Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text

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Through ten outstanding editions, Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text has been the go-to reference for the most comprehensive coverage of the thyroid, including anatomy, development, biochemistry, physiology, pathophysiology, and treatment of all thyroid disorders. Now in full color throughout, the 11th Edition of this award-winning text remains the clinician’s preferred source of authoritative information on the thyroid—an essential resource for all endocrinologists and thyroid surgeons. Includes thorough updates and new content throughout the text, especially on thyroid cytopathology, thyroid imaging, and targeted therapy of thyroid cancer as well as a new full-color format. Covers all aspects of the thyroid, including thyroid hormone synthesis and secretion, thyroid function, and disorders such as thyrotoxicosis, hypothyroidism, and cancer. Discusses surgical management of thyroid cancer, thyroid disruptors, thyroid hormone analogs, thyroid dysfunction’s effects on other organ systems, the aging thyroid, subclinical hypothyroidism and hyperthyroidism, and thyroid disease in pregnancy. Features insights from international experts, including new editor Dr. Peter Kopp of Northwestern University’s Feinberg School of Medicine. Enrich Your Ebook Reading Experience Read directly on your preferred device(s), such as computer, tablet, or smartphone. Easily convert to audiobook, powering your content with natural language text-to-speech. Cover Contents Section I: The Normal Thyroid A. History, Development, Anatomy Chapter 1: The heritage of the thyroid: A brief history GOITER, CRETINISM, AND THE THYROID GLAND GOITER AND IODINE THYROTOXICOSIS HYPOTHYROIDISM AND THE RECOGNITION OF THYROID FUNCTION THERAPY OF HYPOTHYROIDISM DISCOVERY OF THE ACTIVE PRINCIPLE AND THERAPY OF HYPOTHYROIDISM SCREENING AND THERAPY OF CONGENITAL HYPOTHYROIDISM DISCOVERY OF CURRENT CONCEPTS OF THYROID HORMONE SYNTHESIS, TRANSPORT, AND ACTION AUTOIMMUNE ETIOLOGY OF GRAVES DISEASE AND HASHIMOTO THYROIDITIS THYROID CANCER OUTLOOK REFERENCES Chapter 2: Development and anatomy of the hypothalamic–pituitary–thyroid axis THE HYPOTHALAMIC–PITUITARY AXIS SIGNALING AND TRANSCRIPTIONAL MECHANISMS INVOLVED IN HYPOTHALAMUS ORGANOGENESIS SIGNALING AND TRANSCRIPTIONAL MECHANISMS INVOLVED IN PITUITARY ORGANOGENESIS THE THYROID GLAND THYROID BUD FORMATION THYROID MIGRATION THYROID FOLLICULOGENESIS DIFFERENTIATED THYROID FOLLICULAR CELLS HISTOLOGY AND STRUCTURE THYROID TRANSCRIPTION FACTORS OTHER TRANSCRIPTION FACTORS INVOLVED IN THYROID DEVELOPMENT IN VITRO GENERATION OF THYROID CELLS FROM PLURIPOTENT STEM CELLS MODELING THYROID BY TRANSCRIPTION FACTORS OVEREXPRESSION MODELING THYROID BY CHEMICAL PATHWAYS MANIPULATIONS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES B. Thyroid Hormone Synthesis and Secretion Chapter 3: Thyroid hormone synthesis: Thyroid iodide transport IDENTIFICATION BY FUNCTIONAL EXPRESSION OF THE CDNA ENCODING RAT NIS THE NIS MOLECULE ISOLATION OF THE CDNA ENCODING HUMAN NIS (hNIS) AND ELUCIDATION OF THE GENOMIC ORGANIZATION OF hNIS NIS IN EXTRATHYROIDAL TISSUES NIS MECHANISM AND STOICHIOMETRY SUBSTRATE SPECIFICITY OF NIS NIS TRANSPORTS THE ENVIRONMENTAL POLLUTANT ClO4− WITH A 1 Na+:1 ClO4− STOICHIOMETRY IODIDE TRANSPORT DEFECT, A CONGENITAL CONDITION CAUSED BY MUTATIONS IN THE NIS (SLC5A5) GENE NIS KO MICE, A USEFUL MODEL FOR STUDYING MULTIPLE RAMIFICATIONS OF HYPOTHYROIDISM REGULATION OF NIS TRANSCRIPTION REGULATION OF NIS IN THE THYROID BY TSH REGULATION OF NIS BY I− REGULATION OF NIS BY A K+ CHANNEL NIS IN THYROID CANCER I− EFFLUX NIS IN BREAST CANCER IMPACT OF NIS ON PUBLIC HEALTH NIS GENE TRANSFER CONCLUDING REMARKS AND AVENUES FOR FUTURE INVESTIGATION REFERENCES Chapter 4: Thyroid hormone synthesis IODIDE UPTAKE INTO THE THYROID THE GENE AND PROTEIN STRUCTURE OF THE SODIUM/IODIDE SYMPORTER FUNCTIONAL CHARACTERIZATION OF THE SODIUM/IODIDE SYMPORTER REGULATION OF IODIDE UPTAKE AND SODIUM/IODIDE SYMPORTER FUNCTION AND EXPRESSION MUTATIONS IN THE SODIUM/IODIDE SYMPORTER GENE IODIDE EFFLUX FROM THE THYROID PENDRED SYNDROME AND PENDRIN (PDS/SLC26A4) PROTEIN STRUCTURE OF PENDRIN EXPRESSION AND REGULATION OF PENDRIN FUNCTIONAL CHARACTERIZATION OF PENDRIN GOITER AND THYROID DYSFUNCTION IN PENDRED SYNDROME ANOCTAMIN SLC26A7 THYROGLOBULIN STRUCTURE OF THE THYROGLOBULIN GENE AND PROTEIN MUTATIONS IN THE THYROGLOBULIN GENE THYROID PEROXIDASE THE GENE AND PROTEIN STRUCTURE OF THYROID PEROXIDASE FUNCTIONAL CHARACTERIZATION OF THYROID PEROXIDASE EXPRESSION AND REGULATION OF THYROID PEROXIDASE MUTATIONS IN THYROID PEROXIDASE THE HYDROGEN PEROXIDE–GENERATING SYSTEM CLONING OF THE DUAL OXIDASE AND THE DUAL OXIDASE MATURATION FACTOR GENES THE PROTEIN STRUCTURE OF DUAL OXIDASES AND THE DUAL OXIDASE MATURATION FACTORS EXPRESSION AND REGULATION OF DUAL OXIDASES AND THE DUAL OXIDASE MATURATION FACTORS MECHANISM OF HYDROGEN PEROXIDE GENERATION REGULATION OF HYDROGEN PEROXIDE ACTIVITY GENETIC DEFECTS IN HYDROGEN PEROXIDE GENERATION IODINATION AND THYROID HORMONE SYNTHESIS OXIDATION OF THYROID PEROXIDASE TO COMPOUND I AND COMPOUND II OXIDATION OF IODIDE IODINATION AND COUPLING OF TYROSYL RESIDUES INHIBITION OF THYROID PEROXIDASE BY THIONAMIDE DRUGS CELLULAR UPTAKE AND PROTEOLYSIS OF THYROGLOBULIN SECRETION OF THYROID HORMONES DEHALOGENATION OF MONOIODOTYROSINE AND DIIODOTYROSINE IODOTYROSINE (IYD/DEHAL1) DEIODINASE GENE AND PROTEIN DEHALOGENASE DEFICIENCY REFERENCES C. Peripheral Thyroid Hormone Binding and Metabolism Chapter 5: Thyroid hormone transport proteins EVOLUTIONARY CONSIDERATIONS FUNCTIONS OF THBPs CLINICAL CONSIDERATIONS THYROID-BINDING GLOBULIN STRUCTURE AND FUNCTION PHYSIOLOGIC REGULATION OF TBG IN HUMANS PATHOLOGY HUMAN SERPINA7 GENE SEQUENCE VARIANTS AFFECTING TBG CONCENTRATION OR FUNCTION TRANSTHYRETIN STRUCTURE AND FUNCTION PHYSIOLOGIC REGULATION OF TTR IN HUMANS PATHOLOGY HUMAN TTR GENE SEQUENCE VARIANTS