner, MD, MS Mount Zion Health Fund Distinguished Professor of   Endocrinology and Medicine Chief, Division of Endocrinology and Metabolism Department of Medicine and Diabetes Center University of California, San Francisco Dolores Shoback, MD Professor of Medicine Department of Medicine University of California, San Francisco Staff Physician, Endocrine-Metabolism Section,   Department of Medicine San Francisco Veterans Affairs Medical Center New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto 00-Gardner_FM-pi-xxiv.indd 09/06/17 4:03 PM Copyright © 2018 by McGraw-Hill Education All rights reserved Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher ISBN: 978-1-25-958929-4 MHID: 1-25-958929-3 The material in this eBook also appears in the print version of this title: ISBN: 978-1-25-958928-7, MHID: 1-25-958928-5 eBook conversion by codeMantra Version 1.0 All trademarks are trademarks of their respective owners Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark Where such designations appear in this book, they have been printed with initial caps McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs To contact a representative, please visit the Contact Us page at www.mhprofessional.com Notice Medicine is an ever-changing science As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required The authors and 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ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE McGraw-Hill Education and its licensors not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom McGraw-Hill Education has no responsibility for the content of any information accessed through the work Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise Francis Sorrel Greenspan, M.D (1920-2016) The tenth edition of Greenspan’s Basic & Clinical Endocrinology is dedicated to the memories of four outstanding endocrinologists—Dr John Baxter, Dr Claude Arnaud, Dr Melvin Grumbach, and, most especially, Dr Francis Greenspan who was responsible for taking the initial steps to assemble this textbook more than thirty years ago Each of these individuals was an outstanding endocrine scientist and/or clinical endocrinologist in the global endocrine community, and each contributed enormously to the success of this textbook 00-Gardner_FM-pi-xxiv.indd 09/06/17 4:03 PM This page intentionally left blank 00-Gardner_FM-pi-xxiv.indd 09/06/17 4:03 PM Contents Authors Preface xix xxiii   1.  Hormones and Hormone Action Edward C Hsiao, MD, PhD and David G Gardner, MD, MS Relationship to the Nervous System  Chemical Nature of Hormones  Endocrine Glands and Target Organs  Regulation of Hormone Levels in Plasma  Hormone Biosynthesis  Precursor Processing  Hormone Release  Hormone Binding in Plasma  Hormone Metabolism  Regulation of Hormone Levels  Hormone Action  Receptors 5 Neurotransmitter and Peptide Hormone Receptors  G Protein–Coupled Receptors  G Protein Transducers  Effectors 9 Disorders of G Proteins and G Protein–Coupled Receptors 11 Growth Factor Receptors  13 Cytokine Receptors  14 Growth Hormone and Prolactin Receptors  14 TGF-b Receptors  15 TNF-Receptors 16 WNT/Beta Catenin  16 Guanylyl Cyclase–Linked Receptors  18 Nuclear Action of Peptide Hormones  19 Nuclear Receptors  19 Steroid Receptor Family  20 Thyroid Receptor Family  22 Nongenomic Effects of the Steroid Hormones  26 Steroid and Thyroid Hormone Receptor Resistance Syndromes 26  2. Endocrine Autoimmunity Juan Carlos Jaume, MD Basic Immune Components and Mechanisms  30 Immune Recognition and Response  30 Tolerance 33 T-Cell Tolerance  33 B-Cell Tolerance  35 Autoimmunity Is Multifactorial  37 Genetic Factors in Autoimmunity  37 Environmental Factors in Autoimmunity  38 Single-Gland Autoimmune Syndromes  38 Autoimmune Aspects of Thyroid Disease  38 Genes and Environment  39 00-Gardner_FM-pi-xxiv.indd Autoimmune Response  39 Animal Models of Autoimmune Thyroid Disease  40 Autoimmune Aspects of Type Diabetes  40 Genes and Environment  40 Autoimmune Response  41 Animal Models of Autoimmune Diabetes Mellitus  42 Autoimmune Aspects of Other Endocrinopathies  42 Autoimmune Adrenal Failure  42 Autoimmune Oophoritis and Orchitis  43 Autoimmune Hypophysitis  43 Autoimmune Hypoparathyroidism  43 Autoimmune Polyendocrine Syndromes  44 Autoimmune Polyendocrine Syndrome (APS-1) 44 Autoimmune Polyendocrine Syndrome (APS-2) 45 Management of Autoimmune Polyendocrine Syndromes 46 Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-Linked (IPEX) Syndrome  46 POEMS Syndrome (Osteosclerotic Myeloma)  46  3.  Evidence-Based Endocrinology and Clinical Epidemiology 49 David C Aron, MD, MS and Ajay Sood, MD 29 Clinical Epidemiology  49 Diagnostic Testing: Test Characteristics  49 Sensitivity and Specificity  50 ROC Curves  52 Predictive Values, Likelihood Ratios, and Diagnostic Accuracy 53 An Approach to Diagnosis in Practice  53 Clinical Epidemiologic Principles Applied to Treatment Decisions 56 Decision Analysis  57 Determine the Probability of Each Chance Event  59 Deciding on a Strategy: Averaging Out and Folding Back the Tree  59 Discounting Future Events  59 Sensitivity Analysis  59 Cost-Effectiveness Analysis Using Decision Analysis  59 Other Aspects of Clinical Epidemiology  60 Evidence-Based Endocrinology  60 Step One: Translation of the Clinical Problem into Answerable Questions  60 Step Two: Finding the Best Evidence  60 Step Three: Appraising the Evidence for Its Validity and Usefulness 63 Steps Four and Five: Applying the Results in Practice and Evaluating Performance  65 Developments That May Affect the EBM Approach  65 09/06/17 4:03 PM vi    CONTENTS   4.  Hypothalamus and Pituitary Gland 69 Bradley R Javorsky, MD, David C Aron, MD, MS, James W Findling, MD, and J Blake Tyrrell, MD Anatomy and Embryology  70 Blood Supply  72 Pituitary Development and Histology  72 Hypothalamic Hormones  75 Hypophysiotropic Hormones  75 Neuroendocrinology: The Hypothalamus as Part of a Larger System  78 The Hypothalamus and the Control of Appetite  79 The Pineal Gland and the Circumventricular Organs 79 Anterior Pituitary Hormones  80 Adrenocorticotropic Hormone and Related Peptides 80 Biosynthesis 80 Function 81 Measurement 81 Secretion 81 Growth Hormone  82 Biosynthesis 82 Function 82 Measurement 82 Secretion 83 Prolactin 84 Biosynthesis 84 Function 84 Measurement 85 Secretion 85 Thyrotropin 86 Biosynthesis 86 Function 86 Measurement 86 Secretion 86 Gonadotropins: Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) 87 Biosynthesis 87 Function 88 Measurement 88 Secretion 88 Endocrinologic Evaluation of the HypothalamicPituitary Axis  89 Evaluation of Adrenocorticotropic Hormone  89 Plasma ACTH Levels  89 Evaluation of ACTH Deficiency  89 Adrenal Stimulation  89 Pituitary Stimulation  89 ACTH Hypersecretion  91 Evaluation of Growth Hormone  91 Insulin-Induced Hypoglycemia  92 GHRH-Arginine Test  92 Glucagon Stimulation Test  92 Tests with Levodopa, Arginine, and Other Stimuli  92 GH Hypersecretion  92 Evaluation of Prolactin  92 Evaluation of Thyroid-Stimulating Hormone  92 Basal Measurements  92 TRH Test  92 00-Gardner_FM-pi-xxiv.indd Evaluation of LH and FSH 92 Testosterone and Estrogen Levels  92 LH and FSH Levels  92 GnRH Test  92 Problems in Evaluation of the HypothalamicPituitary Axis  92 Obesity 93 Diabetes Mellitus  93 Uremia 93 Starvation and Anorexia Nervosa  93 Depression 93 Pharmacologic Agents and Alcohol  93 Endocrine Tests of Hypothalamic-Pituitary Function 93 Neuroradiologic Evaluation  93 Magnetic Resonance Imaging (MRI)  94 Pituitary and Hypothalamic Disorders  95 Etiology and Early Manifestations  95 Common and Later Manifestations  95 Empty Sella Syndrome  96 Etiology and Incidence  96 Clinical Features  96 Diagnosis 96 Hypothalamic Dysfunction  97 Clinical Features  97 Diagnosis 97 Treatment 97 Hypopituitarism 98 Etiology 98 Clinical Features  100 Diagnosis 102 Treatment 103 Pituitary Adenomas  104 Treatment 105 Posttreatment Follow-Up  105 Prolactinomas 106 Pathology 106 Clinical Features  106 Differential Diagnosis  107 Diagnosis 107 Treatment 108 Selection of Therapy for Prolactinomas  109 Acromegaly and Gigantism  109 Pathology 110 Etiology and Pathogenesis  110 Pathophysiology 110 Clinical Features  110 Diagnosis 112 Differential Diagnosis  113 Treatment 113 Response to Treatment  114 Posttreatment Follow-Up  114 ACTH-Secreting Pituitary Adenomas: Cushing Disease  114 Pathology 114 Pathogenesis 114 Clinical Features  115 Diagnosis 115 Treatment 115 Nelson Syndrome  116 09/06/17 4:03 PM CONTENTS     vii Pathogenesis 116 Incidence 116 Clinical Features  117 Diagnosis 117 Treatment 117 Thyrotropin-Secreting Adenomas  117 Gonadotropin-Secreting Pituitary Adenomas  117 Alpha Subunit-Secreting Pituitary Adenomas  117 Nonfunctional Pituitary Adenomas  117 Pituitary Carcinoma  118   5. The Posterior Pituitary (Neurohypophysis) 121 Alan G Robinson, MD Physiology of Hormone Function  121 Anatomy of Hormone Synthesis and Release  123 Pathophysiology 123 Deficient Vasopressin: Diabetes Insipidus  124 Diagnostic Tests of Diabetes Insipidus  127 Treatment of Diabetes Insipidus  128 Excess Vasopressin: Syndrome of Inappropriate Antidiuretic Hormone 128 Treatment of Hyponatremia in SIADH 131 Summary 132 Oxytocin 132  6. Growth 137 Dennis Styne, MD Normal Growth  137 Intrauterine Growth  137 The Placenta  138 Classic Hormones of Growth and Fetal Growth  138 Growth Factors and Oncogenes in Fetal Growth  138 Insulin-Like Growth Factors, Receptors, and Binding Proteins 138 Insulin 139 Epidermal Growth Factor  139 Fibroblast Growth Factor  139 Genetic, Maternal, and Uterine Factors  139 Chromosomal Abnormalities and Malformation Syndromes 140 Fetal Origins of Adult Disease  140 Postnatal Growth  140 Endocrine Factors  141 Other Factors  144 Catch-up Growth  146 Measurement of Growth  146 Height 147 Relation to Midparental Height: The Target Height  147 Technique of Measurement  148 Height and Growth Rate Summary  148 Weight and BMI  148 Skeletal (Bone) Age  150 Disorders of Growth  150 Short Stature due to Nonendocrine Causes  150 Turner Syndrome and Its Variants  152 Noonan Syndrome (Pseudo-Turner Syndrome)  152 Prader-Willi Syndrome  152 Bardet-Biedl Syndrome  152 00-Gardner_FM-pi-xxiv.indd Autosomal Chromosome Disorders and Syndromes 152 Skeletal Dysplasias  152 Short Stature due to Endocrine Disorders  154 Congenital Growth Hormone Deficiency  154 Acquired Growth Hormone Deficiency  155 Other Types of GH Dysfunction  156 Diagnosis of GH Deficiency  156 Treatment of GH Deficiency  157 Diagnosis of Short Stature  165 Evaluation of Short Stature  165 Tall Stature due to Nonendocrine Causes  167 Cerebral Gigantism  167 Marfan Syndrome  167 Homocystinuria 167 Beckwith-Wiedemann Syndrome  167 XYY Syndrome  167 Klinefelter Syndrome  167 Tall Stature due to Endocrine Disorders  167   7.  