Pharmacotherapeutics of the Thyroid Gland by A.p. WeetmanPharmacotherapeutics of the Thyroid Gland by A.p. Weetman

Pharmacotherapeutics of the Thyroid Gland

byA.p. WeetmanEditorAshley Grossman

Paperback | January 19, 2012

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All the important pharmacological interactions affecting thyroid function are described in this book. The first section is devoted to the physiology and biochemistry of thyroid disease, putting the pharmacological interactions into perspective. The second section reviews all the important pharmacological effects on thyroid function and also deals with the impact of other environmental agents. The chapters are written by internationally recognised experts and extensively referenced to provide an up-to-date review of the pharmacological interactions important to the thyroid and its diseases.
Title:Pharmacotherapeutics of the Thyroid GlandFormat:PaperbackDimensions:370 pages, 23.5 × 15.5 × 0.02 inPublished:January 19, 2012Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642645194

ISBN - 13:9783642645198

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Table of Contents

1 Introduction: Clinical Aspects of Thyroid Treatment.- A. Introduction.- B. Choices of Treatment for the Hyperthyroidism of Graves' Disease.- I. Iodine-131 Therapy.- 1. Acceptability of Irradiation.- 2. Gastric Carcinoma.- 3. Ophthalmopathy.- 4. Calcitonin Deficiency.- II. Thyroid Surgery.- III. Antithyroid Drug Therapy.- C. Subclinical Hyperthyroidism.- D. Correct Dose of Thyroxine in Primary Hypothyroidism.- E. Subclinical Hypothyroidism: Treatment or Not?.- References.- 2 Control of TRH and TSH Secretion.- A. Introduction.- B. Negative Feedback Action of Thyroid Hormones.- C. Structure and Actions of TRH.- D. Structure and Actions of Somatostatin.- E. Actions of Neurotransmitters.- F. Actions of Cytokines and Inflammatory Mediators.- G. Physiological and Secondary TSH Changes.- References.- 3 The TSH Receptor.- A. Introduction.- B. TSH Receptor Cloning.- C. Structure of the TSHR in the Human Thyroid Gland.- D. Structure of the TSHR in Transfected Cells.- E. Controversies on Receptor Structure.- F. Expression of the TSH Receptor in the Baculovirus System.- G. Shedding of TSH Receptor Ectodomain in Thyroid and Transfected Cells.- H. Cellular Expression of the TSH Receptor.- I. Polarised Expression in the Thyroid.- II. Expression in Other Cell Types.- I. Intracellular Trafficking of the Receptor.- I. Polarized Expression in MDCK Cells.- II. Receptor Downregulation.- J. Structure-Function Relationships.- I. Transduction Pathways of the TSH Receptor.- II. Mutagenesis of Transmembrane and Intracellular Domains of the TSH Receptor.- III. Mutagenesis of the Extracellular Domain of the TSH Receptor.- K. Gene Structure and Regulation.- I. Gene Organisation.- II. Chromosomal Localisation and Genetic Mapping.- 1. Structure and Function of TSHR Promoter and 5' Flanking Region.- L. The TSH Receptor and Pathology.- I. Autoimmunity.- 1. The TSHR and the Genetics of Graves' Disease.- 2. Epitopes of the TSH Receptor Recognised by the Auto-antibodies.- II. Mutations of the TSH Receptor in Pathology.- 1. TSH Receptor and Tumorigenesis.- 2. TSHR and Non-immune Hyperthyroidism.- III. Constitutive Mutations and Model of Receptor Activation.- IV. Loss of Function Mutations.- 1. Animal Model.- 2. Thyroid Resistance to TSH Due to TSHR Mutations.- M. Conclusions.- References.- 4 Thyroid Hormone Synthesis, Plasma Membrane Transport and Metabolism.- A. Thyroid Hormone Synthesis.- I. Iodide Transport.- II. Biosynthesis of T4 and T3.- III. Thyroid Peroxidase.