AFFECTING TTR CONCENTRATION OR FUNCTION DYSTRANSTHYRETINEMIC HYPERTHYROXINEMIA ALBUMIN STRUCTURE AND FUNCTION PATHOPHYSIOLOGY HUMAN ALB GENE VARIANTS AFFECTING ALB CONCENTRATION OR FUNCTION p.Arg242His OTHER SEQUENCE VARIANTS AT Arg242 p.Arg246Ile T3 VARIANTS OF FDH MINOR CARRIERS CLINICAL IMPLICATIONS OF THBPs REFERENCES Chapter 6: Intracellular pathways of iodothyronine metabolism/implications of deiodination for thyroid hormone action STRUCTURE OF THE DEIODINASES TOPOLOGY AND SUBCELLULAR LOCALIZATION STRUCTURE–FUNCTION RELATIONSHIPS OF DEIODINASES AND MECHANISM OF DEIODINATION SPECIFIC PROPERTIES OF THE DEIODINASES TYPE 1 DEIODINASE TYPE 2 DEIODINASE TYPE 3 DEIODINASE NONDEIODINATIVE METABOLISM OF IODOTHYRONINES PHYSIOLOGIC ROLES OF THE SELENODEIODINASES DEIODINASES AND THE REGULATION OF T3 PRODUCTION ADAPTATION TO HYPOTHYROIDISM INTRACELLULAR TRIIODOTHYRONINE HOMEOSTASIS DEIODINASES AND REGULATION OF THYROTROPIN SECRETION DEIODINASES AND THE BIOLOGIC EFFECTS OF THYROID HORMONE DEIODINASES AND THE CENTRAL NERVOUS SYSTEM DEIODINASES AND THE SKELETON DEIODINASES AND METABOLISM DEVELOPMENTAL ROLES OF THE DEIODINASES MATERNAL–FETAL PHYSIOLOGY TRIIODOTHYRONINE MODULATION OF PLACENTAL THYROID HORMONE TRANSFER D3 EXPRESSION AND THE REQUIREMENT FOR THYROXINE IN NORMAL PREGNANCY THE DEIODINASES IN HUMAN PATHOPHYSIOLOGY NONTHYROIDAL ILLNESS CONSUMPTIVE HYPOTHYROIDISM DEIODINASES IN CANCER HYPERTHYROIDISM AND OVEREXPRESSION OF DEIODINASES DEIODINASES IN THE ISCHEMIC HEART DEIODINASES IN LUNG INJURY CONCLUSION ACKNOWLEDGMENT REFERENCES D. Thyroid Hormone Action Chapter 7: Intracellular actions by thyroid hormones THYROID HORMONE TRANSPORT AND METABOLISM TR-DEPENDENT SIGNALING OF TH WITH DIRECT BINDING TO DNA (TYPE 1) THYROID HORMONE RESPONSE ELEMENTS TRANSCRIPTIONAL REGULATION BY TRs THYROID HORMONE RECEPTOR–INTERACTING COREPRESSORS/BASAL REPRESSION THYROID HORMONE RECEPTOR–INTERACTING COACTIVATORS/TRANSCRIPTIONAL ACTIVATION NEGATIVE REGULATION BY TRs POSTTRANSLATIONAL MODIFICATION OF TR RESISTANCE TO TH THYROID HORMONE RECEPTOR ISOFORM KNOCKOUT AND KNOCKIN MICE TRANSCRIPTIONAL CASCADES TR-DEPENDENT SIGNALING OF TH WITH INDIRECT BINDING TO DNA (TYPE 2) TR-DEPENDENT SIGNALING OF TH WITHOUT DNA BINDING (TYPE 3) TR-INDEPENDENT TH SIGNALING (TYPE IV) TH ANALOGS, DISRUPTORS, AND METABOLITES SUMMARY REFERENCES Chapter 8: Thyroid hormone structure–function relationships THYROID HORMONE STRUCTURE, METABOLISM, AND ACTIVITY TR ACTIVATION BY NATURAL AND SYNTHETIC AGONISTS DEVELOPMENT OF SELECTIVE TR SUBTYPE AGONISTS STRUCTURE–FUNCTION RELATIONSHIPS AT TR MUTANTS—THE ISSUE OF TH RESISTANCE TR ANTAGONISM THYROID HORMONE INTERACTIONS WITH ALTERNATE RECEPTORS AND BINDING PROTEINS THYRONAMINES AND ANALOGS CONCLUSION REFERENCES E. Factors That Control Thyroid Function Chapter 9: Chemistry and biosynthesis of thyrotropin CHEMISTRY GENES ENCODING THE SUBUNITS OF THYROTROPIN CHROMOSOME LOCALIZATION STRUCTURE OF THE COMMON α-SUBUNIT GENE STRUCTURE OF THE THYROTROPIN-β–SUBUNIT GENE CENTRAL HYPOTHYROIDISM DUE TO THYROTROPIN-β–SUBUNIT GENE ABNORMALITIES PRETRANSLATIONAL REGULATION OF THYROTROPIN BIOSYNTHESIS NEGATIVE REGULATORS POSITIVE REGULATORS SUMMARY OF PRETRANSLATION REGULATION OF THE HUMAN COMMON α- AND TSH-β–SUBUNIT GENE EXPRESSION POSTTRANSLATIONAL PROCESSING OF THYROTROPIN IN VITRO TRANSLATION OF THYROTROPIN-β–SUBUNIT AND α-SUBUNIT MESSENGER RNA BIOSYNTHESIS OF THYROTROPIN IN INTACT CELLS PROCESSING OF HIGH-MANNOSE PRECURSOR OLIGOSACCHARIDES TERMINAL SULFATION AND SIALYLATION OF COMPLEX OLIGOSACCHARIDES DEVELOPMENTAL AND ENDOCRINE REGULATION OF THYROTROPIN GLYCOSYLATION BIOACTIVITY AND METABOLIC CLEARANCE OF THYROTROPIN THREE-DIMENSIONAL CONFORMATION OF THYROTROPIN RECOMBINANT HUMAN THYROTROPIN REFERENCES Chapter 10: The thyrotropin receptor THE STRUCTURE OF THE THYROTROPIN RECEPTOR THE THYROTROPIN RECEPTOR GENE RECOGNITION OF THE RECEPTOR BY THYROTROPIN PROPOSED MECHANISM OF ACTIVATION OF THE RECEPTOR BY TSH ACTIVATION BY THYROSTIMULIN ACTIVATION BY CHORIONIC GONADOTROPIN ACTIVATION BY THYROTROPIN-RECEPTOR ANTIBODIES ACTIVATION BY LOW–MOLECULAR-WEIGHT DRUG-LIKE CHEMICALS DOWNREGULATION OF THE THYROTROPIN RECEPTOR REFERENCES Chapter 11: Aging and the thyroid CHANGES IN THYROID ANATOMY WITH AGE PHYSIOLOGIC CHANGES IN THYROID FUNCTION WITH AGE CHALLENGES IN THE DIAGNOSIS AND MANAGEMENT OF THYROID DYSFUNCTION WITH AGE CHALLENGES IN THE DIAGNOSIS AND MANAGEMENT OF NODULAR DISEASE AND THYROID CANCER SUMMARY REFERENCES Chapter 12: Effects of drugs on TSH secretion, thyroid hormones’ absorption, synthesis, metabolism, and action INTRODUCTION DRUGS THAT ALTER SERUM TSH LEVELS (FIG. 12-1, PANEL 1) DOPAMINE/DOPAMINE AGONISTS AND ANTAGONISTS SOMATOSTATIN AND SOMATOSTATIN ANALOGS REXINOIDS OTHER DRUGS THAT SUPPRESS TSH SECRETION DRUGS THAT REDUCE THYROID HORMONE ABSORPTION BILE ACID SEQUESTRANTS FERROUS SULFATE SUCRALFATE AND ALUMINUM-CONTAINING ANTACIDS CALCIUM CARBONATE AND PHOSPHATE BINDERS OTHER MEDICATIONS THAT MAY REDUCE T4 INTESTINAL ABSORPTION DRUGS THAT REDUCE SYNTHESIS AND SECRETION OF THYROID HORMONES (FIG. 12-1, PANEL 2) THIONAMIDES (ANTITHYROID DRUGS) IONIC INHIBITORS (PERCHLORATE, THIOCYANATE; SEE Chapter 13 ON THYROID DISRUPTORS) LITHIUM DRUGS THAT ALTER THE METABOLISM OF THYROID HORMONES (FIGS. 12-1, PANEL 3 AND 12-2) DRUGS THAT INDUCE CYP3a (PHENYTOIN, CARBAMAZEPINE, PHENOBARBITAL, RIFAMPIN, RITONAVIR, SERTRALINE) DRUGS THAT INHIBIT THE DEIODINATION OF T4 AND T3 PROPYLTHIOURACIL PROPRANOLOL AND NADOLOL DRUGS THAT ALTER THE TRANSPORT OR ACTION OF THYROID HORMONES (FIG. 12-1, PANEL 3) NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (SALICYLATES, SALSALATE, FENCLOFENAC) FUROSEMIDE HEPARIN AND FATTY ACIDS ESTROGEN AND SELECTIVE ESTROGEN MODULATORS (SERM) (TAMOXIFEN, RALOXIFENE) ANDROGENS OTHER DRUGS ALTERING TBG LEVELS DRUGS ACTING AT MULTIPLE SITES TO ALTER THYROID HORMONE HOMEOSTASIS IODINATED RADIOGRAPHIC CONTRAST AGENTS PHENYTOIN AMIODARONE GLUCOCORTICOIDS CYTOKINES (INTERFERON, INTERLEUKIN, AND TUMOR NECROSIS