The Thyroid Gland 171 David S Cooper, MD and Paul W Ladenson, MD (Oxon)., MD Embryology, Anatomy, and Histology  171 Physiology 172 Structure and Synthesis of Thyroid Hormones  172 Iodine Metabolism  172 Thyroid Hormone Synthesis and Secretion  174 Thyroglobulin 174 Iodide Transport  175 Thyroid Peroxidase  176 Iodination of Thyroglobulin  176 Coupling of Iodotyrosyl Residues in Thyroglobulin  176 Proteolysis of Thyroglobulin and Thyroid Hormone Secretion 176 Intrathyroidal Deiodination  177 Abnormalities in Thyroid Hormone Synthesis and Release 177 Dietary Iodine Deficiency and Inherited Defects  177 Effects of Iodine Excess on Hormone Biosynthesis  178 Thyroid Hormone Transport  178 Thyroxine-Binding Globulin  178 Transthyretin (Thyroxine-Binding Prealbumin)  179 Albumin 179 Metabolism of Thyroid Hormones  180 Control of Thyroid Function and Hormone Action  181 Thyrotropin-Releasing Hormone  182 Thyrotropin (Thyroid-Stimulating Hormone)  182 Effects of TSH on the Thyroid Cell  183 Serum TSH  184 Control of Pituitary TSH Secretion  185 Other Thyroid Stimulators and Inhibitors  185 The Actions of Thyroid Hormones  185 Effects on Fetal Development  187 Effects on Oxygen Consumption, Heat Production, and Free Radical Formation  187 Cardiovascular Effects  187 Sympathetic Effects  187 Pulmonary Effects  188 Hematopoietic Effects  188 09/06/17 4:03 PM viii    CONTENTS Gastrointestinal Effects  188 Skeletal Effects  189 Neuromuscular Effects  189 Effects on Lipid and Carbohydrate Metabolism  189 Endocrine Effects  189 Physiologic Changes in Thyroid Function  189 Thyroid Function in the Fetus  189 Thyroid Function in Pregnancy  189 Changes in Thyroid Function with Aging  190 Effects of Acute and Chronic Illness on Thyroid Function (Euthyroid Sick Syndrome)  190 Thyroid Autoimmunity  191 Tests of Thyroid Function  191 Tests of Thyroid Hormones in Blood  192 Serum TSH Measurement  192 Serum T4 and T3 Measurements  194 Assessment of Thyroid Iodine Metabolism and Biosynthetic Activity 195 Thyroid Imaging  195 Thyroid Ultrasonography and Other Imaging Techniques 196 Thyroid Biopsy  197 Test of Peripheral Thyroid Hormone Actions  198 Measurement of Thyroid Autoantibodies  198 Disorders of the Thyroid  199 History 199 Physical Examination  199 Hypothyroidism 200 Etiology and Incidence  200 Pathogenesis 201 Clinical Presentations and Findings  201 Diagnosis 203 Complications 204 Treatment 205 Adverse Effects of T4 Therapy  206 Course and Prognosis  206 Hyperthyroidism and Thyrotoxicosis  206 Etiology 207 Pathogenesis 207 Clinical Features  208 Other Presentations  210 Complications 211 Treatment of Graves Disease  211 Choice of Therapy  213 Treatment of Complications  213 Course and Prognosis  214 Toxic Adenoma  215 Toxic Multinodular Goiter (Plummer Disease)  215 Amiodarone-Induced Thyrotoxicosis  215 Subacute and Silent Thyroiditis  216 Thyrotoxicosis Factitia  216 Rare Forms of Thyrotoxicosis  216 Resistance to Thyroid Hormone Syndromes 217 TSH Receptor Gene Mutations  217 Nontoxic Goiter  217 Etiology 217 Pathogenesis 218 Clinical Features  218 Differential Diagnosis  218 00-Gardner_FM-pi-xxiv.indd Treatment 219 Course and Prognosis  220 Thyroiditis 220 Clinical Features  220 Differential Diagnosis  220 Treatment 221 Course and Prognosis  221 Etiology and Pathogenesis  221 Clinical Features  221 Differential Diagnosis  222 Complications and Sequelae  222 Treatment 222 Course and Prognosis  222 Effects of Ionizing Radiation on the Thyroid Gland  223 Thyroid Nodules and Thyroid Cancer  223 Etiology 224 Differentiation of Benign and Malignant Lesions  224 Management of Thyroid Nodules  227 Pathology 229 Management of Thyroid Cancer  231   8.  Metabolic Bone Disease 239 Dolores M Shoback, MD, Anne L Schafer, MD, and Daniel D Bikle, MD, PhD Cellular and Extracellular Calcium Metabolism  239 Parathyroid Hormone  240 Anatomy and Embryology of the Parathyroid Glands 240 Secretion of Parathyroid Hormone  241 Synthesis and Processing of Parathyroid Hormone  242 Clearance and Metabolism of PTH  243 Assays of PTH  243 Biologic Effects of PTH  244 Mechanism of Action of Parathyroid Hormone  244 PTHrP 245 Calcitonin 245 Vitamin D  246 Nomenclature 246 Cutaneous Synthesis of Vitamin D  248 Dietary Sources and Intestinal Absorption  248 Binding Proteins for Vitamin D Metabolites  248 Metabolism 249 Mechanisms of Action  251 How Vitamin D and PTH Control Mineral Homeostasis  253 Medullary Carcinoma of the Thyroid  254 Hypercalcemia 256 Clinical Features  256 Mechanisms 256 Differential Diagnosis  257 Disorders Causing Hypercalcemia  258 Etiology and Pathogenesis  258 Clinical Features  259 Treatment 260 Variants of Primary Hyperparathyroidism  263 Thyrotoxicosis 264 Adrenal Insufficiency  264 Hypervitaminosis D  265 Hypervitaminosis A  265 Immobilization 265 Acute Renal Failure  265 09/06/17 4:03 PM CONTENTS     ix Treatment of Hypercalcemia  266 Hypocalcemia 266 Classification 266 Clinical Features  266 Causes of Hypocalcemia  267 Surgical Hypoparathyroidism  267 Idiopathic Hypoparathyroidism  268 Familial Hypoparathyroidism  268 Other Causes of Hypoparathyroidism  268 Clinical Features  269 Pathophysiology 269 Genetics 270 Diagnosis 270 Pathogenesis 270 Clinical Features  271 Treatment 271 Treatment of Hypocalcemia  272 Acute Hypocalcemia  272 Chronic Hypocalcemia  272 Bone Anatomy and Remodeling  272 Functions of Bone  272 Structure of Bone  273 Bone Mineral  274 Bone Cells  274 Bone Modeling and Remodeling  275 Osteoporosis 276 Gain, Maintenance, and Loss of Bone  277 Bone Loss Associated with Estrogen Deficiency  278 Bone Loss in Later Life  279 Diagnosis of Osteoporosis  279 Management of Osteoporosis  280 Nonpharmacologic Aspects of Osteoporosis Management 280 Pharmacologic Approaches to Osteoporosis Management 281 Antiresorptive Agents  282 Bone-Forming Agents  283 Glucocorticoid-Induced Osteoporosis  283 Pathophysiology 284 Prevention and Treatment of Glucocorticoid-Related Osteoporosis 284 Pharmacologic Therapy of Glucocorticoid-Related Osteoporosis 285 Osteomalacia and Rickets  285 Pathogenesis 285 Diagnosis 285 Clinical Features  285 Treatment 287 Nephrotic Syndrome  287 Hepatic Osteodystrophy  288 Drug-Induced Osteomalacia  288 Hypophosphatemic Disorders  288 X-Linked and Autosomal Dominant Hypophosphatemia 288 Tumor-Induced Osteomalacia  289 Fibrous Dysplasia  289 De Toni-Debré-Fanconi Syndrome and Hereditary Hypophosphatemic Rickets with Hypercalciuria  289 Calcium Deficiency  290 Primary Disorders of the Bone Matrix  290 Osteogenesis Imperfecta  290 00-Gardner_FM-pi-xxiv.indd Hypophosphatasia 290 Fibrogenesis Imperfecta Ossium  290 Inhibitors of Mineralization  291 Aluminum 291 Fluoride 291 Paget Disease of Bone (Osteitis Deformans)  291 Etiology 291 Pathology 291 Pathogenesis 291 Genetic Forms  291 Clinical Features  292 Complications 292 Treatment 293 Bone Disease in Chronic Kidney Disease  294 Pathogenesis 294 Clinical Features  295 Treatment 295 Hereditary Forms of Hyperphosphatemia  295 Tumoral Calcinosis  295   9. Glucocorticoids and Adrenal Androgens 299 Ty B Carroll, MD, David C Aron, MD, MS, James W Findling, MD, and J Blake Tyrrell, MD Embryology and Anatomy  300 Embryology 300 Anatomy 300 Microscopic Anatomy  300 Biosynthesis of Cortisol and Adrenal Androgens  301 Steroidogenesis 301 Regulation of Secretion  304 Circulation of Cortisol and Adrenal Androgens  306 Plasma-Binding Proteins  306 Free and Bound Cortisol  306 Metabolism of Cortisol and Adrenal Androgens  306 Conversion and Excretion of Cortisol  306 Conversion and Excretion of Adrenal Androgens 308 Biologic Effects of Adrenal Steroids  308 Glucocorticoids 308 Molecular Mechanisms  308 Glucocorticoid Agonists and Antagonists  308 Intermediary Metabolism  311 Effects on Other Tissues and Functions  311 Adrenal Androgens  313 Effects in Males  313 Effects in Females  313 Laboratory Evaluation  313 Plasma ACTH  314 Plasma Cortisol  314 Salivary Cortisol  314 Plasma Free Cortisol  315 Urinary Corticosteroids  315 Dexamethasone Suppression Tests  315 Pituitary-Adrenal Reserve  316 Androgens 317 Disorders of Adrenocortical Insufficiency  317 Primary Adrenocortical Insufficiency (Addison Disease)  317 Etiology and Pathology  317 Pathophysiology 320 09/06/17 4:03 PM 902    Index Osteosclerotic myeloma, 46-47 Outflow tract disorders, 476 Ovarian adrenal rest tumors, 530 Ovarian amenorrhea, 463-466, 464f Ovarian differentiation, 506-507 b-catenin pathway in, 508 DAX1, 508-509 “default pathway theory” of, 508 description of, 506-507 DMRT1, 508-509 follicular morphogenesis, 508 FOXL2 as marker of, 508 genetic theories about, 508 germ cells in, 509 pathways in, 507-509 RSPO pathway in, 508 WNT