- IV. H2O2 Generation.- V. Iodination of Tyrosyl Residues in Thyroglobulin.- VI. Coupling of Iodotyrosines.- VII. Endocytosis of Iodinated Thyroglobulin.- VIII. Release of T3 and T4.- B. Thyroid Hormone Plasma Membrane Transport.- I. Studies of Plasma Membrane Thyroid Hormone Transport in Isolated Cells.- II. Liver Perfusion Studies.- III. (Patho)physiological Significance of Thyroid Hormone Plasma Membrane Transport: Its Role in the Generation of Low Serum T3 in Non-thyroidal Illness in Man.- C. Thyroid Hormone Metabolism.- D. Deiodination.- E. Characterization of Iodothyronine Deiodinases.- F. Sulphation.- I. Thyroid Hormone Sulphotransferases.- II. Deiodination of Iodothyronine Sulphates.- III. Occurrence of Iodothyronine Sulphates.- IV. Possible Role of Iodothyronine Sulphation.- G. Glucuronidation.- I. Thyroid Hormone UDP-Glucuronyltransferases.- II. Role of Thyroid Hormone Glucuronidation in Humans.- III. Glucuronidation of Iodothyroacetic Acid Analogues.- References.- 5 Thyroid Hormone Transport.- A. Introduction.- B. Serum Bingding in Humans.- I. Thyroxine-Binding Globulin.- 1. Normal Structure.- 2. Inherited Variants.- 3. Acquired Variants.- II. Transthyretin.- 1. Normal Structure.- 2. Inherited Variants.- III. Albumin.- 1. Normal Structure.- 2. Inherited Variants.- IV. Thyroxine Binding in Other Vertebrates.- V. Role of Binding Proteins.- C. Binding Kinetics.- I. Binding Kinetics, Capacity and Affinity.- II. Characterisation of High-Capacity, Low-Affinity Binding.- III. Specific Characterisation of TBG Binding.- IV. Assay of TBG.- D. Free Hormone Measurement.- I. Factors Influencing Validity.- 1. Radiochemical Purity.- 2. Protein-Tracer Interactions.- 3. Dilution Effects.- 4. Other Factors.- II. Non-isotopic Free T4 Methods.- III. Thyroid Hormone-Binding Ratio.- E. Interactions with Competitors.- I. Pre-dilution and Co-dilution.- II. Estimation of In Vivo Competitor Potency.- III. In Vivo Kinetics of Competitors.- IV. Interaction Between Competitors.- V. Spurious Competition.- VI. Drug Competition at Other Sites.- References.- 6 Molecular Biology of Thyroid Hormone Action.- A. Introduction.- B. Extranuclear Mechanisms of Thyroid Hormone Action.- I. Plasma Membrane and Intracellular Transport of Thyroid Hormones.- II. Extranuclear Sites of Thyroid Hormone Action.- C. Identification of High-Affinity Nuclear-Binding Sites for Thyroid Hormones.- D. Cloning of cDNAs Encoding Nuclear Receptors for T3.- E. Recognition of Two Genes Encoding Two Major Classes of TR.- F. Thyroid Hormone Response Elements.- G. Structural Characteristics of TRs and Identification of Functional Domains.- I. DNA-Binding Domain.- II. Hormone-Binding Domain.- III. Nuclear Localisation.- IV. Dimerisation.- V. Silencing of Basal Gene Transcription by Unliganded TR.- VI. Transcription Activation.- 1. Hormone-Dependent Activation of Transcription (AF-2).- 2. Constitutive Transcription Activation (AF-1).- H. Role of the TR Splice Variant TR?2.- I. TRs and Human Disease.- References.- 7 Iodine: Metabolism and Pharmacology.- A. Introduction.- B. Iodide Transport and Organification.- C. Thyroid Autoregulation.- I. Autoregulation in Animals.- 1. Wolff-Chaikoff Effect and Escape.- 2. Effects of Graded Doses of Iodide.- II. Autoregulation in Humans.- 1. Effects of Moderate Doses of Iodide.- 2. Effects of Excess Iodide in Normal Subjects.- III. Intracellular Effects of Excess Iodide in Relation to Other Regulators.- 1. Signal Transduction.- 2. Expression of HLA Molecules and Other Thyroidal Proteins.- 3. Protein Synthesis.- 4. Organic Iodinated Lipids.- 5. Growth Factors.- IV. Mechanism of Autoregulation.