FACTOR) TYROSINE KINASE INHIBITORS DRUGS ALTERING THYROID FUNCTION THROUGH ALTERATIONS IN IMMUNITY IMMUNE RECONSTITUTION SYNDROME ANTI-CD52 ANTIBODY ALEMTUZUMAB CHECKPOINT INHIBITORS REFERENCES Chapter 13: Thyroid disruptors INTRODUCTION SUBSTANCES THAT INHIBIT THYROIDAL IODINE UPTAKE PERCHLORATE THIOCYANATE NITRATE COMPOUNDS WITH DIRECT ACTIONS ON THE THYROID HORMONE RECEPTOR POLYCHLORINATED BIPHENYLS POLYBROMINATED DIPHENYL ETHERS BISPHENOL-A AND PHTHALATES TRICLOSAN COMPOUNDS THAT DISPLACE T4 FROM SERUM THYROID BINDING PROTEINS PCBs AND PBDEs COMPOUNDS THAT INHIBIT THYROPEROXIDASE ACTIVITY ISOFLAVONES COMPOUNDS THAT DECREASE T4 HALF-LIFE BY ACTIVATING HEPATIC ENZYMES ORGANOCHLORINE PESTICIDES DIOXINS AND FURANS COMPOUNDS THAT INHIBIT DEIODINASE ACTIVITY OTHER EXPOSURES STYRENES PERFLUORINATED AND GEN X COMPOUNDS ORGANOPHOSPHATE PESTICIDES SUNSCREENS LEAD SUMMARY REFERENCES Chapter 14: Nonthyroidal illness syndrome INTRODUCTION DESCRIPTION OF NTIS CHANGES IN SERUM THYROID HORMONE AND THYROTROPIN CONCENTRATIONS CHANGES IN THYROID HORMONE KINETICS CHANGES IN THE HYPOTHALAMIC–PITUITARY–THYROID AXIS CHANGES IN PERIPHERAL THYROID HORMONE METABOLISM PATHOGENESIS OF NTIS PATHOGENESIS OF CHANGES IN THE HYPOTHALAMIC–PITUITARY–THYROID AXIS CHANGES IN HPT AXIS DURING FASTING CHANGES IN HPT AXIS DURING ILLNESS PATHOGENESIS OF CHANGES IN PERIPHERAL THYROID HORMONE METABOLISM CHANGES IN SERUM IODOTHYRONINE–BINDING PROTEINS CHANGES IN IODOTHYRONINE TRANSPORT INTO TISSUES CHANGES IN IODOTHYRONINE DEIODINASES CHANGES IN IODOTHYRONINE NUCLEAR RECEPTORS CLINICAL RELEVANCE OF NTIS PROGNOSTIC IMPORTANCE OF NTIS DIAGNOSIS OF THYROID DISEASE IN NTIS TREATMENT OF PATIENTS WITH NTIS SPECIFIC TYPES OF NTIS CHRONIC RENAL FAILURE LIVER DISEASE HUMAN IMMUNODEFICIENCY VIRUS INFECTION PSYCHIATRIC DISEASE CONCLUSION REFERENCES Chapter 15: Iodine deficiency and excess, endemic cretinism INTRODUCTION THE ECOLOGY OF IODINE DIETARY SOURCES, ABSORPTION, AND METABOLISM OF IODINE GOITROGENS IODINE REQUIREMENTS ADULTHOOD PREGNANCY AND LACTATION INFANCY AND CHILDHOOD ASSESSMENT OF IODINE DEFICIENCY URINARY IODINE CONCENTRATION BREAST MILK IODINE CONCENTRATION THYROID SIZE THYROID-STIMULATING HORMONE AND THYROID HORMONES THYROGLOBULIN EFFECTS OF IODINE DEFICIENCY THYROIDAL ADAPTATION TO IODINE DEFICIENCY EFFECTS OF HYPOTHYROIDISM DUE TO IODINE DEFICIENCY ON THE DEVELOPING BRAIN CRETINISM THE BENEFITS OF CORRECTION OF IODINE DEFICIENCY IODINE INTERVENTIONS IN SEVERELY DEFICIENT PREGNANT WOMEN IODINE INTERVENTIONS IN MILD TO MODERATELY DEFICIENT PREGNANT WOMEN INFANCY CHILDHOOD ADULTHOOD THYROID CANCER EPIDEMIOLOGY TREATMENT AND PREVENTION SALT FORTIFICATION WITH IODINE IODINE SUPPLEMENTATION EFFECTS OF EXCESS IODIDE PHYSIOLOGIC RESPONSE TO EXCESS IODIDE TOLERABLE UPPER LIMITS FOR IODINE INTAKE MONITORING OF IODINE EXCESS IN POPULATIONS SOURCES OF EXCESS IODIDE IODINE-INDUCED HYPOTHYROIDISM OR GOITER IN THE ABSENCE OF APPARENT UNDERLYING THYROID DISEASE IODINE AND THYROIDITIS IODINE-INDUCED THYROTOXICOSIS AMIODARONE-INDUCED THYROID DISEASE (SEE Chapter 11) REFERENCES Section II: Assessment of Thyroid Structure and Function Chapter 16: Physical examination of the thyroid gland HISTORY PHYSICAL EXAMINATION INSPECTION PALPATION FACING THE PATIENT STANDING BEHIND THE PATIENT AUSCULTATION PALPATING LOBES AND EVALUATING THYROID SIZE THYROID NODULES HEMIAGENESIS CONSISTENCY PAIN/TENDERNESS LYMPHADENOPATHY DISTINGUISHING BENIGN FROM MALIGNANT DISEASE REFERENCES Chapter 17: Laboratory measurement of thyroid-related hormones, proteins, and autoantibodies in serum INTRODUCTION NOMENCLATURE FOR SENSITIVITY AND ASSESSMENT OF ASSAYS FUNCTIONAL VERSUS ANALYTICAL SENSITIVITY OF ASSAYS THYROID-STIMULATING HORMONE METHODS FOR SERUM TSH MEASUREMENTS REQUIREMENTS FOR SERUM TSH MEASUREMENTS TSH ISOFORMS INDICATIONS FOR TRH TESTING TSH REFERENCE INTERVALS THE CLINICAL UTILITY OF TSH MEASUREMENT TSH AND THYROID FUNCTION ASSESSMENT IN PREGNANCY (SEE Chapter 66) HOSPITALIZED PATIENTS THYROID HORMONE MEASUREMENTS SERUM TOTAL THYROID HORMONE (TT4 AND TT3) ASSAY METHODOLOGY CLINICAL UTILITY OF TT4 AND TT3 MEASUREMENTS TT4 AND TT3 REFERENCE INTERVALS SERUM FREE THYROID HORMONE TESTS (FT4 AND FT3) DIRECT FT4 AND FT3 METHODS INDIRECT FT4 AND FT3 ESTIMATE TESTS SERUM-FREE THYROXINE AND FREE TRIIODOTHYRONINE INDEXES THYROID HORMONE–BINDING PROTEINS FAMILIAL DYSALBUMINEMIC AND TRANSTHYRETIN-ASSOCIATED HYPERTHYROXINEMIAS SERUM THYROGLOBULIN (Tg) REQUIREMENTS FOR SERUM Tg METHODS FACTORS THAT INFLUENCE CIRCULATING Tg CONCENTRATIONS ANALYTICAL AND TECHNICAL CONSIDERATION THYROID-SPECIFIC AUTOANTIBODIES ANTI–TSH RECEPTOR AUTOANTIBODIES ANTITHYROID PEROXIDASE AUTOANTIBODIES ANTITHYROGLOBULIN AUTOANTIBODIES INTERFERENCES WITH THYROID TEST OUTCOMES INTERFERENCES WITH THYROID MEASUREMENT METHODOLOGIES ASSAY INTERFERENCES AUTOMATION OF THYROID TESTS REFERENCES Chapter 18: Nonisotopic thyroid imaging INTRODUCTION PLAIN RADIOGRAPHY ULTRASONOGRAPHY BASIC PHYSICS AND TECHNICAL PRINCIPLES (1) CONDUCTING THE EXAMINATION CLINICAL APPLICATIONS DEVELOPMENTAL ABNORMALITIES THE NORMAL THYROID GLAND GOITER DIFFUSE NONNEOPLASTIC THYROID DISEASES NODULES AND MULTINODULAR GOITER INTERVENTIONAL PROCEDURES COMPUTED TOMOGRAPHY BASIC PHYSICS PRINCIPLES (22) THE NORMAL THYROID GLAND DIFFUSE THYROID DISEASE INCIDENTALOMAS CT IN LARGE BENIGN GOITERS ECTOPIC THYROID TISSUE CT AND PREOPERATIVE PLANNING OF THYROID CARCINOMAS, LYMPHOMAS, AND METASTASIS CT AND FOLLOW-UP OF THYROID CARCINOMAS MAGNETIC RESONANCE IMAGING BASIC PHYSICS PRINCIPLES (41) NORMAL THYROID TISSUE DIFFUSE THYROID DISEASE THYROID INCIDENTALOMAS AND NODULE CHARACTERIZATION PREOPERATIVE PLANNING OF THYROID CARCINOMAS: ASSESSING INVASION (48) FOLLOW-UP OF THYROID CARCINOMAS CONCLUSION REFERENCES Chapter 19: Thyroid radionuclide uptake and imaging studies INTRODUCTION RADIOPHARMACEUTICALS MODALITIES RADIOIODINE UPTAKE STUDIES PLANAR IMAGING: HYPERTHYROIDISM PLANAR IMAGING: THYROID CANCER TOMOGRAPHY DOSIMETRY FDG PET/CT IN THYROID CANCER FDG PET/CT IN