pathway in, 508 Ovarian failure diagnosis of, 464 primary, hypergonadotropic hypogonadism and, 562 Ovarian function disorders, in AIDS patients, 815-816 Ovarian hormones description of, 446-447 of pregnancy, 577, 578f-579f Ovary aging of, 476, 477f anatomy of, 444-445 differentiation of, 506-507 embryology of, 444-445 follicular development in, 451f, 452 germ cells for stabilization of, 506 hormones secreted by, 446-447 in menstrual cycle, 450f-452f, 450-456 polycystic, 468 steroidogenesis of, 446f, 446-447, 447t-448t suspensory ligament of, 445 Ovotesticular disorders of sex differentiation, 515, 520-521, 535, 541, 544 Ovulation induction of, in hypothalamicpituitary dysfunction, 103 progestin effects on, 487-488, 489f during puberty, 554 timing of, 575 Ovulatory disorders, infertility and, 483-485 Oxygen consumption, thyroid hormone effects on, 187 Oxyphil adenomas, 224 Oxyphil cell, 241 Gardner_Index_p869-920.indd 902 Oxyphil cell carcinoma, 229 Oxytocin actions of, 132-134 in lactation, 132-134 during parturition, 134, 586 synthesis of, 123 Oxytocinase, 134 P p42 mitogen-activated protein kinases, 13 p44 mitogen-activated protein kinases, 13 P450 oxidoreductase deficiency, 524, 532 PAC-PRA ratio, 348 Paget disease of bone, 291-294, 292f-293f, 293t causes of, 291 clinical features of, 292 complications of, 292-293, 293t described, 291 genetic forms of, 291-292 imaging studies in, 292, 292f-293f laboratory findings in, 292 osteoarthritis in, 293 pathogenesis of, 291 pathology of, 291 sarcoma in, 293 symptoms and signs of, 292 treatment of, 293-294 vertebral, 293 Painful diabetic neuropathy, 666 Painless thyroiditis, 222 Pallister-Hall syndrome, 519 Pamidronate, 266 Pancreas anatomy of, 596-597, 597f, 597t, 842 described, 596 embryology of, 842 endocrine See Endocrine pancreas histology of, 596-597, 597f, 597t hormones of, 597-608 See also specific hormone ghrelin, 608 glucagon, 605-607, 606f, 607t insulin, 597-605, 598f-602f, 601t, 603t pancreatic polypeptide, 608 somatostatin, 607f, 607-608 maternal, during pregnancy, 581, 583 transplantation of, in insulin administration, 645 Pancreatic b cells autosomal dominant, 615-618, 617t destruction of, in NOD mouse model, 41 genetic defects of, 618-619 tumors of, 690-695, 692t, 692f Pancreatic cholera, 754 Pancreatic neuroendocrine tumors, 694 Pancreatic peptides, in food intake regulation, 733, 733t Pancreatic polypeptides, 608, 861t Pancreatic surgery complications, 845 Pancreatic tumors, nonfunctioning, 844-845 Pancreatitis, 711 Papaverine hydrochloride, 436 Papillary carcinoma management of, 231-235, 233f of thyroid gland, 228f, 229 Papillitis, necrotizing, 664 Parafollicular cells, 171, 174f, 230 Paraganglia, 359-412 See also Paraganglioma Paraganglioma, 373-409 cardiac, 386 defined, 360 described, 373 genetic conditions associated with, 375t-376t, 375-382 Beckwith-Wiedemann syndrome, 382 Carney triad, 382 MEN 2, 375t, 376 NF-1, 376, 376t, 381 von Hippel-Lindau disease, 376t, 376-378 germline mutations in, 376, 380-382 glomus jugulare, 365, 374 incidence of, 373 jugulotympanic, 374 management of, 397-402 manifestations of, 384-388, 385t medical management of, 397-400 metastatic, 374, 403-408, 404t, 408f nonchromaffin parasympathetic, 374 normotension despite high plasma levels of norepinephrine with, 388 pathology of, 403 pathophysiology of, 383f peptide secretion by, 383t, 383-384 physiology of, 382 prevalence of, 373-375 prognosis of, 408-409 screening for, 375, 375t somatic mutations in, 382 07/06/17 2:20 PM Index     903 tricarboxylic acid cycle mutations as cause of, 378-379 in von Hippel-Lindau disease, 376 Paralysis, periodic, thyrotoxic See Thyrotoxic periodic paralysis Parasympathetic preganglionic nerves, 359-360 Parathyroid disease, during pregnancy, 591 Parathyroid gland anatomy of, 240-241, 832 embryology of, 240-241, 832 maternal, during pregnancy, 581, 582f-583f surgery of complications of, 838 for hyperparathyroidism familial, 837 primary, 832, 834-836, 836t secondary, 837 Parathyroid hormone (PTH), 240-246, 241f-246f assays of, 243-244 biologic effects of, 244 clearance and metabolism of, 243 hypermagnesemia effects on, 241 immunoradiometric assay for, clinical utility of, 257f mechanism of action of, 244-245 in mineral homeostasis control, 253-272 normal ranges for, 862t osteoporosis fracture prevention with, 283 PTHrP, 245, 745-746 secretion of, 241f, 241-242 synthesis and processing of, 242, 244f Parathyroid hormone (PTH)–related protein, 862t Parathyroidectomy bilateral versus unilateral approach to, 836 conduct of, 836 rationale and guidelines for, 835, 836t subtotal versus total, with autotransplantation, 836 Paricalcitol, 247t, 295 Parinaud syndrome, 80 Paroxysmal hyperthermia, 97 Paroxysms, pheochromocytomas and, 384-385 Partial ACTH deficiency assessment, in adrenocortical insufficiency diagnosis, 324 Partial androgen insensitivity syndrome, 525, 537, 543 Gardner_Index_p869-920.indd 903 Partial gonadal dysgenesis, 522 Parturition See also Labor and delivery endocrine control of, 585-586 oxytocin during, 134 Parvicellular neurons, 79 Pasireotide, 113, 116 Pathologic short stature, 147 Pathologic uterine distention, during preterm birth, 586, 587f Patient education, in diabetes mellitus management, 646-647 P450c17 deficiency, 524 PCSK9 variants, 721 Peau d’orange, 209 Pediatric Endocrine Society, 147 Pegvisomant, 114 Pelvic disorders infertility and, 484 management of, 485 Pemberton sign, 218, 218f Pen injector devices, in insulin administration, 644 pendrin gene, 176 Penile ablation, 773 Penis agenesis of, 773 development of, 549, 551f Pentamidine, 812 Peptic ulcer, 313 Peptide(s) ACTH-related, 80f, 80-81 See also Adrenocorticotropic hormone (ACTH) angiotensin, 344f gastrointestinal, in food intake regulation, 733, 733t glucagon-related, 606-607, 607t of insulin, 849t pancreatic, in food intake regulation, 733, 733t secretion of, pheochromocytomas and paragangliomas in, 383t, 383-384 vasoactive intestinal, 868t Peptide hormone receptors, 6-7, 7f, 7t Peptide hormones, 19 Periodic paralysis, thyrotoxic, 211, 786-787, 787f, 787t Peripheral B-cell tolerance, 36f, 37 Peripheral glucose metabolism, glucocorticoid effects on, 309t, 311 Peripheral neuropathy in diabetic patients, 660t, 666 isolated, 666 Peripheral vascular disease, in diabetic patients, 660t, 668 Peripheral vasospasm, pheochromocytomas and, 386 Peripubertal gonadotropin increase, 552-553 Peristalsis, intestinal, 203 Peritubular cells, 508 Permanent neonatal diabetes (PMDM), 621 Peroxisome proliferator–activated receptor agonists, for type diabetes, 637-638 Persistence of hyperparathyroidism, 761 Persistent hyperinsulinism, 698t, 698-700 Persistent hyperprolactinemia, prolactinomas and, 462-463 Persistent Müllerian duct syndrome, 525, 526f Personalized medicine, 65 Pertussis toxin, G proteins and, 12 Phenoxybenzamine pheochromocytoma/paraganglioma managed with, 398, 402 in pregnancy, 402 Phentermine, for obesity, 649, 739t Phentolamine, 367 erectile dysfunction treated with, 436 growth hormone secretion affected by, 84 pheochromocytoma/paraganglioma managed with, 400-401 τ-Phenylalanine derivative, in type diabetes management, 636 Phenylethanolamine-N-methyltransferase, 361 Phenytoin, 93 Pheochromoblasts, 360 Pheochromocytoma, 338, 373-409, 840 adrenal percutaneous fine-needle aspiration biopsy for, 397 adrenalectomy for, 840 anatomy of, 360, 360f blood supply to, 361 gross structure, 360 microscopic structure, 361 nerve supply to, 361 biochemical testing for, 388-392 catecholamines, 390, 392t chromogranin A, 391 described, 388-389 dopamine, 390, 392t metanephrines, 389-391, 392t 07/06/17 2:20 PM 904    Index Pheochromocytoma, biochemical testing for (Cont.): misleading, factors causing, 391-392, 392t plasma renin activity, 391 suppression and stimulation testing, 391 vanillylmandelic acid, 391 black, 374 catecholamines in, 365-366 See also Catecholamine(s) characteristics of, 840 in children, 387 defined, 360 definition of, 373 described, 360, 373, 840 diagnosis of, 397, 840 differential diagnosis of, 392-393, 393t embryology of, 360, 360f genetic conditions associated with, 375t-376t, 375-382 Beckwith-Wiedemann syndrome, 382 Carney triad, 382 MEN 2, 375t, 376 NF-1, 376, 376t, 381 von Hippel-Lindau disease, 376t, 376-378 germline mutations in, 376, 380-382 incidence of, 373 incidentally discovered, 397 localization studies for, 393-397 computed tomography, 393-395, 394f magnetic resonance imaging, 394-395 MIBG scanning, 395f, 395t, 395-396 positron emission tomography, 396, 396f somatostatin receptor imaging with 111-In-octreotide, 397 ultrasound, 397 venous sampling for catecholamines, 383f malignant, 387 management of, 397-402 activities to avoid in, 400 anesthesia in, 401 foods to avoid in, 400 medical, 397-400 resection in, therapy for shock occurring after, 402 surgical, 400-402, 840 manifestations of, 384-388, 385t Gardner_Index_p869-920.indd 904 in MEN 2, 764, 768t metastatic, 403-408, 404t, 408f bisphosphonates in, 406-407 growth rate assessment of, 405 management of, 405-408, 408f arterial embolization in, 407 chemotherapy in, 406 131-I-MIBG therapy in, 407-408, 408f radiation therapy in, 407 RF ablation in, 407 sites of, 404, 404t surveillance of, 405 non–head-neck, 374, 374f normotension despite high plasma levels of norepinephrine with, 388 pathology of, 403 pathophysiology of, 383f peptide secretion by, 383t, 383-384 physiology of, 382 postoperative long-term surveillance of, 409 during pregnancy, 387, 402-403 prevalence of, 373-375 prognosis of, 408-409 screening for, 375, 375t somatic mutations in, 382 tricarboxylic acid cycle mutations as cause of, 378-379 unsuspected, death in patients with, 373, 373t in women, 387 PHEX gene, 754 Phosphate deficiency of, 288 diabetic ketoacidosis managed with, 656, 792 homeostasis of, in AIDS patients, 811t, 814 Phosphatidylinositol 4,5-bisphosphate, 241 Phosphatonin, 289 Phosphodiesterase inhibitor, 436 Phospholipase A2, 10 Phospholipase D, 10 Physical activity See also Exercise in glucocorticoid-induced osteoporosis prevention and treatment, 284-285 in obesity management, 739 Phytosterolemia, 722 Pineal gland, 79f, 79-80 Pioglitazone, for type diabetes, 633t, 637-638 Pit1, 72, 74f Pituitary adenomas, 104-118 See also specific adenoma acromegaly, 109-114, 111t, 112f ACTH-secreting, 109-115 clinical features of, 115 described, 114 diagnosis of, 115 pathogenesis of, 114-115 pathology of, 114 treatment of, 115-116 medical, 116 radiotherapy in, 115-116 surgical, 115 alpha subunit–secreting, 117 in Cushing disease, 328 described, 104t, 104-105 diagnosis of, 462 gigantism, 109-114, 111t gonadotropin-secreting, 117 in MEN 1, 758 Nelson syndrome, 116-117 nonfunctional, 117-118 pregnancy effects on, 590 prolactinomas, 106-109 thyrotropin-secreting, 117 treatment of, 105-106, 108-109 follow-up care, 105-106 medical, 105 radiotherapy in, 105 surgical, 105 types of, 104-118 Pituitary amenorrhea anatomic causes of, 463 endocrine causes of, 462-463 genetic causes of, 461 Pituitary apoplexy clinical setting of, 789 diagnosis of, 789 management of, 789-790 pituitary infarction secondary to, 98 Pituitary carcinoma, 118 Pituitary disorders in AIDS patients, 816 causes of, 95-96 manifestations of, 95-96 during pregnancy, 589-590 Pituitary gigantism, 167-168 Pituitary gland, 69-119 aging effects on, 479-480 anatomy of, 70-72, 71f-72f anterior, in Cushing disease, 328 blood supply to, 71f-73f, 72 congenital absence of, 155 development of, 72-75, 74f, 75t 07/06/17 2:20 PM Index     905 embryology of, 70-72, 71f-72f function of, 816 histology of, 72-75, 74f, 75t maternal, during pregnancy, 581 in menstrual cycle, 449-450 pathophysiology of, 123-124 posterior, 121-135 size of, 71 venous drainage of, 72, 73f Pituitary hormones adenohypophysial, 75t anterior, 80-81, 80f-81f fetal, 584 in puerperium, 588 Pituitary hypersecretion, 95 Pituitary insufficiency, 95 Pituitary stimulation, in ACTH evaluation, 89, 91 Pituitary-adrenal reserve, in adrenal androgen evaluation, 316-317 Placenta, 138 Placental aromatase deficiency, 531-532, 535, 544 Placental bed, 576f Placental growth factor, 592 Plasma adrenocorticotropic levels, in adrenocortical insufficiency diagnosis, 323f, 324 hormone binding in, in hormone level regulation in plasma, 4, 5f regulation of hormone levels in, 4-5, 5f Plasma free cortisol, in adrenal androgen evaluation, 315 Plasma free metanephrine, 389-390 Plasma lipoproteins abnormal patterns of, clinical differentiation of, 710-711 in lipid transport, 706, 706t, 707f Plasma osmolality, 122f, 128-129 Plasma renin activity in mineralocorticoid deficiency, 529 in pheochromocytoma testing, 391 Plasma steroids in women, 447, 448t Plasma-binding proteins androgens and, 306 cortisol and, 306 Plasma-fractionated free metanephrines, in pheochromocytoma testing, 389-390, 392t Plasminogen activator inhibitor-1 (PAI-1), 615 Platelet-derived growth factor (PDGF), 143 Gardner_Index_p869-920.indd 905 PLC beta (PLCb), 9-10, 10f Plicamycin, 797 Plummer disease, 215, 215f POEMS syndrome, 46-47, 622 Poikilothermia, 97 Polycystic ovarian syndrome (PCOS), 466t, 466-472, 468f-470f, 471t biochemical abnormalities associated with, 471 characteristics of, 467 diagnosis of, 466t, 467 hyperandrogenism and, 467-468, 468f-469f hyperinsulinemia and, 470f, 470-472, 471t management of, 472 obesity-related infertility associated with, 738 pathogenesis of adrenal gland in, 470 intraovarian modulators in, 470, 470f premature adrenarche in, 570 prevalence of, 466 risks associated with, 471 Polydipsia, primary, 124, 127 Polyendocrine syndromes, autoimmune, 44-46 APS-I, 44t, 44-45 APS-II, 44t, 45 management of, 46 Polyglandular failure syndrome, 203 Polyhydramnios, diabetes during pregnancy effects on, 673-674 Polyneuropathy, distal symmetric, 665-666 Polypeptide hormones benign and malignant tumors, 744t, 745 chorionic, 580 human placental lactogen, 577, 579f, 580 during pregnancy, 577, 578f-579f, 580 Polypeptides, pancreatic, 608, 861t Polyuria in Cushing syndrome, 332t, 333 in diabetes insipidus, 803 Positive feedback, 88 Positivity in disease (PiD), 50 Positron emission tomography (PET), of pheochromocytoma, 396, 396f Postabsorptive state, euglycemia in, 686-687, 687t Postcoital contraception, 497 Posterior pituitary, 121-135 Postnatal growth, 140-146 See also Growth, postnatal Postpartum thyroiditis, 222 Postprandial hypoglycemia, 695-696 Postprandial syndrome, 697 Postterm pregnancy, 587-588 Posttest probability, 55, 55f Posttherapy scan, 233 Potassium, for diabetic ketoacidosis, 656 Potassium-aldosterone feedback loop, 344f Prader-Willi syndrome, 150t, 152 delayed puberty and, 560 obesity caused by, 735t Pramlintide, for type diabetes, 634t, 641 Prazosin, 398 Prealbumin, thyroxine-binding, in thyroid hormone transport, 179 Precocious adrenarche, 573 Precocious puberty, 566t, 567f, 571t central, 566-568, 567f CNS disorders, 567-568 constitutional or familial, 566-567 idiopathic, 567, 567f treatment of, 572 virilizing syndrome, 568 classification of, 566, 566t described, 566 differential diagnosis of, 570-572, 571t follicular cysts and, 569 growth hormone deficiency and, 550 hypothyroidism and, 569 incomplete, 566, 572-573 isosexual in girls, 569 incomplete, in boys, 568 McCune-Albright syndrome and, 569 tall stature related to, 168 treatment of, 572-573 variations in, 569-570 Precocious thelarche, 573 Precocity contrasexual, 566 incomplete contrasexual in boys, 568 in girls, 569 isosexual, 566 sexual See Puberty, precocious Preconception counseling, for pregnant women with preexisting diabetes, 675 Predictive analytics, 65 07/06/17 2:20 PM 906    Index Predictive values, 53, 54f Prednisone, 213 Preeclampsia clinical features of, 592 described, 591-592 pathophysiology of, 592 risk factors for, 591 symptoms and signs of, 591-592 Preferred reporting items for systematic reviews and meta-analyses (PRISMA), 63 Preganglionic nerves parasympathetic, 359-360 sympathetic, 360 Pregnancy aldosterone levels in, 583 androgen exposure during, 532 conception in, 575-577, 576f corticotropin-releasing hormone in, 585-586 dexamethasone therapy in, 531 in diabetic patients, 673-680, 674t, 676t-678t See also Diabetes mellitus, pregnancy in patients with eclampsia in, 591-592 ectopic, 496 endocrine changes associated with, 575 endocrine disorders during, 589-591 endocrine function tests in, 581, 583t endocrinology of, 575-593 estrogens during, 579f, 580-581 fertilization in, 575-576 fetal-placental-decidual unit in, 577 growth factors during, 580 hyperparathyroidism in, 591 hypertension effects of, 356 hyperthyroidism in, 589 hypoparathyroidism in, 591 hypothyroidism in, 589 implantation in, 576f, 576-577 maternal adaptation to, 581-583, 582f-583f, 583t adrenal cortex, 583 pancreas, 581, 583 parathyroid gland, 581, 582f-583f pituitary gland, 581 thyroid gland, 581, 582f-583f maternal obesity effects on, 591 maternal serum hormone changes during, 578f-579f maternal virilization during, 535 obesity effects on, 590-591 ovarian hormones of, 577, 578f-579f Gardner_Index_p869-920.indd 906 parathyroid disease and, 591 pheochromocytomas during, 387, 402-403 pituitary adenomas affected by, 590 pituitary disorders in, 589-590 polypeptide hormones during, 577, 578f-579f, 580 See also Polypeptide hormones, during pregnancy postterm, 587-588 preeclampsia in, 591-592 primary aldosteronism in, 354 progesterone during, 580 spironolactone in, 354 steroid hormones during, 580-581 symptoms and signs of, 577 thyroid function in, 189-190 thyrotoxicosis during, treatment of, 214 vasopressin increase during, diabetes insipidus caused by, 126 Pregnanetriol, 862t Pregnenolone, 510, 862t Premature adrenarche, 570 Premature menarche, 570 Premature ovarian failure (POF) autoimmune origin of, 465 defined, 464 genetic origin of, 464f, 464-465 iatrogenic causes of, 465 resistant ovary syndrome and, 465-466 Premature thelarche, 569-570 Prematurity, 150t, 151 Preproinsulin, 597, 598f Preproparathyroid hormone, 242, 242f Pre-T cells, 30 Preterm birth (PTB) decidual hemorrhage and coagulation during, 586, 587f described, 586, 587f fetal stress during, 586, 587f maternal stress during, 586, 587f mechanistic pathways leading to, 586, 587f pathologic uterine distention during, 586, 587f Preterm labor, 587 Preterm rupture of membrane, 586 Pretest probability, 55, 55f Pretibial myxedema, 199-200, 208f Primary adrenal tumors, 327-328 Primary aldosteronism, 346-354 clinical presentation of, 347 described, 346t, 346-347 diagnosis of, 347-353, 348f-352f adrenal computed tomography, 350, 350f-351f adrenal venous sampling, 350-352, 352f case-detection tests, 347-348, 348f confirmatory tests, 348-349 familial hyperaldosteronism type assessment in, 353 glucocorticoid-remediable aldosteronism–familial hyperaldosteronism type assessment in, 353 intravenous saline infusion test, 349 oral sodium loading test, 349 subtype studies, 349-353, 350f-352f in pregnancy, 354 prevalence of, 347 treatment of, 353-354 Primary cortisol resistance, 355 Primary follicles, 452 Primary hyperaldosteronism, 838 Primary hyperparathyroidism (PHP), 258-264, 260f-261f, 832, 834-836, 835f, 836t, 837f causes of, 258-259 clinical features of, 259-260, 260f-261f described, 258 diagnostic tests for, 834-835, 835f hypercalcemia caused by, 258-264, 260f-261f laboratory findings in, 260 nonspecific features of, 260 normocalcemic, 836-837 pathogenesis of, 258-259 persistent, 837, 837f prevalence of, 832 recurrent, 837, 837f symptoms and