INCIDENTAL THYROID DISEASE IMAGING OF MEDULLARY THYROID CANCER CONCLUSIONS REFERENCES Chapter 20: Cytopathology of the thyroid gland INTRODUCTION SPECIMEN PREPARATIONS THYROID FNA CLASSIFICATION NONDIAGNOSTIC OR UNSATISFACTORY (CATEGORY I) BENIGN (CATEGORY II) ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDETERMINED SIGNIFICANCE (AUS/FLUS) (CATEGORY III) FOLLICULAR OR ONCOCYTIC (HüRTHLE-CELL) NEOPLASM OR SUSPICIOUS FOR FOLLICULAR OR ONCOCYTIC (HüRTHLE-CELL) NEOPLASM (CATEGORY IV) SUSPICIOUS FOR MALIGNANCY (CATEGORY V) MALIGNANT (CATEGORY VI) CORE NEEDLE BIOPSY KEY CYTOMORPHOLOGIC FEATURES OF THYROID FINE-NEEDLE ASPIRATION DIAGNOSES DIFFUSE TOXIC GOITER CHRONIC LYMPHOCYTIC THYROIDITIS (11,15) ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDETERMINED SIGNIFICANCE (AUS/FLUS) SUSPICIOUS FOR FOLLICULAR NEOPLASM/FOLLICULAR NEOPLASM (INCLUDING TUMORS WITH ONCOCYTIC FEATURES) MALIGNANT LESIONS PAPILLARY THYROID CARCINOMA AND ITS VARIANTS MEDULLARY THYROID CARCINOMA POORLY DIFFERENTIATED CARCINOMA ANAPLASTIC CARCINOMA ROLE OF ANCILLARY STUDIES IN THE DIAGNOSIS OF THYROID TUMORS IN CYTOLOGIC SPECIMENS’ IMMUNOHISTOCHEMISTRY REFERENCES Chapter 21: Histopathology of the thyroid gland NORMAL THYROID PATHOLOGIC DIAGNOSIS OF THYROID LESIONS DEVELOPMENTAL VARIATIONS GOITER GRAVES DISEASE/DIFFUSE TOXIC GOITER DYSHORMONOGENETIC GOITER IATROGENIC AND RELATED HYPERPLASIAS AUTOIMMUNE THYROIDITIS SILENT THYROIDITIS SPECIFIC INFECTIOUS THYROIDITIS GRANULOMATOUS THYROIDITIS PALPATION THYROIDITIS AMIODARONE INJURY WITH THYROTOXICOSIS RIEDEL THYROIDITIS (AKA RIEDEL STRUMA) COMBINED RIEDEL STRUMA AND FIBROSING HASHIMOTO THYROIDITIS MISCELLANEOUS DISORDERS RADIATION EFFECTS AMYLOIDOSIS BLACK THYROID NEOPLASMS BENIGN NEOPLASMS ADENOMAS AND ADENOMATOUS NODULES MALIGNANT NEOPLASMS PAPILLARY CARCINOMA FOLLICULAR CARCINOMA HÜRTHLE-CELL NEOPLASM/ONCOCYTIC FOLLICULAR NEOPLASM PATHOLOGIC DIAGNOSIS OF PAPILLARY AND FOLLICULAR CARCINOMA OF THYROID: CONTROVERSIES CLEAR CELL TUMORS HIGH-GRADE THYROID CARCINOMA POORLY DIFFERENTIATED THYROID CARCINOMA ANAPLASTIC CARCINOMA SQUAMOUS CELL CARCINOMA, MUCOEPIDERMOID CARCINOMA, AND INTRATHYROIDAL THYMOMA-LIKE NEOPLASMS MEDULLARY THYROID CARCINOMA CALCITONIN NEGATIVE NEUROENDOCRINE CARCINOMA OF THYROID LYMPHOMA SARCOMA CARCINOMA IN ECTOPIC THYROID TISSUE METASTATIC NEOPLASMS REFERENCES Section III: Thyroid Diseases: Thyrotoxicosis A. Causes of Thyrotoxicosis Chapter 22: Pathogenesis of Graves disease INTRODUCTION AUTOIMMUNITY DEFINITION OF AN AUTOANTIGEN THE NATURE OF T CELLS ANTIBODY AND T-CELL INTERACTIONS WITH ANTIGEN SECOND SIGNALS CRITERIA FOR AN AUTOIMMUNE DISEASE RESTRICTION VERSUS POLYCLONALITY THYROID IMMUNOLOGY INTRATHYROIDAL B CELLS AUTOANTIBODIES TO THE HUMAN TSHR BIOACTIVITY OF TSHR ANTIBODIES PREVALENCE OF TSHR ANTIBODIES IN GRAVES DISEASE IMMUNOLOGIC CHARACTERISTICS OF TSHR ANTIBODIES TSHR FUNCTION IN GRAVES DISEASE LESSONS FROM MONOCLONAL TSHR ANTIBODIES WITH STIMULATING ACTIVITY OTHER THYROID ANTIBODIES IN GRAVES DISEASE THE INTRATHYROIDAL LYMPHOCYTIC INFILTRATE FUNCTIONAL ANALYSIS OF INTRATHYROIDAL T CELLS T-CELL SELECTION APOPTOSIS IN GRAVES DISEASE THE INTRATHYROIDAL T-CELL RECEPTOR V GENE REPERTOIRE REGULATORY EFFECTS OF T CELLS IN AUTOIMMUNE THYROID DISEASE THE Th17 CELLS IMMUNE MECHANISMS IN THE PATHOGENESIS OF GRAVES DISEASE FAILURE OF IMMUNE CELL DELETION AND/OR SUPPRESSION SPECIFICITY CROSSOVER (MOLECULAR MIMICRY) BYSTANDER EFFECTS EPIGENETIC CHANGES THYROID CELL EXPRESSION OF HLA MOLECULES ANIMAL MODELS OF GRAVES DISEASE KNOWN RISK FACTORS FOR PRECIPITATING GRAVES DISEASE (TABLE 22-5) SUSCEPTIBILITY GENES INFECTION THYROID AUTOANTIBODIES THYROID TISSUE DAMAGE STRESS SEX STEROIDS THE X CHROMOSOME THE POSTPARTUM PERIOD MATERNAL MICROCHIMERISM IODINE IRRADIATION OVERVIEW OF THE ETIOLOGY OF GRAVES DISEASE REFERENCES Chapter 23: Thyrotropin-induced thyrotoxicosis INTRODUCTION EPIDEMIOLOGY PATHOLOGIC AND PATHOGENIC ASPECTS SIGNS AND SYMPTOMS LABORATORY AND BIOCHEMICAL FEATURES SERUM THYROTROPIN AND THYROID HORMONE LEVELS PITUITARY GLYCOPROTEIN HORMONE α-SUBUNIT PARAMETERS OF PERIPHERAL THYROID HORMONE ACTION DIAGNOSTIC TESTING IMAGING STUDIES AND LOCALIZATION DIFFERENTIAL DIAGNOSIS TREATMENT AND OUTCOME CRITERIA OF CURE AND FOLLOW-UP REFERENCES Chapter 24: Toxic adenoma and toxic multinodular goiter EPIDEMIOLOGY CLINICAL ASPECTS OF THYROID AUTONOMY DIAGNOSIS OF THYROID AUTONOMY NATURAL HISTORY MORPHOLOGY ETIOLOGY LESSONS FROM EPIDEMIOLOGIC STUDIES FROM HYPERPLASTIC GROWTH TO NODULAR TRANSFORMATION TRANSFORMATION TO HOT THYROID NODULES TREATMENT OF AUTONOMOUS THYROID NODULES (SEE CHAPTER 32) SURGERY RADIOIODINE THERAPY COST-EFFECTIVE MANAGEMENT OF THYROID AUTONOMY FOLLOW-UP ACKNOWLEDGMENT REFERENCES Chapter 25: Trophoblastic tumors INTRODUCTION HUMAN CHORIONIC GONADOTROPIN GRADATIONS OF SEVERITY CLINICAL FEATURES DIAGNOSIS HYPEREMESIS GRAVIDARUM MUTANT THYROID-STIMULATING HORMONE RECEPTOR THERAPY REFERENCES Chapter 26: Sporadic painless, painful subacute and acute infectious thyroiditis INTRODUCTION DESTRUCTION-INDUCED THYROIDITIS PAINFUL THYROID SPORADIC PAINLESS THYROIDITIS ETIOLOGY CLINICAL MANIFESTATIONS LABORATORY FINDINGS CYTOLOGY IMAGING PATHOLOGY DIFFERENTIAL DIAGNOSIS CLINICAL MANAGEMENT SUBACUTE THYROIDITIS ETIOLOGY INFECTIOUS ASSOCIATION AUTOIMMUNE ASSOCIATION GENETIC ASSOCIATION CLINICAL MANIFESTATIONS LABORATORY FINDINGS CYTOLOGY IMAGING PATHOLOGY DIFFERENTIAL DIAGNOSIS CLINICAL MANAGEMENT ACUTE INFECTIOUS THYROIDITIS ETIOLOGY BACTERIAL INFECTIONS FUNGAL INFECTIONS MYCOBACTERIAL INFECTIONS PARASITIC INFECTIONS SYPHILITIC INFECTIONS THYROIDAL INFECTIONS IN IMMUNOCOMPROMISED PATIENTS CLINICAL MANIFESTATIONS LABORATORY FINDINGS CYTOLOGY IMAGING STUDIES CLINICAL MANAGEMENT REFERENCES Chapter 27: Thyrotoxicosis of extrathyroidal origin INTRODUCTION EXOGENOUS THYROID HORMONE CAUSES CLINICAL PRESENTATION AND DIAGNOSIS TREATMENT THYROTOXICOSIS DUE TO METASTATIC THYROID CARCINOMA DEFINITION AND EPIDEMIOLOGY CLINICAL PRESENTATION AND DIAGNOSIS TREATMENT STRUMA OVARII DEFINITION