signs of, 257f, 259-260, 260f-261f, 834 treatment of description of, 260, 262-263 surgical, 835-836, 836t variants of, 263-264 Primary macroadenomas, 104 Primary microadenomas, 104 Primary pigmented nodular adrenocortical disease, 329 Primary polydipsia, 124, 127 Primordial follicles, 444, 450 Primordial germ cells, 506 Progeria, 722 Progestasert, 496 Progesterone aging effects on, 479, 479t 07/06/17 2:20 PM Index     907 chemical structure of, 488f in hypothalamic-pituitary dysfunction, 103 normal ranges for, 863t during pregnancy, 580 Progesterone receptors, 585 Progestin-only pills, contraceptive, 490-491, 491f Progestins injectable, in contraception, 492f, 492-493, 493t ovulation effects of, 487-488, 489f steroidogenesis effects of, 487, 489f ProGnRH, 78 Proinsulin, 597, 598f, 599, 863t Prolactin biosynthesis of, 84 deficiency of, hypopituitarism and, 100 evaluation of description of, 92 in hypopituitarism diagnosis, 103 function of, 84-85 hypersecretion of, 106 measurements of, 85 indications for, 106, 106t in testicular function evaluation, 421, 421t normal ranges for, 863t in puerperium, 588 secretion of, 85f dopamine agonists’ effect on, 109 episodic, 85-86 estrogen effects on, 86 factors affecting, 85-86, 86t sleep-associated changes in, 85f Prolactin receptors, 14-15 Prolactinomas clinical features of, 106-107 diagnosis of, 107-108 differential diagnosis of, 107 estrogen deficiency in, 106 pathology of, 106 persistent hyperprolactinemia caused by, 462-463 treatment of dopamine agonists in, 108-109 radiotherapy in, 109 selection of, 108-109 surgical, 109 Prolactin-releasing factors, 77, 85 Proliferative retinopathy, 662, 663f Pro-opiomelanocortin (POMC), 71, 535 Prop1, 72, 74f Propranolol, 213 Gardner_Index_p869-920.indd 907 Proprotein convertase subtilisin/ketin type (PCSK9) loss of function mutations, 721 monoclonal antibody, 727 variants, 718 Propylthiouracil (PTU) chemical structure of, 177f Graves disease treated with, 211-212 in pregnancy, 214 Prostaglandins E1, 436 during parturition, 586 Protease inhibitors description of, 320 glucose and lipid metabolism effects of, 820t Protein(s) binding, for vitamin D metabolites, 248-249 CREB-binding, 9, 25 glucose transporter, insulin and, 601f, 604-605 growth hormone binding, 854t parathyroid hormone–related, 862t plasma-binding, 306 Protein tyrosine phosphatase nonreceptor type 11, 152 Proteinuria, in diabetes mellitus evaluation, 624-625 Proteolysis of thyroglobulin secretion, 175f, 176-177, 177f of thyroid hormone secretion, 175f, 176-177, 177f Proton stereotactic radiotherapy, for pituitary adenoma, 105 Protooncogenes See RET protooncogene Pseudoacromegaly, 614 Pseudoautosomal region 1, 507, 507f Pseudo-Cushing syndrome, 334-335 Pseudofractures, 287 Pseudohermaphroditism, 513 Pseudohypoaldosteronism type 1, 27 Pseudohypoparathyroidism clinical features of, 269f, 269-270 described, 269 diagnosis of, 270 genetics of, 270 hypocalcemia caused by, 269f, 269-270, 270t pathophysiology of, 269-270, 270t short stature associated with, 164 type 1, 12 Pseudoshock, pheochromocytomas and, 386 Pseudo-Turner syndrome description of, 150t, 152 hypergonadotropic hypogonadism and, 563 Pseudovitamin D deficiency, 271 Psychologic disturbances, in Cushing syndrome, 332t, 333 Psychologic factors, in postnatal growth, 146 Psychologic management, of GH deficiency, 162 Psychosocial dwarfism, 162, 163f PTH gene, 242 PTTG1 gene, 104 Puberty, 547-574 absent, 554 adrenarche during, 554, 555t bone accretion in, 551 delayed, 554-556 classification of, 556t constitutional delay in, 554, 556 defined, 554 differential diagnosis of, 563t, 563-564 hypergonadotropic hypogonadism in, 560-563 See also Hypogonadism, hypergonadotropic hypogonadotropic hypogonadism in, 556-560 See also Hypogonadism, hypogonadotropic in Klinefelter syndrome, 426, 522 radiation therapy and, 558 treatment of, 564-566 bone mass–related, 566 coexisting GH deficiency–related, 565 constitutional delay–related, 564-565 permanent hypogonadism– related, 565 described, 547 development during, variations in, 569-570 endocrine changes in, 550-554 GnRH stimulation, 553 sex steroid secretion, 553 growth hormone deficiency and, 156 leptin and, 553-554 menarche in, 554 metabolic changes during, 554 ovulation in, 554 07/06/17 2:20 PM 908    Index Puberty (Cont.): physical changes associated with, 547-551, 548f-549f age at onset of, 549-550 body composition–related, 550-551, 551f in females, 548-549, 548f-549f growth spurt, 550 in males, 549, 551f physiology of, 547-554 precocious, 566t, 567f, 571t central, 566-568, 567f CNS disorders, 567-568 constitutional or familial, 566-567 idiopathic, 567, 567f treatment of, 572 virilizing syndrome, 568 classification of, 566, 566t described, 566 differential diagnosis of, 570-572, 571t follicular cysts and, 569 growth hormone deficiency and, 550 hypothyroidism and, 569 incomplete, 566, 572-573 isosexual in girls, 569 incomplete, in boys, 568 McCune-Albright syndrome and, 569 tall stature related to, 168 treatment of, 572-573 variations in, 569-570 suppression of, in transgender youth, 774-776, 776t Pubic hair development in females, 548f-549f, 549 in males, 549, 551f PubMed, 60 Puerperium, 588 Pulmonary system hypothyroidism effects on, 203 obesity effects on, 737 pheochromocytoma effects on, 387 thyroid hormone effects on, 188 Pure gonadal dysgenesis, 519, 543 Pyogenic infections of skin, 668 PYY, 733 Q Quality-adjusted life years (QALYs), 59-60 R Rabson–Mendenhall syndrome, 620 Rachitic rosary, 285 Radiation, ionizing, 223 See also Radiotherapy Gardner_Index_p869-920.indd 908 Radioactive iodine for Graves disease, 212 thyroid uptake of (RAIU), 866t Radiofrequency (RF) ablation, for pheochromocytoma/ paraganglioma, 407 Radiographic dyes in diabetic patients, 664-665 Radioimmunoassay (RIA), 193, 195 Radionuclide imaging, of thyroid gland, 195-196, 196f Radiosurgery, gamma knife, 105 Radiotherapy acromegaly managed with, 114 ACTH-secreting pituitary adenoma managed with, 115-116 delayed puberty related to, 558 pheochromocytoma/paraganglioma managed with, 407 pituitary adenoma managed with, 105 prolactinoma managed with, 109 protein stereotactic, for pituitary adenoma, 105 Raloxifene, 282, 481 Raltegravir, 820t Randomized controlled trials (RCTs), 63 RANKL description of, 252 inhibition of, in osteoporosis management, 283 Rapid ACTH stimulation test in adrenocortical insufficiency diagnosis, 322-323, 323f in hypothalamic-pituitary function evaluation, 90t Ras–Raf complex, 13 Rathke cleft cysts, 97 Rathke pouch, 71, 556 Ratio cortisol-corrected, 352, 352f likelihood, in clinical epidemiology, 53, 55f RCCX, 527 Receiver-operating characteristic (ROC) curves, 52-53, 54f 5α-Reductase type deficiency, 524-525 Regulatory T cells, 35 Relative adrenal insufficiency, 320 Relative risk reduction (RRR), 56 Remodeling process, 276 Renal artery stenosis, 392 Renal calculi, in Cushing syndrome, 332t, 333 Renal cell carcinoma, hypercalcemia of malignancy and, 746 Renal failure, acute, 265 Renal function, hypothyroidism effects on, 203 Renal osteodystrophy, 294f, 294-295 Renal parenchymal disease, 392 Renal system, diabetes effects on, 660t, 663-665 Renal tubular acidosis, 153 Renal tubular ionic transport, abnormal, 356 Renin, 343-344, 344f, 864t Renin-angiotensin system, 344f Renin-angiotensin-aldosterone feedback loop, 344f Renin-angiotensin-aldosterone system, 343-346, 344t, 344f-345f aldosterone, 345f, 345-346 angiotensin, 343-345, 344f angiotensin II, 344-345 angiotensinogen, 344, 344f Repaglinide, for type diabetes, 633t, 636 Reproducibility, 50 Reproductive system female anatomy of, 444-445, 444f-445f embryology of, 444-445, 444f-445f endocrinology of, 444-499 hypothyroidism effects on, 203 male, 415-418, 416f, 417t, 419f gonadal steroids in, 415-417, 416f-417f, 417t testicular function in, 417f, 417-418 obesity effects on, 738 Resistant ovary syndrome, 465-466 RET mutations clinical presentations resulting from, 254, 254t frequency of, 254, 255t RET protooncogene in MEN 2, 376, 376t in MEN 2A, 765 in paraganglioma, 380 in pheochromocytoma, 380 Rete testis, 415 Retinaldehyde dehydrogenases, 509 Retinoic acid, 509 Retinoic acid receptors, 251 Retinoic X receptors, 251 Retinol-binding protein (RBP), 265 Retinopathy diabetic, 660t, 662-663 during pregnancy, 675 nonproliferative, 660t, 662, 662f proliferative, 660t, 662, 663f 07/06/17 2:20 PM Index     909 Reverse T3 (RT3), 195, 868t Rickets clinical features of, 285-287, 286f defined, 285 hypophosphatemic autosomal dominant, 288-289 hereditary, with hypercalciuria, 289-290 imaging studies in, 287 laboratory findings in, 286-287 pathogenesis of, 285, 286t symptoms and signs of, 285-286, 286f treatment of, 287 vitamin D–resistant, hereditary, 271-272 Riedel thyroiditis, 223 Rifampin, 812 Rilpivirine, 820t Ritonavir, 820t Robinow syndrome, 519 Rokitansky-Küster-Hauser syndrome, 563 Rosiglitazone, for type diabetes, 633t, 637-638 Roux-en-Y gastric bypass (RYGB) dumping syndrome after, 696 in obesity management, 740 postprandial hypoglycemia after, 696, 696t type diabetes mellitus managed with, 649 R-Spondin 1, 508, 521 Rubenstein-Taybi syndrome, 27 Ruffled border, 274, 275f S Saccharin, 632 Salivary cortisol, 314, 334 Sandwich assays, 193, 553 Saquinavir, 820t Sarcoidosis hypercalcemia caused by, 264 hypopituitarism and, 98-99 Sarcoma, 293 Satiation, 733 Satiety, 733 Satiety center, 78 Saxagliptin, for type diabetes, 633t, 640 Scatchard equation, 6, 6f Schmidt syndrome, 205, 221 Sclerostin, 16 SDHB gene mutations, 379 SDHC gene mutations, 379 SDHD gene mutations, 379 Gardner_Index_p869-920.indd 909 Secondary follicles, 452 Secondary hyperparathyroidism, 837 Seip-Berardinelli syndrome, 721 Seizures, 267 Selective estrogen receptor modulators (SERMs), for osteoporosis, 282, 481 Self-management training, for diabetes mellitus, 646-647 Sella turcica definition of, 71 enlarged, pituitary disorders and, 95 Sellar masses, parasellar masses versus, 104t Semen analysis, in testicular function evaluation, 421 Semen washing, 814-815 Seminiferous tubules anatomy of, 414f, 415 description of, 413 dysgenesis of, hypergonadotropic hypogonadism and, 560-561 formation of, 508 Seminomas, 439 Sensitivity, 50-51, 52t, 52f-53f Sensitivity analysis, 59 SERKAL syndrome, 521 Serpentine receptors, 6-7, 7f, 7t Sertoli cell only syndrome, 561 Sertoli cells, 413, 415, 505, 551 Serum fructosamine levels, in diabetes mellitus evaluation, 628 ketone levels, in diabetes mellitus evaluation, 626-627 T4 and T3 measurements in, 194-195, 195t thyroxine levels, in euthyroid individuals, 179t SETD2 gene, 382 “Seven-transmembrane-domain” receptors, 6-7, 7f, 7t 72-hour fast, in insulinoma diagnosis, 691, 692t Sex, 514, 771 Sex assignment description of, 539 for ovotesticular disorders of sex differentiation, 541 principles of, 539 specific considerations for, 540-541 for 46,XX DSD patients with genital ambiguity, 540 for 46,XY DSD patients with genital ambiguity, 540 Sex chromosome(s) aneuploidies, gonadal dysgenesis in, 522 in gonadal differentiation, 507f historical views on, 515 Sex chromosome disorders of sex differentiation definition of, 563 fertility issues for, 544 Sex hormone–binding globulin (SHBG), 111, 415, 553, 583, 864t Sex steroids for delayed puberty, 564-565 excess of described, 839-840 diagnostic tests for, 840 surgical management of, 840 during parturition, 586 in postnatal growth, 144 secretion of, during puberty, 553 for transgender adults continuing use of, 780 protocols for, 777t, 778 Sexual development disorders of See Disorders of sex differentiation (DSDs) secondary, normal, primary amenorrhea associated with, 563 Sexual identity, 514, 772 Sexual orientation, 514 Sexual precocity, 566t, 567f, 571t See also Precocious puberty Shock, 385-386, 402 Short chain L-3-hydroxyacyl-CoA dehydrogenase, 699 Short stature chronic disease associated with, 150t, 153 constitutional, 150t, 151 diagnosis of, 165t, 165-166 endocrine disorders and, 150t, 154-164 Cushing syndrome, 163-164 diabetes insipidus, 165 diabetes mellitus, 165 hypothyroidism, 162-163 pseudohypoparathyroidism, 164 psychosocial dwarfism, 162, 163f vitamin D metabolism disorders, 165 evaluation of, 165t, 165-166 familial, 150t, 151 malnutrition and, 150t, 153 medications effects on, 150t, 154 07/06/17 2:20 PM 910    Index Short stature (Cont.): nonendocrine causes of, 150t, 150-154 pathologic, 147 syndromes of, 150t, 151-152 autosomal chromosomal disorders/ syndromes, 150t, 152 Bardet-Biedl syndrome, 150t, 152, 560, 735t growth hormone deficiency, 150t, 154f, 154-162, 158t, 159f-161f Laurence-Moon syndrome, 150t, 151 Noonan syndrome, 150t, 152 Prader-Willi syndrome, 150t, 152 pseudo-Turner syndrome, 150t, 152 skeletal dysplasia, 150t, 152 Turner syndrome, 150t, 152 Shunts, cortisol-cortisone, 307f, 307-308 Sick euthyroid syndrome, 210 Signaling, insulin See Insulin signaling Silent thyroiditis, 210, 216, 222 Sipple syndrome, 380-381 Sitagliptin, for type diabetes, 633t, 639-640 Skeletal age, 150 Skeletal dysplasias, 150t, 152 Skeleton/skeletal system glucocorticoid effects on, 284 thyroid hormone effects on, 189 Skin chronic pyogenic infections of, in diabetic patients, 668 Cushing syndrome effects on, 332, 332t diabetes effects on, 660t, 668-669 hypocalcemia effects on, 267 Skin spots, in diabetic patients, 669 SLC34A3, 289 Sleep growth hormone secretion during, 85f prolactin secretion during, 85-86 Small nuclear riboprotein polypeptide N, 152 Small-for-gestational age (SGA) prematurity and, 150t, 151 transient hyperinsulinism in, 698, 698t Smith-Lemli-Opitz syndrome, 523 Smoking, atherosclerosis caused by, 706 Smooth muscle, extravascular, 371 Socioeconomic factors, in postnatal growth, 146 Sodium bicarbonate, for diabetic ketoacidosis, 656 Gardner_Index_p869-920.indd 910 Sodium-iodide symporter, 173 Soluble fms-like tyrosine kinase 1, 592 Somatomedin, 142 Somatostatin, 76, 78f, 607f, 607-608 characteristics of, 75-76 in GH secretion, 83 normal ranges for, 864t in thyrotropin secretion, 87 Somatostatin analogs, for congenital hyperinsulinism, 701 Somatostatin receptor imaging, 396-397 Somatostatinoma, 844 Somatotrophs, 73, 75t SOX3, 508, 521 SOX8, 508 SOX9, 504, 507-508, 521 SOX10, 508, 521 Spasm, carpal, 266, 267f Specificity, 50-51, 52t, 52f-53f Spermatogenesis in hypothalamic-pituitary dysfunction, 104 male infertility–related defects of, 434 Spermaturia, 549 Sphingolipidoses, 722 Spinal stenosis, 293 Spironolactone, 346, 353-354, 573 Squamous cell carcinoma, hypercalcemia of malignancy and, 746 SRD5A2 gene, 511 SRY gene, 507, 507f Starvation, 93 Stature See Short stature; Tall stature Stavudine, 820t Steatohepatitis, nonalcoholic, 715-716 Steno-2 study, 630-631 Steroid(s) adrenal, 308, 309t-310t, 311-313 See also Glucocorticoid(s) adrenocortical, 302f adrenocortical insufficiency managed with, 326, 326t gonadal, 415-417, 416f-417f, 417t plasma, in women, 447, 448t in puerperium, 588 sex See Sex steroids testicular function evaluations using measurements of, 421, 421t Steroid hormone(s) nongenomic effects of, 26 during pregnancy, 580-581 Steroid hormone receptor resistance syndromes, 26-27 Steroid receptor complex, signaling through, 20, 20f Steroid receptor molecule, 21f Steroid receptors, 20f-21f, 20-22, 22t Steroidogenesis, 301-304, 302f, 303t adrenal, disorders of, 526-531 adrenocorticotropic hormone and, 304-305, 305f androgen synthesis in, 304 cholesterol in metabolism of, 304 uptake and synthesis of, 303-304 corticotropin-releasing hormone secretion in, 304 cortisol synthesis in, 302f, 304 definition of, 510 in fetal sex differentiation, 510-511 intraovarian factors in, 453 ovarian, 446f, 446-447, 447t-448t progestin effects on, 487, 489f zones and, 302, 302f Steroidogenic acute regulatory protein (StAR), 446, 510 Steroidogenic pathway, 303t Stiff person syndrome, 610-611 Stimulation tests, in hypopituitarism diagnosis, 103 Stimulus-secretion coupling, 241 STRA8, 509 Stress ACTH and cortisol secretion and, 305 fetal, during preterm birth, 586, 587f maternal, during preterm birth, 586, 587f Strontium ranelate, 283 Struma ovarii, 216 Study of Women’s Health Across the Nation, 479 Subacute thyroiditis, 216, 220f, 220-221 clinical features of, 220, 220f course of, 221 differential diagnosis of, 220-221 prognosis of, 221 treatment of, 221 Subarachnoid hemorrhage, 130 Subcapsular cataracts, 267, 660t, 663, 799 Subclinical hyperthyroidism, 210 Subclinical hypothyroidism, 203 Subdermal implants, in contraception, 494-495 Subfertility, 483 Succinate dehydrogenase gene mutations, 379-380 Sulfation factor, 142 Sulfonylurea receptors 07/06/17 2:20 PM Index     911 drugs acting on, for type diabetes, 633t hyperinsulinism and, 698-699 Sulfonylureas, for type diabetes, 633t, 634-635, 650, 688 Sunitinib, 406, 695 Suppression, active, 34f, 35 Suppressor of cytokine signaling (SOCS) proteins, 15 Suppressor T cells, 35 Suprarenal gland See Adrenal gland Surfactant protein A, 586 SWAN See Study of Women’s Health Across the Nation Sweeteners, in diabetes management, 632 Swyer syndrome, 519 Sympathetic nervous system, thyroid hormone effects on, 187-188 Sympathetic preganglionic nerves, 360 Sympathoadrenal activity regulation, catecholamine receptors in, 369-370 Syndrome of gonadal dysgenesis See Gonadal dysgenesis Syndrome of inappropriate antidiuretic hormone (SIADH) causes of, 131, 131t, 750t, 750-751 cerebral salt wasting versus, 801 clinical features of, 751 clinical syndromes of, 131, 131t described, 128-129, 129t, 750 diabetes insipidus versus, 133t hyponatremia in pathophysiology of, 129-131, 130f treatment of, 131-132 laboratory features of, 751 pathogenesis of, 750-751 pathophysiology of, 133t Syndrome of inappropriate thyroid-stimulating hormone secretion, 216-217 Syringe administration, of insulin, 644 Systematic reviews, 63 Systemic lupus erythematosus, 29 T T cell(s) activation of, 30-32, 32f antigen recognition by, 31, 32f helper, 39 pre-, 30 regulatory, 35 suppressor, 35 tolerance of, 33-35, 34f Tall stature cerebral gigantism, 167 Gardner_Index_p869-920.indd 911 constitutional, 167 endocrine disorders and, 167-168 familial, 167 nonendocrine causes of, 167 syndromes of, 167-168 Tangier disease, 719 T-cell receptor (TCR) genes, 30, 31f Temozolomide, 406 10% tumor See Pheochromocytoma Tenofovir, 820t, 822 Terazosin, 398 Teriparatide, 283, 285 Testes, 413-441 See also specific testicular disorders accessory structures, 415 anatomy of, 413, 414f, 415 blood supply to, 415 components of, 413, 415 descent of, 513 differentiation of, 505-506 fetal sex differentiation role of, 504f rete, 415 structure-function relationships of, 413, 414f, 415 Testicular adrenal rest tumors, 529-530 Testicular biopsy, 422 Testicular differentiation description of, 505-506 germ cells in, 509 pathways in, 507-509 testicular morphogens in, 508 Testicular dysgenesis syndrome, 536-537, 561 Testicular failure, primary, 561 Testicular function control of, 417f, 417-418 disorders of, in AIDS patients, 814-815 laboratory tests of, 420-422, 421t in male reproductive system, 417f, 417-418 Testicular tumors causes of, 439 clinical features of, 440 course of, 441 differential diagnosis of, 440-441 imaging studies in, 440 incidence of, 439 laboratory findings in, 440 pathology of, 439-440 prevalence of, 439 prognosis of, 441 symptoms and signs of, 440 treatment of, 441 Testis-specific enhancer, 508 Testolactone, 573 Testosterone biosynthesis defect involving, 524 implantable pellets, 424 injectable esters, 423-424 