AND EPIDEMIOLOGY CLINICAL PRESENTATION AND DIAGNOSIS TREATMENT ACKNOWLEDGMENT REFERENCES B. Organ System Manifestations Chapter 28: Overview of the clinical manifestations of thyrotoxicosis INTRODUCTION PREVALENCE OF CLINICAL FINDINGS ORGAN SYSTEM–SPECIFIC MANIFESTATIONS CENTRAL NERVOUS SYSTEM BEHAVIORAL HEALTH MANIFESTATIONS CARDIOVASCULAR MANIFESTATIONS PULMONARY MANIFESTATIONS GASTROINTESTINAL MANIFESTATIONS RENAL MANIFESTATIONS INTEGUMENTARY FINDINGS MUSCULOSKELETAL MANIFESTATIONS REPRODUCTIVE CHANGES HEMATOLOGIC MANIFESTATIONS MODULATING FACTORS AGE PREGNANCY COMORBIDITY ETIOLOGY OF THYROTOXICOSIS CLINICAL ASSESSMENT REFERENCES Chapter 29: Ophthalmopathy INTRODUCTION EPIDEMIOLOGY AND NATURAL HISTORY PATHOGENESIS RISK FACTORS AND PREVENTION CLINICAL PRESENTATION DIAGNOSIS TREATMENT OF HYPERTHYROIDISM IN PATIENTS WITH GO MANAGEMENT OF GO CONCLUSIONS REFERENCES Chapter 30: The cardiovascular system in thyrotoxicosis THYROID HORMONE ACTION ON THE HEART AND VASCULAR SYSTEM CLINICAL CONSEQUENCES OF THYROTOXICOSIS CARDIOVASCULAR SYMPTOMS AND SIGNS IN THYROTOXICOSIS ATRIAL FIBRILLATION ELECTROCARDIOGRAPHIC CHANGES HEART FAILURE HYPERTENSION AND VASCULAR DYSFUNCTION MAJOR ADVERSE CARDIOVASCULAR EVENTS ROLE OF OTHER HORMONES IN THYROTOXICOSIS SUBCLINICAL THYROTOXICOSIS AMIODARONE AND IODINE CONTAINING CONTRAST AGENTS REFERENCES Chapter 31: Thyroid hormones in intermediary metabolism, thermogenesis, and obesity THYROID HORMONE SIGNALING, TISSUE- AND TARGET GENE–SPECIFICITY IN RELATION TO INTERMEDIARY AND ENERGY METABOLISM THYROID HORMONE ACTION ON INTERMEDIARY METABOLISM CARBOHYDRATE METABOLISM CLINICAL CORRELATES PROTEIN METABOLISM CLINICAL CORRELATES LIPID METABOLISM CLINICAL CORRELATES THYROID HORMONE ACTION ON ENERGY METABOLISM THYROID HORMONE ACTION ON RESTING ENERGY EXPENDITURE THYROID HORMONE ACTION ON ADAPTIVE THERMOGENESIS THYROID HORMONE ACTION ON ACTIVITY-RELATED ENERGY EXPENDITURE THYROID HORMONE ACTION ON THERMIC EFFECT OF FOOD ENERGY STATUS AND THYROID HORMONE HOMEOSTASIS CLINICAL CORRELATES POTENTIAL USE OF THYROID HORMONE AS TREATMENT FOR WEIGHT LOSS AND DYSLIPIDEMIA CONCLUSIONS ACKNOWLEDGMENTS REFERENCES Chapter 32: The skeletal system in thyrotoxicosis REGULATION OF THYROID STATUS CONTROL OF INTRACELLULAR T3 AVAILABILITY MECHANISM OF THYROID HORMONE ACTION ROLE OF TSH IN BONE BONE REMODELING CYCLE SKELETAL CONSEQUENCES OF CHILDHOOD THYROTOXICOSIS SKELETAL EFFECTS OF THYROID HORMONES IN ADULTS POPULATION STUDIES IN NORMAL EUTHYROID INDIVIDUALS STUDIES OF ADULT THYROTOXICOSIS EFFECTS OF TREATMENT FOR THYROTOXICOSIS SUBCLINICAL HYPERTHYROIDISM PATIENTS TREATED WITH SUPPRESSIVE DOSES OF THYROXINE REFERENCES Chapter 33: Thyroid dermopathy and thyroid acropachy THYROID DERMOPATHY HISTOLOGIC FINDINGS IN THYROID DERMOPATHY CLINICAL MANIFESTATIONS PATHOGENESIS DIFFERENTIAL DIAGNOSIS TREATMENT OUTCOMES OF THERAPY OF THYROID DERMOPATHY FUTURE DIRECTIONS FOR THERAPY THYROID ACROPACHY REFERENCES Chapter 34: Psychiatric and cognitive effects of thyrotoxicosis INTRODUCTION NEUROPSYCHIATRIC MANIFESTATIONS OF OVERT THYROTOXICOSIS COGNITIVE MANIFESTATIONS OF OVERT THYROTOXICOSIS SUBCLINICAL THYROTOXICOSIS: NEUROPSYCHIATRIC AND COGNITIVE ASPECTS DIFFERENTIAL DIAGNOSIS: BEHAVIORAL SYNDROMES THAT MAY MIMIC THYROTOXICOSIS PSYCHOLOGICAL FACTORS IN THE PATHOPHYSIOLOGY OF THYROTOXICOSIS TREATMENT OF THYROTOXICOSIS: NEUROPSYCHIATRIC ASPECTS POSSIBLE LINK BETWEEN THYROID HORMONE AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER USE OF THYROID HORMONE IN AFFECTIVE DISORDERS LITHIUM AND THYROID FUNCTION REFERENCES Chapter 35: Thyrotoxic storm CLINICAL FEATURES LABORATORY FINDINGS PATHOGENESIS TREATMENT THERAPY TO REDUCE THYROID HORMONE SYNTHESIS AND SECRETION THERAPY DIRECTED AGAINST SYSTEMIC DISTURBANCES THERAPY DIRECTED AGAINST THE PERIPHERAL ACTIONS OF THYROID HORMONE THERAPY DIRECTED AGAINST PRECIPITATING ILLNESS REFERENCES C. Diagnosis and Management of Thyrotoxicosis Chapter 36: Diagnosis of thyrotoxicosis INTRODUCTION CLINICAL DIAGNOSIS CLUES FROM ROUTINE LABORATORY TESTS LABORATORY TESTING FOR THYROTOXICOSIS SERUM THYROXINE DETERMINATIONS SERUM TRIIODOTHYRONINE DETERMINATIONS SERUM THYROTROPIN DETERMINATIONS SCREENING, CASE FINDING, AND DIAGNOSIS DIAGNOSING THE CAUSE OF THYROTOXICOSIS REFERENCES Chapter 37: Treatment of thyrotoxicosis INTRODUCTION THYROTOXICOSIS CAUSED BY GRAVES DISEASE DRUG THERAPY OF THYROTOXICOSIS CAUSED BY GRAVES DISEASE ANTITHYROID DRUGS (Fig. 37-1) MECHANISMS OF ACTION INTRATHYROIDAL ACTIONS EXTRATHYROIDAL ACTIONS EFFECTS ON THE IMMUNE SYSTEM CLINICAL PHARMACOLOGY OF THE ANTITHYROID DRUGS METHIMAZOLE PROPYLTHIOURACIL CLINICAL CONSIDERATIONS IN THE USE OF ANTITHYROID DRUGS SIDE EFFECTS OF ANTITHYROID DRUGS FOLLOW-UP OF PATIENTS TAKING AN ANTITHYROID DRUG FOR GRAVES DISEASE REMISSIONS AND ANTITHYROID DRUG THERAPY THERAPY FACTORS RELATING TO REMISSION OF GRAVES DISEASE DISCONTINUATION OF ANTITHYROID DRUG THERAPY OTHER DRUGS USED IN THE TREATMENT OF THYROTOXICOSIS CAUSED BY GRAVES DISEASE INORGANIC IODIDE ORAL CHOLECYSTOGRAPHIC AGENTS β-ADRENERGIC ANTAGONIST DRUGS RADIOACTIVE IODINE THERAPY FOR THYROTOXICOSIS (Fig. 37-1) PRACTICAL THERAPEUTIC CONSIDERATIONS COMPLICATIONS AND POTENTIAL RISKS OF RADIOIODINE THERAPY POSTRADIOIODINE WORSENING OF THYROID FUNCTION RADIOIODINE THERAPY AND GRAVES OPHTHALMOPATHY INDICATIONS FOR RADIOIODINE THERAPY SURGICAL THERAPY FOR THYROTOXICOSIS (Fig. 37-1) SPECIAL CONSIDERATIONS IN THE TREATMENT OF THYROTOXICOSIS TREATMENT OF CHILDREN AND ADOLESCENTS TREATMENT OF ELDERLY PATIENTS THYROTOXICOSIS IN PREGNANT WOMEN AND DURING LACTATION THYROTOXIC STORM THYROTOXICOSIS DUE TO TOXIC ADENOMA AND MULTINODULAR GOITER TOXIC ADENOMA TOXIC MULTINODULAR GOITER REFERENCES Chapter 38: Subclinical thyrotoxicosis ETIOLOGY ENDOGENOUS SUBCLINICAL THYROTOXICOSIS EXOGENOUS SUBCLINICAL THYROTOXICOSIS EVALUATION DIFFERENTIAL DIAGNOSIS EPIDEMIOLOGY AND NATURAL HISTORY CLINICAL AND BIOLOGIC IMPORTANCE PHYSIOLOGY OF SUPPRESSION OF TSH SECRETION CARDIOVASCULAR CONSEQUENCES BONE AND MINERAL METABOLISM COGNITIVE DYSFUNCTION AND DEMENTIA TREATMENT CHOICE OF TREATMENT MODALITY SIDE EFFECTS OF TREATMENT FOR SUBCLINICAL THYROTOXICOSIS FUTURE DIRECTIONS REFERENCES Section IV: Thyroid Diseases: Hypothyroidism A. Causes of Hypothyroidism Chapter 39: Chronic autoimmune thyroiditis INTRODUCTION PREDISPOSITION TO CHRONIC AUTOIMMUNE THYROIDITIS PATHOGENESIS OF CHRONIC AUTOIMMUNE THYROIDITIS ANTIGEN PRESENTATION T-CELL RESPONSES B-CELL RESPONSES EFFECTOR MECHANISMS EXPERIMENTAL AUTOIMMUNE THYROIDITIS CLINICAL ASPECTS ASSOCIATED DISORDERS REFERENCES Chapter 40: Genetic defects causing hypothyroidism MONOGENIC CAUSES OF THYROID DYSGENESIS KEY TRANSCRIPTION FACTOR MUTATIONS IN TD NKX2-1 PAX8 FOXE1 GLIS3 TSHR ADDITIONAL GENES ASSOCIATED WITH TD NKX2-5 JAG1 CDCA8 (BOREALIN) TUBB1 NETRIN 1 (NTN1) SYNDROMES WHICH MAY BE ASSOCIATED WITH CH GENETIC CAUSES OF DYSHORMONOGENESIS THYROGLOBULIN TPO DUOX2 AND DUOXA2 IYD (PREVIOUSLY KNOWN AS DEHAL1) SLC5A5 (NIS) SLC26A4 (PENDRIN) SLC26A7 EVIDENCE FOR AN UNDIAGNOSED GENETIC COMPONENT IN TD REFERENCES Chapter 41: Primary hypothyroidism due to other causes INTRODUCTION RADIOACTIVE IODINE (131I THERAPY) THYROIDECTOMY TREATMENT OF TOXIC NODULAR GOITER TREATMENT OF NONTOXIC NODULAR GOITER EXTERNAL RADIATION HYPOTHYROIDISM DUE TO THERAPEUTIC PHARMACOLOGIC AGENTS LITHIUM CARBONATE CYTOKINES AMIODARONE TYROSINE KINASE INHIBITORS IMMUNE CHECKPOINT INHIBITORS OTHER DRUGS HYPOTHYROIDISM DUE TO INFILTRATIVE DISORDERS RIEDEL THYROIDITIS (INVASIVE FIBROUS THYROIDITIS) AMYLOIDOSIS SARCOIDOSIS SCLERODERMA HEMOCHROMATOSIS CYSTINOSIS OTHER INFILTRATIVE OR INFECTIOUS DISORDERS (SEE CHAPTER 22) PRIMARY THYROID LYMPHOMA CONSUMPTIVE HYPOTHYROIDISM INDUSTRIAL AND ENVIRONMENTAL AGENTS (SEE CHAPTER 12) EMBRYOLOGIC VARIANTS LINGUAL THYROID (SEE CHAPTER 63) REFERENCES Chapter 42: Central hypothyroidism INTRODUCTION EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES AND DIAGNOSIS TREATMENT OF CeH REFERENCES B. Organ System Manifestations of Hypothyroidism Chapter 43: Overview of the clinical manifestations of hypothyroidism INTRODUCTION CLINICAL MANIFESTATIONS OVERT HYPOTHYROIDISM SUBCLINICAL HYPOTHYROIDISM CARDIOVASCULAR DISEASE AND MORTALITY PULMONARY SYSTEM NEUROPSYCHIATRIC FEATURES MUSCULOSKELETAL SYSTEM INFECTIOUS COMPLICATIONS SKIN AND CONNECTIVE TISSUE KIDNEYS AND ELECTROLYTE METABOLISM GASTROINTESTINAL TRACT AND LIVER HEMATOLOGY AND HEMOSTASIS PITUITARY DISORDERS IN HYPOTHYROIDISM ADRENAL DISORDERS IN HYPOTHYROIDISM SUMMARY REFERENCES Chapter 44: Hypothyroidism and the heart CLINICAL CONSEQUENCES OF HYPOTHYROIDISM CV SYMPTOMS AND SIGNS ELECTROCARDIOGRAPHIC CHANGES IN HYPOTHYROIDISM CORONARY ARTERY DISEASE IN HYPOTHYROIDISM CV RISK FACTORS IN HYPOTHYROIDISM LIPIDS BLOOD PRESSURE AND VASCULAR DYSFUNCTION THROMBOGENESIS SUBCLINICAL HYPOTHYROIDISM SPECIAL SITUATIONS IN HYPOTHYROIDISM RELATED TO THE HEART POSTACUTE MYOCARDIAL INFARCTION HEART FAILURE TREATMENT OF HYPOTHYROIDISM IN PATIENTS WITH CORONARY ARTERY DISEASE CARDIAC SURGERY AND CARDIAC TRANSPLANTATION PROCEDURES REFERENCES Chapter 45: The skeletal system in hypothyroidism PHYSIOLOGIC CONTROL OF THYROID HORMONE ACTION THYROID HORMONE TRANSPORT AND METABOLISM IN BONE THYROID HORMONE RECEPTOR FUNCTION IN BONE ROLE OF TSH ON SKELETAL GROWTH AND MATURATION SKELETAL DEVELOPMENT SKELETAL CONSEQUENCES OF CHILDHOOD HYPOTHYROIDISM SKELETAL CONSEQUENCES OF IMPAIRED SENSITIVITY TO THYROID HORMONE SKELETAL CONSEQUENCES OF ADULT HYPOTHYROIDISM A POSSIBLE ROLE FOR THYROID HORMONE SIGNALING IN OSTEOARTHRITIS REFERENCES Chapter 46: Psychiatric and cognitive effects of hypothyroidism INTRODUCTION PSYCHIATRIC AND COGNITIVE EFFECTS OF OVERT HYPOTHYROIDISM PSYCHIATRIC AND COGNITIVE EFFECTS OF SUBCLINICAL HYPOTHYROIDISM EFFECT OF THYROID FUNCTION VARIATIONS WITHIN THE NORMAL RANGE ON MOOD AND COGNITION HASHIMOTO ENCEPHALOPATHY REFERENCES Chapter 47: Myxedema Coma INTRODUCTION CLINICAL FEATURES: PRECIPITATING EVENTS GENERAL DESCRIPTION HYPOTHERMIA RESPIRATORY SYSTEM CARDIOVASCULAR MANIFESTATIONS GASTROINTESTINAL MANIFESTATIONS RENAL AND ELECTROLYTE MANIFESTATIONS NEUROPSYCHIATRIC MANIFESTATIONS INFECTIONS DIAGNOSIS TREATMENT VENTILATORY SUPPORT HYPONATREMIA HYPOTHERMIA HYPOTENSION GLUCOCORTICOID THERAPY THYROID HORMONE THERAPY COMMENTS REFERENCES C. Management of Hypothyroidism Chapter 48: Diagnosis of hypothyroidism INTRODUCTION CLINICAL DIAGNOSIS CLINICAL MANIFESTATIONS PREDISPOSITION TO HYPOTHYROIDISM CHRONIC AUTOIMMUNE THYROIDITIS AND HYPOTHYROIDISM LABORATORY TESTING SERUM THYROXINE DETERMINATIONS SERUM TSH DETERMINATIONS OTHER MEASURES OF THYROID HORMONE ACTION SCREENING, CASE FINDING, AND DIAGNOSIS DIAGNOSING THE CAUSE OF HYPOTHYROIDISM FUTURE ADVANCES IN LABORATORY ASSESSMENT REFERENCES Chapter 49: Treatment of hypothyroidism HISTORICAL PERSPECTIVE ON THE TREATMENT OF HYPOTHYROIDISM LEVOTHYROXINE THERAPY ENDPOINTS DURING LEVOTHYROXINE THERAPY FACTORS AFFECTING LEVOTHYROXINE DOSE INITIATION AND ADJUSTMENT OF LEVOTHYROXINE THERAPY CHOICE OF LEVOTHYROXINE PRODUCT LEVOTHYROXINE ABSORPTION, METABOLISM, AND TRANSPORT LEVOTHYROXINE THERAPY IN SPECIFIC SUBPOPULATIONS PATIENT SATISFACTION WITH LEVOTHYROXINE THERAPY LEVOTHYROXINE THERAPY AND T3 LEVELS THERAPIES OTHER THAN LEVOTHYROXINE THYROID EXTRACTS SYNTHETIC COMBINATION THERAPY LIOTHYRONINE THERAPY SUMMARY REFERENCES Chapter 50: Subclinical hypothyroidism INTRODUCTION ETIOLOGY AND NATURAL HISTORY CLINICAL AND BIOLOGIC IMPORTANCE CURRENT EVIDENCE TREATMENT CONSIDERATIONS TREATMENT RECOMMENDATIONS CONCLUSIONS REFERENCES Section V: Thyroid Diseases: Nontoxic Diffuse and Multinodular Goiter Chapter 51: Multinodular goiter: pathogenesis and management INTRODUCTION ETIOLOGY EPIDEMIOLOGY NATURAL HISTORY CLINICAL MANIFESTATIONS DIAGNOSIS EVALUATION MANAGEMENT IODINE SUPPLEMENTATION TSH SUPPRESSIVE THERAPY WITH LEVOTHYROXINE ANTITHYROID DRUGS SURGERY 131I THERAPY OTHER TREATMENT OPTIONS SUMMARY REFERENCES Chapter 52: Clinical evaluation and management of thyroid nodules CLINICAL EVALUATION LABORATORY