metabolites of, 510 normal ranges for, 864t-865t production of, 510 serum in luteinizing hormone and follicle-stimulating hormone evaluation, 92 measurement of, 420 in newborns, 535t side effects of, 424-425 transdermal, 424 in transgender men, 778 Testosterone cypionate, 423 Testosterone enanthate, 423 Testosterone propionate, 423 Testosterone undecanoate, 104, 423 Tetany definition of, 266 generalized, 799 hypocalcemic, carpal spasm caused by, 266, 267f Thelarche, premature, 569-570 Thiamine-responsive megaloblastic anemia syndrome, 619 Thiazide diuretics hypercalcemia caused by, 265 hypocalcemia caused by, 272 Thiazolidinediones in AIDS endocrinopathies, 818 in type diabetes management, 633t, 637-638, 650 Thiocarbamide inhibitors, of thyroidal iodide organification, 177f Thiouracil, 177f Thirst, in Cushing syndrome, 333 Thromboembolic events, nonketotic hyperosmolar coma and, 795 Thyrocytes, 172-173 Thyroglobulin coupling of iodotyrosyl residues in, in thyroid hormone synthesis, 176, 176f described, 174-175, 175f iodination of processes of, 175f, 176 in thyroid hormone synthesis, 176 normal ranges for, 866t secretion of, proteolysis of, 175f, 176-177, 177f in thyroid hormone synthesis, 174-175, 175f 07/06/17 2:20 PM 912    Index Thyroglobulin gene, 175, 175f Thyroid antibodies, 866t Thyroid autoantibodies, 198-199, 210 Thyroid cancer, 227t-228t, 229-236, 231f-233f, 235t, 828t-829t differentiated, 232 course of, 235, 235t management of, 235, 235t prognosis of, 235, 235t surgery for, 828t-829t, 828-830 lymph nodes in, 831, 831f management of, 231-236, 233f, 235t medullary, 830 metastatic, 831-832 molecular biology of, 231, 231f-232f pathology of, 228t, 229-231, 231f-232f recurrent, 831-832 staging of, 234f, 829f surgical treatment of, 828t-829t, 828-830 undifferentiated, 830-831 Thyroid carcinoma, 216 Thyroid cell function, thyroidstimulating hormone effects on, 183-184 Thyroid dermopathy, 208, 208f Thyroid diseases/disorders, 199-223 See also specific disorder in AIDS patients described, 809-810 medication effects, 810-811, 811t neoplasms, 810 opportunistic infections, 810 prevalence of, 809 thyroid function tests in, alterations in, 810, 810t in animal models, 40, 40f anovulation and, 475 autoimmune aspects of, 38-40, 40f autoimmune response, 38-40 genes and environment, 39 Graves disease, 207-214 history of, 199 hyperthyroidism, 206-217 See also Hyperthyroidism hypothyroidism See Hypothyroidism nontoxic goiter See Nontoxic goiter physical examination of, 199, 200f thyroid cancer See Thyroid cancer thyroid hormone resistance syndromes, 217 thyroid nodules See Thyroid nodules thyroiditis See Thyroiditis thyrotoxicosis See Thyrotoxicosis Gardner_Index_p869-920.indd 912 Thyroid function tests in AIDS patients with thyroid disorders, 810, 810t in HIV-infected patients, 810, 810t Thyroid gland, 171-236 abnormalities of, 826 anatomy of, 171-172, 172f, 174f, 825-826 autoimmune disease of, 221f autoimmunity of, 191 biopsy of, 197-198 biosynthetic activity of, 195, 195f blood supply of, 172, 173f developmental abnormalities of, 826 disorders of See Thyroid diseases/ disorders dysfunction of, hypertension and, 357 ectopic, 201 embryology of, 171-172, 825-826 examination of, 200f biopsy, 197-198 description of, 199 imaging tests, 195-197, 196f-197f in measurement of thyroid autoantibodies, 198-199 of peripheral thyroid hormone actions, 198 fetal, 584 functions of acute and chronic illness effects on, 190f, 190t, 190-191 aging effects on, 190 control of, 181-189 in fetus, 189 glucocorticoid effects on, 309t, 313 physiologic changes in, 189-191, 190f, 190t in pregnancy, 189-190 serum TSH in, 184-185 tests of serum T4 and T3 measurements, 194-195, 195t serum TSH measurements, 192f-193f, 192-194, 194t in thyroid iodine metabolism assessment, 195, 195f thyroid stimulators, 185 thyroid-releasing hormone in, 180t, 182f thyroid-stimulating hormone in, 182-183, 183f-184f thyrotropin in, 182-183, 183f-184f thyrotropin-releasing hormone in, 182 histology of, 171-172, 174f imaging of, 195-197, 196f-197f iodine metabolism in, 172-177, 175f-177f See also Iodine, metabolism of ionizing radiation effects on, 223 maternal, during pregnancy, 581, 582f-583f medullary carcinoma of, 254t-255t, 254-256 See also Medullary carcinoma of thyroid (MCT) metastases to, 231, 831-832 parafollicular cells of, 76 physiology of, 172, 174f release of, abnormalities in, 177-178 structure of, 172, 174f surgery of indications for, 826-832, 829t, 831f cancer, 229-236, 828-830, 829t See also Thyroid cancer developmental thyroid abnormalities, 826 goiter, 827 hyperthyroidism, 826-827 thyroid nodules, 827-828 thyroiditis, 827 resections in, types of, 826t synthesis of, 172, 174f abnormalities in, 177-178 inherited defects and, 177-178 veins of, 826 Thyroid hormone(s) See also specific hormone actions of, 185-189, 186f-188f biosynthesis of, iodine excess effects on, 178 in blood, tests of, 191-199, 192f-193f, 194t-195t serum T4 and T3 measurements, 194-195, 195t serum TSH measurement, 192f-193f, 192-194, 194t control of, 181-189 metabolism of, 180t, 180-181, 180f-181f peripheral, 198 physiologic effects of, 186-189, 188f in postnatal growth, 144 resistance to, 27 secretion of description of, 174-177, 175f-177f proteolysis of, 175f, 176-177, 177f structure of, 174f synthesis of, 174-177, 175f-177f transport of, 178f-179f, 178-180, 179t albumin in, 179-180 07/06/17 2:20 PM Index     913 thyroxine-binding globulin in, 178-179, 179t transthyretin in, 179 Thyroid hormone receptor resistance syndromes, 26-27 Thyroid hormone receptors (THRs), 185-186, 186f-187f Thyroid hormone resistance syndromes, 217 Thyroid hormone-binding ratio (THBR), 192f-193f Thyroid iodine, 195, 195f Thyroid lymphoma pathology of, 231 surgery for, 831 Thyroid nodules, 223-229, 224t-225t, 226f-227f benign, 224-229 causes of, 224 clinical features in, 224 malignant lesions versus, 224-227, 225t history of, 224 imaging studies in, 226f malignant, 224-227, 225t management of description of, 227-229, 230f surgical, 827-828 needle biopsy of, 225-227 Thyroid peroxidase antibodies, 39 Thyroid peroxidase (TPO), 176 Thyroid receptors, 22-26, 23f-24f Thyroid stimulators, 185 Thyroid storm, 211, 785t, 785-786 clinical setting of, 785, 785t diagnosis of, 785 management of, 213, 785-786, 786t Thyroid transcription factor 1, 825 Thyroid transcription factor 2, 825 Thyroid uptake of radioactive iodine (RAIU), 866t Thyroidal iodide organification, thiocarbamide inhibitors of, 177f Thyroidectomy complications of, 832 conduct of, 832, 833f-834f indications for, 826-832 Thyroiditis chronic, 221f, 221-222 See also Hashimoto thyroiditis lymphocytic, 221f, 221-222 painless, 222 postpartum, 222 Riedel, 223 Gardner_Index_p869-920.indd 913 silent, 210, 216, 222 subacute, 216, 220f, 220-221 clinical features of, 220, 220f course of, 221 differential diagnosis of, 220-221 prognosis of, 221 treatment of, 221 surgery for, 827 Thyroid-releasing hormone, 86-87 Thyroid-releasing hormone test, 92 Thyroid-stimulating antibodies, 207 Thyroid-stimulating hormone receptor antibody (TSH-RAb), 866t Thyroid-stimulating hormone (TSH) in control of thyroid function, 182-183, 183f-184f deficiency of, hypopituitarism and, 100 evaluation of, 92 function of, thyroid cell effects on, 183-184 hypopituitarism and, 103 in hypothyroidism diagnosis, 163 measurement of, 192f-193f, 192-195, 194t normal ranges for, 866t secretion of pituitary, 185 syndrome of inappropriate, 216-217 serum, in control of thyroid function, 184-185 Thyroid-stimulating hormone (TSH) receptor gene mutations, 217 Thyroid-stimulating hormone (TSH)–TSH-R complex, 182-183, 184f Thyroid-stimulating hormone-receptor (TSH-R), 39 Thyrotoxic crisis, 211, 213 Thyrotoxic periodic paralysis clinical setting of, 786 description of, 211 diagnosis of, 786-787, 787f management of, 787, 787t Thyrotoxicosis, 206-217 amiodarone-induced, 215-216, 787-788, 788t clinical setting of, 787-788 management of, 787-788, 788t conditions associated with, 207, 207t definition of, 172 forms of, 215f, 215-217 gestational, 214 hamburger, 216 during pregnancy, 214 tall stature and, 168 Thyrotoxicosis factitia, 216 Thyrotrophs, 73-74, 75t Thyrotropin, 86f biosynthesis of, 86 function of, 86 measurement of, 86 secretion of, 86-87 in thyroid function control, 182-183, 183f-184f Thyrotropin-binding inhibitory immunoglobulin (TB-II), 866t Thyrotropin-releasing hormone (TRH), 77 chemical structure of, 182f location of, 78f structure of, 77t in thyroid function control, 180t, 182, 182f Thyrotropin-secreting pituitary adenomas, 117 Thyroxine (T4) free, 867t for hypothyroidism, 163 measurement of, 194-195, 195t metabolic pathways of, 180f, 180-181 normal ranges for, 867t Thyroxine-binding globulin (TBG) congenital deficiency of, 178 description of, 810 normal ranges for, 866t-867t in thyroid hormone transport, 178-179, 179t Thyroxine-binding prealbumin, in thyroid hormone transport, 179 Time trade-off method, 59 Tipranavir/ritonavir, 820t Tissue adipose, 309t, 311 connective, 310t, 311 Tissue heterogeneity, in insulin resistance in type diabetes, 614 Tolazamide, for type diabetes, 633t, 635 Tolbutamide, for type diabetes, 633t, 635 Tolerance, T-cell, 33-35, 34f Tolvaptan, 132 Topiramate, 739t Total metanephrines, 389 Toxic adenoma, 215, 215f Toxic multinodular goiter, 215, 215f Toxin cholera, 11 pertussis, 12 07/06/17 2:20 PM 914    Index Trabecular bone, 273 Transcortical bone biopsy, 287 Transcription factors description of, 72 in early development of mouse pituitary, 74f Transcriptional regulation, insulin-related, 602, 602f Transdermal patch, in contraception, 495f, 495-496 Transducers, G protein, 8t, 8-9, 9f Transforming growth factor (TGF), 450 Transforming growth factor beta (TGF-b), 