EVALUATION SERUM HORMONE AND OTHER MEASUREMENTS IMAGING STUDIES ULTRASONOGRAPHY ELASTOGRAPHY RADIONUCLIDE THYROID SCINTIGRAPHY OTHER IMAGING STUDIES FINE-NEEDLE ASPIRATION BIOPSY RISK STRATIFICATION FOR THYROID NODULES TECHNIQUE OF FINE-NEEDLE BIOPSY RESULTS OF FINE-NEEDLE BIOPSY LIMITATIONS OF FINE-NEEDLE ASPIRATION BIOPSY OF THYROID NODULES CLINICAL RECOMMENDATIONS BASED UPON FNA CYTOLOGY RESULTS NONDIAGNOSTIC CYTOLOGY: BETHESDA I BENIGN CYTOLOGY: BETHESDA II ATYPIA OF UNDETERMINED SIGNIFICANCE/FOLLICULAR LESION OF UNDERMINED SIGNIFICANCE (AUS/FLUS) CYTOLOGY: BETHESDA III FOLLICULAR NEOPLASM CYTOLOGY (INCLUDES HüRTHLE CELL NEOPLASM): BETHESDA IV ROLE OF MOLECULAR TESTING FOR BETHESDA III AND IV NODULES SUSPICIOUS FOR MALIGNANCY CYTOLOGY: BETHESDA V MALIGNANT CYTOLOGY: BETHESDA VI TREATMENT AFTER THYROID SURGERY REFERENCES Section VI: Thyroid Cancers Chapter 53: Carcinomas of follicular epithelium: epidemiology and pathogenesis RADIATION EXTERNAL RADIATION AND THYROID CARCINOMA INTERNAL RADIATION AND THYROID CARCINOMA COMPARISON OF EXTERNAL AND INTERNAL RADIATION PREVENTING IODINE 131–RELATED THYROID CARCINOMA EVALUATION OF IRRADIATED PATIENTS RADIATION AND OTHER HEAD AND NECK TUMORS CLINICAL FEATURES OF RADIATION-RELATED THYROID NEOPLASMS GENETIC PREDISPOSITION SYNDROMIC NONMEDULLARY THYROID CARCINOMA NONSYNDROMIC FAMILIAL NONMEDULLARY THYROID CARCINOMA (FNMTC) GENETIC SUSCEPTIBILITY PRE-EXISTING THYROID DISEASE HORMONAL AND REPRODUCTIVE FACTORS DIETARY FACTORS IODINE AND GOITROGENS OTHER DIETARY FACTORS ANTHROPOMORPHIC AND METABOLIC FACTORS SMOKING AND OTHER ENVIRONMENTAL AGENTS SUMMARY REFERENCES Chapter 54: Genomic landscapes of thyroid cancers of follicular cell derivation GENOMIC HALLMARKS OF NEOPLASMS ARISING FROM THYROID FOLLICULAR CELLS FOLLICULAR NEOPLASMS AUTONOMOUSLY FUNCTIONING ADENOMA FOLLICULAR ADENOMA AND CARCINOMA PAPILLARY CARCINOMA NIFTP RARE PTC VARIANTS OTHER SOMATIC MUTATIONS TERT PROMOTER MUTATIONS SOMATIC COPY NUMBER ALTERATIONS HÜRTHLE CELL NEOPLASMS POORLY DIFFERENTIATED THYROID CANCER ANAPLASTIC THYROID CANCER GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL FACTORS DIAGNOSTIC IMPLICATIONS OF THYROID CANCER GENOMICS REFERENCES Chapter 55: Carcinoma of the follicular epithelium: surgical therapy INTRODUCTION THYROIDECTOMY NOMENCLATURE EXTENT OF THYROIDECTOMY AND RISK OF COMPLICATIONS SURGERY FOR INDETERMINATE THYROID NODULES THYROIDECTOMY FOR THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM CERVICAL LYMPH NODE DISSECTION NOMENCLATURE EXTENT OF LYMPH NODE DISSECTION AND RISK OF COMPLICATIONS LYMPHATIC DRAINAGE AND LOCATION OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM CLINICAL ASPECTS OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM PROGNOSIS OF NODAL METASTASIS IN THYROID CARCINOMA DERIVED FROM FOLLICULAR EPITHELIUM CENTRAL LYMPH NODE DISSECTION LATERAL LYMPH NODE DISSECTION SUMMARY REFERENCES Chapter 56: Staging and prognosis of differentiated thyroid cancer INTRODUCTION STAGING TO PREDICT RISK OF THYROID CANCER DEATH ELEMENTS AND COMPARISON OF PUBLISHED STAGING SYSTEMS EVOLUTION OF THE TNM SYSTEM TO THE CURRENT 8TH EDITION VALIDATION AND CONTROVERSIES IN 8TH EDITION TNM STAGING PREDICTING THE RISK OF THYROID CANCER RECURRENCE ELEMENTS OF INITIAL RISK STRATIFICATION SYSTEMS VALIDATION AND CONTROVERSIES FOR INITIAL RISK SYSTEMS DYNAMIC RISK STRATIFICATION/RESPONSE-TO-THERAPY ELEMENTS OF DYNAMIC RISK STRATIFICATION VALIDATION AND CONTROVERSIES FOR DYNAMIC RISK STRATIFICATION HOW TO USE CURRENT RISK STRATIFICATION SYSTEMS IN PRACTICE CONCLUSIONS REFERENCES Chapter 57: Medical management of differentiated epithelial cell thyroid cancer RADIOACTIVE IODINE THERAPY THE GOALS OF THE FIRST ADMINISTERED ACTIVITY OF RADIOACTIVE IODINE AFTER THYROIDECTOMY ABLATION OF RESIDUAL NORMAL THYROID TISSUE RAI TREATMENT AS AN ADJUVANT THERAPY PREPARATION FOR RAI THERAPY SELECTION OF RADIOACTIVE IODINE ACTIVITY FOR REMNANT ABLATION WHOLE-BODY 131I SCANS AND SPECT/CT RAI THERAPY FOR LOCAL OR DISTANT METASTATIC DISEASE INDICATIONS FOR RAI THERAPY TREATMENT OF PATIENTS WITH HIGH SERUM THYROGLOBULIN LEVELS AND NEGATIVE IMAGING STUDIES COMPLICATIONS OF RAI THERAPY FOLLOW-UP PARADIGMS EARLY FOLLOW-UP RECOMMENDATIONS (FIRST YEAR AFTER INITIAL THERAPY) FOLLOW-UP PARADIGMS BASED ON RESPONSE TO THERAPY RESTRATIFICATION ONGOING, DYNAMIC RISK ASSESSMENT DURING LONG-TERM FOLLOW-UP TSH-SUPPRESSIVE THYROID HORMONE THERAPY EXTERNAL BEAM RADIOTHERAPY SYSTEMIC THERAPY FOR ADVANCED DISEASE BIOLOGICALLY TARGETED THERAPIES CYTOTOXIC CHEMOTHERAPY OTHER PALLIATIVE INTERVENTIONS FOR SYMPTOMATIC METASTATIC DTC REFERENCES Chapter 58: Papillary microcarcinomas INCREASING INCIDENCE OF THYROID CANCER WITH STABLE MORTALITY SURGERY OF PAPILLARY MICROCARCINOMA AND OUTCOMES FREQUENT MULTIPLICITY AND REGIONAL LYMPH NODE METASTASIS PROGNOSIS OF HIGH-RISK AND LOW-RISK PAPILLARY MICROCARCINOMA SURGICAL APPROACH TO PMCs ACTIVE SURVEILLANCE OF LOW-RISK PAPILLARY MICROCARCINOMA HISTORY AND HYPOTHESIS PROTOCOL OF THE ACTIVE SURVEILLANCE AT KUMA HOSPITAL OUTCOMES OF ACTIVE SURVEILLANCE EVALUATION OF THE RISK OF TRACHEA AND RECURRENT LARYNGEAL NERVE INVASION INCIDENCES OF UNFAVORABLE EVENTS IN IMMEDIATE SURGERY VERSUS ACTIVE SURVEILLANCE MEDICAL ECONOMY OF MANAGEMENT OF PAPILLARY MICROCARCINOMA FACTORS THAT MIGHT BE ASSOCIATED WITH DISEASE PROGRESSION NATURAL HISTORY OF PAPILLARY CARCINOMA LIFETIME PROBABILITY OF DISEASE PROGRESSION TUMOR VOLUME KINETICS DURING ACTIVE SURVEILLANCE ESTIMATING TUMOR GROWTH BEFORE PRESENTATION IMPLEMENTING ACTIVE SURVEILLANCE REFERENCES Chapter 59: Medullary thyroid cancer NATURAL HISTORY TUMOR PROGRESSION PREOPERATIVE SCREENING SURGICAL TREATMENT DYNAMIC RISK STRATIFICATION AND FOLLOW-UP RECURRENT AND PERSISTENT DISEASE REOPERATION DISTANT DISEASE CONCLUSION REFERENCES Chapter 60: Poorly differentiated thyroid cancer, anaplastic thyroid cancer, and miscellaneous tumors of the thyroid POORLY DIFFERENTIATED THYROID CANCER DEFINITION/EPIDEMIOLOGY TREATMENT/PROGNOSIS ANAPLASTIC THYROID