276 Transforming growth factor beta (TGF-b) receptors, 15-16, 16f Transgender, 771-772 Transgender adults aging of, 780 clinical presentation of, 777-778 endocrine management of, 778-779 estradiol treatment of, 779 female-to-male hormone protocols for, 777t-778t, 778, 780 hysterectomy in, 780 feminization of, 778t hormone protocols for, 777t-778t, 778-779 long-term care of, 780 male-to-female hormone protocols, 777t-778t voice therapy for, 780 medical evaluation of, 777t men, 778 neovagina in, 779 reproductive options for, 779-780 sex steroids continuing use of, 780 protocols for, 777t, 778 surgical considerations for, 779 testosterone treatment for, 778 voice therapy for, 780 women, 779 Transgender youth areas of uncertainty for, 776 barriers to care for, 776 bone mineral density in, 774-775 clinical practice guidelines for, 774 definitions associated with, 771-772 early pubertal, 774-775 family support effects on, 772 female-to-male, 775, 775t late pubertal, 775-776, 775t-776t male-to-female, 775, 775t Gardner_Index_p869-920.indd 914 management of, 774-776, 775t-776t mental health concerns, 772 natural history of, 773-774 overview of, 771 prevalence of, 772 pubertal suppression in, 774-776, 776t research priorities for, 776 terms associated with, 771-772 World Professional Association for Transgender Health Standards of Care, 771-772 Transient neonatal diabetes (TNDM), 621 Transient receptor potential cation channel (TRPV6), 252 Transmembrane protein 127, 381 Transplantation islet cell, 645-646 pancreas, 645 Transsexualism, 773 Transsphenoidal microsurgery acromegaly treated with, 113 Cushing disease treated with, 115 macroadenomas treated with, 109 pituitary adenomas treated with, 105 Transthyretin, 179 TR–associated protein (TRAP), 25 Trauma, diabetes insipidus caused by, 125 Treatment effect heterogeneity, 65 Treatment threshold probability, 55 Tricarboxylic acid cycle mutations, 378-379 Triiodothyronine (T3) description of, 368 measurement of, 194-195, 195t normal ranges for, 867t-868t reverse, 195 Trimethoprim, 812 Triptolide, 406 Trousseau sign, 267, 799 True hermaphrodites/hermaphroditism, 464, 513 Tuberculosis, 319 Tumor(s) See also specific tumor adrenal Cushing disease caused by, 332 Cushing syndrome caused by, 328 pathophysiology of, 332 treatment of, 337 primary, 327-328 prognosis of, 337 androgen-secreting, hyperandrogenism and, 473-474 carotid body, 374 DOC-producing, 355 endocrine, hypercalcemia caused by, 264-265 germ cell, 439-441 gonadotropin-secreting, in boys, 568 hormones secreted by, 752-753 Leydig cell, testicular, 439-441 localization of, in acromegaly diagnosis, 113 neuroendocrine, pancreatic exploration for, 845 neuroendocrine cell, 745 osteomalacia caused by, 289 pancreatic b-cell, 690-695, 692t, 692f See also Insulinomas nonfunctioning, 844-845 progression of, prolactinomas and, 107 10% See Pheochromocytoma testicular See Testicular tumors testicular germ cell, 439-441 Tumor localization studies, in insulinoma diagnosis, 692f, 692-693 Tumor necrosis factor-α, 736 Tumor necrosis factor receptor-associated factors (TRAFs), 16 Tumor necrosis factor (TNF) receptors, 16, 16f Tumoral calcinosis, 295 Turner syndrome See also Gonadal dysgenesis clinical features of, 522 description of, 150t, 152 hypergonadotropic hypogonadism and, 562 infant, 562 male, 430 See also Noonan syndrome premature ovarian failure in, 464 prevalence of, 522 variants of, 522 24-hour urine-fractionated metanephrines, 390 × table, 56, 57f Tyrosine, catecholamines synthesized from, 362 Tyrosine kinase–containing growth factor receptor signaling, 13, 13f U Ulcers, peptic, 313 Ullrich syndrome, 563 Ultrasonography of pheochromocytoma, 397 of thyroid gland, 196-197, 197f Uncoupling protein 2, 700 07/06/17 2:20 PM Index     915 Undifferentiated (anaplastic) carcinoma, 230, 236 Unilateral hyperplasia, 353 United Kingdom Prospective Diabetes Study (UKPDS), 630 Universal diet, for lipoprotein disorders, 724 Urapidil, 398 Uremia pituitary function tests affected by, 93 secondary hypertriglyceridemia associated with, 715 Urine glucose levels in, in diabetes mellitus evaluation, 624 ketone levels in, in diabetes mellitus evaluation, 626-627 vanillylmandelic acid levels in, in pheochromocytoma testing, 391 Urine free cortisol, in Cushing syndrome diagnosis, 334 Urogenital ridges, 503 Urogenital sinus bipotential, 512f, 512-513 defective morphogenesis of, 516, 518f development of, 512f, 512-513 U.S Preventive Services Task Force (USPSTF), 63-64, 64t USP8 gene, 115 Uterus anatomy of, 445, 445f components of, 445, 445f distention of, during preterm birth, 586, 587f embryology of, 445, 445f fetal growth and, 139 formation of, 445, 445f location of, 445 malformation of, 516 in menstrual cycle, 456-457 size and shape of, 549 Utility measures, 58-59 V Vagina anatomy of, 445f atresia of, 516 embryology of, 445f, 513 formation of, 445f malformation of, 516 Vaginal rings, in contraception, 496 Validity of evidence, 63t-64t, 63-65 Values, predictive, 53, 54f Van Wyk-Grumbach syndrome, 569 Gardner_Index_p869-920.indd 915 Vanillylmandelic acid (VMA), 868t Vanishing testes syndrome, 429, 561 See also Anorchia, bilateral Vaptans, 132 Varicoceles, male infertility–related, 434 Vas deferens, congenital bilateral absence of, 516 Vascular diseases diabetic, classifications of, 660 peripheral, in diabetic patients, 660t, 668 Vasoactive intestinal peptide, 868t Vasomotor symptoms, menopause and, 480 Vasopressin See also Antidiuretic hormone (ADH) decreased end organ response to, 126 diabetes insipidus and, 124-126 excess, 128-132, 129t, 130f, 131t See also Syndrome of inappropriate antidiuretic hormone (SIADH) lack of See Diabetes insipidus secretion of, 121, 122f synthesis and secretion of, 123-124 Vasospasm, peripheral, 386 Verner-Morrison syndrome, 754, 844 Very low density lipoproteins (VLDL), 707, 708f Veterans Administration Diabetes Trial (VADT), 631 VHL gene description of, 138 in MEN 2, 376t, 376-378 Vildagliptin, for type diabetes, 634t, 640 VIPomas, 265, 844 Virilism, 337-338 Virilizing syndrome, central precocious puberty–related, 568 Visceral obesity, 615 Visual field defects, 96 Vitamin A, 265 Vitamin B, 724 Vitamin D, 246-253 actions of, 252-253 in bone, 252-253 in kidney, 253 analogs of, 247t cutaneous synthesis of, 248 deficiency of, 270-271 clinical features of, 271 description of, 252 laboratory findings in, 286-287 pathogenesis of, 270-271, 285, 286t rickets caused by, 285, 286t treatment of, 271, 287 dietary sources of, 248 in glucocorticoid-induced osteoporosis prevention and treatment, 284 hypercalcemia caused by, 265 intestinal absorption of, 248 in intestinal calcium transport, 251-252 mechanisms of action, 251f, 251-253 metabolism of description of, 249f-250f, 249-251 disorders of, short stature associated with, 165 metabolites of, 247t, 248-249 in mineral homeostasis control, 253-272 nomenclature associated with, 246-247, 247f, 247t-248t normal ranges for, 868t osteoporosis managed with, 281, 481 Vitamin D receptor, 251 Vitamin D receptor–interacting protein (DRIP complex), 25 Vitamin D response elements (VDREs), 251 Vitamin D–resistant rickets, hereditary, 271-272 Vitiligo, 44 Voice therapy, for transgender adults, 780 von Hippel-Lindau (VHL) disease, 376t, 376-378 multiple endocrine organ involvement in, 769 pheochromocytomas in, 377-378 von Recklinghausen disease, 769 von Recklinghausen neurofibromatosis (NF-1), 376, 376t, 381 W WAGR syndrome, 520 Weber-Christian syndrome, 722 Weight, measurement of, 148 Weight loss in obesity management, 738-740, 739t See also Obesity, weight loss for in type diabetes management, 648-649 Wermer syndrome, 757-762 See also Multiple endocrine neoplasia (MEN) Werner syndrome, 722 Whipple procedure, 845 Whole exome sequencing (WES), 539 Whole genome sequencing (WGS), 539 07/06/17 2:20 PM 916    Index Williams-Bureun syndrome of elfin facies, 164 Wilson disease, 268 Wnt4, 521 Wnt pathway, 277, 508 Wnt/b-catenin complex, 16-17, 17f Wolcott–Rallison syndrome, 619 Wolff-Chaikoff effect, 178 Wolffian ducts derivatives of, 512 description of, 445 development of, 503, 505, 509 Wolfram syndrome, 619, 803 Wolman disease, 722 Women See also Female(s) adrenal androgen effects on, 313 androgens in, in hypothalamicpituitary dysfunction, 103 luteal-follicular transition in, 448, 449f Gardner_Index_p869-920.indd 916 pheochromocytomas in, 387 plasma steroids in, 447, 448t prolactinomas and, gonadal dysfunction in, 106-107 Women’s Health Initiative (WHI), 482 World Health Organization (WHO), 731, 737 World Professional Association for Transgender Health Standards of Care, 771-772 X Xanthomatosis, cerebrotendinous, 722 X-linked hypophosphatemia (XLH), 288-289 X-linked Kallmann syndrome, 558 X-linked Opitz G/BBB syndrome, 519 XX,46 See 46,XX XXY seminiferous tubule dysgenesis, 425-427, 427f See also Klinefelter syndrome XY,46 See 46,XY XYY syndrome, 167 Y Y chromosome, 507 Yohimbine, 367 Z Zinc deficiency, 153 Zoledronic acid, 266, 282, 285, 407 Zollinger-Ellison syndrome, 843t, 843-845 Zona fasciculata, 301, 302f, 510 Zona glomerulosa, 300 Zona reticularis, 301, 302f, 510 07/06/17 2:20 PM ... Cytology 397 Medical Management of Patients with Pheochromocytoma and Paraganglioma  397 Surgical Management of Pheochromocytoma and Paraganglioma 400 Pregnancy and Pheochromocytoma/ Paraganglioma 402... Paragangliomas  375 Somatic Mutations in Pheochromocytoma and Paraganglioma 382 Physiology of Pheochromocytoma and Paraganglioma 382 Secretion of Other Peptides by Pheochromocytomas and Paragangliomas ... Management of Transgender Adults: Conclusions 780 24.  Endocrine Emergencies David G Gardner, MD, MS Myxedema Coma  783 Clinical Setting  783 Diagnosis 783 Management 784 Thyroid Storm  785 Clinical