CANCER INTRODUCTION EPIDEMIOLOGY PATHOGENESIS CLINICAL PRESENTATION AND DIFFERENTIAL DIAGNOSIS PATHOLOGY GENOMICS/MOLECULAR PATHOLOGY/IMMUNOLOGY STAGING MANAGEMENT—GENERAL CONSIDERATIONS MANAGEMENT—STAGE IVA MANAGEMENT—STAGE IVB MANAGEMENT—STAGE IVC MANAGEMENT—OLIGOMETASTATIC STAGE IVC PALLIATIVE AND HOSPICE CARE ATC SUMMARY MISCELLANEOUS TUMORS OF THE THYROID GLAND HYALINIZING TRABECULAR TUMOR SQUAMOUS CELL CARCINOMA THYROID MUCOEPIDERMOID CARCINOMA SCLEROSING MUCOEPIDERMOID CARCINOMA WITH EOSINOPHILIA MUCINOUS CARCINOMA OF THE THYROID ECTOPIC THYMOMA SPINDLE EPITHELIAL TUMOR WITH THYMUS-LIKE DIFFERENTIATION INTRATHYROID THYMIC CARCINOMA PARAGANGLIOMA AND MESENCHYMAL/STROMAL TUMORS HEMATOLYMPHOID TUMORS GERM CELL TUMORS (BENIGN TERATOMA, IMMATURE TERATOMA, MALIGNANT TERATOMA) SECONDARY MALIGNANCIES OF THE THYROID ACKNOWLEDGMENTS REFERENCES Chapter 61: Thyroid cancer in children RISK OF THYROID CANCER IN THE PEDIATRIC PATIENT WITH A THYROID NODULE DIFFERENTIATED THYROID CANCERS PAPILLARY THYROID CARCINOMA (PTC) PAPILLARY THYROID MICROCARCINOMA (PTMC) FOLLICULAR VARIANT PTC FOLLICULAR THYROID CARCINOMA (FTC) MEDULLARY THYROID CARCINOMA MULTIPLE ENDOCRINE NEOPLASIA 2A MULTIPLE ENDOCRINE NEOPLASIA 2B EARLY THYROIDECTOMY IN MEN2 MANAGEMENT OF MTC IN MEN2 REFERENCES Section VII: The Thyroid in Infancy and Childhood Chapter 62: The maturation of thyroid function in the fetus, in the perinatal period and during childhood MATURATION OF THYROID FUNCTION IN UTERO ORGANOGENESIS AND STRUCTURAL DIFFERENTIATION OF THE THYROID GLAND FUNCTIONAL DIFFERENTIATION OF THE THYROID GLAND AND ONSET OF THYROID HORMONE SYNTHESIS THE ROLE OF THE PLACENTA FOR MATERNOFETAL INTERACTION MATURATION OF THE HYPOTHALAMIC–PITUITARY–THYROID AXIS SYNTHESIS OF THE THYROID HORMONE TRANSPORT PROTEINS REGULATION OF THYROID HORMONE LEVELS IN UTERO BY SULFATION REGULATION OF THYROID HORMONE LEVELS IN UTERO BY DEIODINATION ONTOGENY OF TRANSMEMBRANE THYROID HORMONE TRANSPORTERS ONTOGENY OF THYROID HORMONE RECEPTORS THE ROLE OF THYROID HORMONES FOR THE FETUS AND THE CHILD BRAIN DEVELOPMENT COCHLEA DEVELOPMENT RETINA DEVELOPMENT MUSCLE AND MYOCARDIAL DEVELOPMENT BONE DEVELOPMENT AND LINEAR GROWTH METABOLIC EFFECTS PERINATAL AND POSTNATAL CHANGES IN THYROID HORMONE SYNTHESIS AND METABOLISM PHYSIOLOGIC CHANGES IN THE TERM NEONATE THYROID FUNCTION IN THE PRETERM NEONATE THYROID FUNCTION IN SMALL FOR GESTATIONAL AGE NEONATES INFANTS, CHILDREN, AND ADOLESCENTS REFERENCES Chapter 63: Hypothyroidism in infants and children CONGENITAL HYPOTHYROIDISM NEWBORN SCREENING RATIONALE FOR BIOCHEMICAL SCREENING FOR CH PREMATURE AND VERY LOW–BIRTH-WEIGHT NEWBORNS NEWBORNS WITH TRISOMY 21 EVALUATION OF NEWBORNS WITH A POSITIVE SCREENING RESULT QUALITY ASSESSMENT OF SCREENING PROGRAMS CLASSIFICATION OF CH (Table 63-2) ETIOLOGY AND PATHOGENESIS PERMANENT CH TRANSIENT CH CLINICAL PRESENTATION DIAGNOSTIC EVALUATION (Table 63-3) TREATMENT AND OUTCOME ACQUIRED HYPOTHYROIDISM (CH) ETIOLOGIES (Table 63-4) CLINICAL PRESENTATION (Fig. 63-4) EVALUATION TREATMENT PROGNOSIS REFERENCES Chapter 64: Impaired sensitivity to thyroid hormone: defects of transport, metabolism, and action TH SECRETION, CELL-MEMBRANE TRANSPORT, METABOLISM, AND ACTION THE PARADOX OF COEXISTING MANIFESTATIONS OF THYROID HORMONE DEFICIENCY AND EXCESS THYROID HORMONE ACTION DEFECTS KNOWN AS RESISTANCE TO THYROID HORMONE RESISTANCE TO THYROID HORMONE BETA (RTHβ) CLINICAL CLASSIFICATION INCIDENCE AND INHERITANCE ETIOLOGY AND GENETICS MOLECULAR MECHANISMS OF TR ACTION PROPERTIES OF MUTANT TRβ RECEPTORS AND ASSOCIATED DOMINANT-NEGATIVE EFFECT MOLECULAR BASIS OF THE VARIABLE RTHβ PHENOTYPE RTHβ WITHOUT THRB GENE MUTATIONS (NON–TRβ-RTH) ANIMAL MODELS OF RTHβ PATHOGENESIS PATHOLOGY CLINICAL FEATURES COURSE OF THE DISEASE LABORATORY FINDINGS TH AND ITS METABOLITES THYROTROPIN AND OTHER THYROID STIMULATORS THYROID GLAND ACTIVITY AND INTEGRITY OF HORMONE SYNTHESIS IN VIVO EFFECTS OF TH IN VITRO TESTS OF THYROID HORMONE ACTION RESPONSES TO THE ADMINISTRATION OF THYROID HORMONE EFFECTS OF OTHER DRUGS DIFFERENTIAL DIAGNOSIS TREATMENT RESISTANCE TO THYROID HORMONE ALPHA (RTHα) BACKGROUND INCIDENCE AND INHERITANCE ETIOLOGY AND GENETICS MOLECULAR BASIS OF THE DEFECT AND PROPERTIES OF THE MUTANT TRα ANIMAL MODELS OF RTHα (SEE ALSO ANIMAL MODELS UNDER RTHβ, ABOVE) CLINICAL FEATURES LABORATORY FINDINGS DIFFERENTIAL DIAGNOSIS TREATMENT THYROID HORMONE CELL MEMBRANE TRANSPORTER DEFECT (THCMTD) CELL MEMBRANE TRANSPORTERS OF TH INHERITANCE AND INCIDENCE ETIOLOGY THE MCT8 GENE AND MUTATIONS CLINICAL FEATURES AND COURSE OF THE DISEASE LABORATORY FINDINGS SERUM TESTS OF THYROID FUNCTION OTHER SERUM TESTS X-RAYS AND IMAGING TESTS IN TISSUES GENETIC TESTING ANIMAL MODELS OF MCT8 DEFICIENCY MOLECULAR BASIS OF THE DISORDER DIFFERENTIAL DIAGNOSIS TREATMENT THYROID HORMONE METABOLISM DEFECT INTRACELLULAR METABOLISM OF TH ETIOLOGY AND GENETICS INCIDENCE AND INHERITANCE THE SBP2 GENE AND MUTATIONS CLINICAL FEATURES AND COURSE OF THE DISEASE LABORATORY FINDINGS MOLECULAR BASIS OF THE DISORDER THMD CAUSED BY MUTATION IN THE TRU-TCA1-1 GENE ANIMAL MODELS OF THMD DIFFERENTIAL DIAGNOSIS TREATMENT ACKNOWLEDGMENTS REFERENCES Chapter 65: Hyperthyroidism in the neonate, child, and adolescent CLINICAL EVALUATION OF THE HYPERTHYROID STATE BIOCHEMICAL EVALUATION OF THYROID FUNCTION GRAVES DISEASE ANTITHYROID DRUG THERAPY RADIOACTIVE IODINE THERAPY THYROIDECTOMY AND RISKS SOMATIC COMPLICATIONS OF GD NEONATAL THYROTOXICOSIS FETAL CONSIDERATIONS OTHER CAUSES OF HYPERTHYROIDISM HASHITOXICOSIS SUMMARY REFERENCES Section VIII: Thyroid Disorders in Pregnancy and Postpartum Chapter 66: Thyroid disorders during preconception, pregnancy, and the postpartum period PRECONCEPTION EPIDEMIOLOGY PHYSIOLOGY CLINICAL OUTCOMES AND MANAGEMENT PREGNANCY EPIDEMIOLOGY PHYSIOLOGY DIAGNOSIS OF THYROID DISEASE OVERT HYPOTHYROIDISM SUBCLINICAL HYPOTHYROIDISM ISOLATED HYPOTHYROXINEMIA AUTOIMMUNE THYROID DISEASE IN PREGNANCY HYPERTHYROIDISM POSTPARTUM POSTPARTUM THYROIDITIS REFERENCES Index