- 1. Acute Inhibitory Effect (Wolff-Chaikoff Effect).- 2. Mechanism of Adaptation.- 3. Species Differences in Autoregulation.- 4. Role of TSH in Autoregulation.- References.- 8 Antithyroid Drugs: Their Mechanism of Action and Clinical Use.- A. Introduction.- B. Hyperthyroidism.- C. Pharmacokinetics.- D. Mechanism of Action.- I. Inhibition of TPO.- 1. Thyroid Hormone Synthesis.- 2. Drug Action.- II. Immunological Effects.- 1. Graves' Disease.- 2. Drug Action.- E. Clinical Use.- I. Indications.- II. Adverse Effects.- III. Administration and Use.- 1. Graves' Disease.- 2. Drug Usage with Radioiodine.- 3. Drug Usage in Pregnancy.- 4. Thyroid Storm.- F. Conclusions.- References.- 9 Effect of Lithium on the Thyroid Gland.- A. Introduction.- B. Effect on Thyroid Physiology.- I. Iodine Concentration.- II. Intrathyroidal Effects.- III. Effect on Thyroid Hormone Secretion.- IV. Effect on Peripheral Thyroid Hormone Metabolism.- C. Effect on the Hypothalamic-Pituitary Axis.- D. Lithium and Cell Function.- E Immunological Effects on Thyroid Function.- F. Effect on Thyroid Hormone Action.- G. Clinical Effects on the Thyroid.- I. Goitre.- II. Hypothyroidism.- III. Hyperthyroidism.- H. Clinical Use in Thyroid Disease.- References.- 10 Amiodarone and the Thyroid.- A. Pharmacology of Amiodarone.- I. Physicochemical Properties.- II. Pharmacokinetics.- 1. Absorption and Bioavailability.- 2. Plasma Kinetics.- 3. Tissue Distribution.- 4. Metabolism.- 5. Elimination.- III. Pharmacology.- 1. Electrophysiological Effects.- 2. Haemodynamic Effects.- IV. Pharmacotherapy.- 1. Indications for Use.- 2. Dosing Schedules.- V. Toxicology.- 1. Nature of Side Effects.- 2. Pathogenesis of Side Effects.- 3. Prevention of Side Effects.- B. Effects of Amiodarone on Thyroid Hormone Secretion and Metabolism.- I. Changes in Plasma Thyroid Hormone Concentrations.- 1. Human Studies.- 2. Animal Studies.- II. Changes in Thyroid and Extrathyroidal Tissues.- 1. Peripheral Tissues.- 2. Thyroid.- 3. Pituitary.- III. Changes in Thyroid Hormone Kinetics.- 1. Human Studies.- 2. Animal Studies.- IV. Summary.- C. Amiodarone-Induced Thyrotoxicosis and Amiodarone-Induced Hypothyroidism.- I. Diagnosis.- II. Incidence.- III. Pathogenesis.- 1. Amiodarone-Induced Hypothyroidism.- 2. Amiodarone-Induced Thyrotoxicosis.- IV. Treatment.- 1. Amiodarone-Induced Hypothyroidism.- 2. Amiodarone-Induced Thyrotoxicosis.- 3. Amiodarone Treatment in Pregnancy.- 4. Amiodarone Treatment of Hyperthyroidism.- V. Summary.- D. Amiodarone as a Thyroid Hormone Antagonist.- I. Hypothyroid-Like Effects of Amiodarone.- 1. Heart.- 2. Liver.- 3. Pituitary.- II. Amiodarone as a T3 Receptor Antagonist.- 1 Inhibition of T3 Binding to Nuclear T3 Receptors.- 2. Structure-Function Relationship.- III. Summary.- References.- 11 Effects of Other Pharmacological Agents on Thyroid Function.- A. Introduction.- B. Effects of Various Drugs on Thyroidal Hormonogenesis.- C. Effects of Drugs on Thyroid Hormone Metabolism.- I. Deiodination.- II. Microsomal Oxidation.- D. Drug Effects on Cellular and Intestinal Uptake of Thyroid Hormone.- I. Cellular Uptake.- II. Intestinal Absorption.- References.- 12 Effects of Environmental Agents on Thyroid Function.- A. Introduction.- B. Chemical Categories, Sources, Pharmacokinetics, and Mechanism of Action.- I. Sulphurated Organics.- 1. Thiocyanate, Isothiocyanates, and Thio-oxazolidone (Goitrin).- 2. Disulphides.- II. Flavonoids.- III. Polyhydroxyphenols and Phenol Derivatives.- IV. Pyridines.- V. Phthalate Esters and Metabolites.- VI. Polychlorinated and Polybrominated Biphenyls.- VII. Other Organochlorines.- VIII. Polycyclic Aromatic Hydrocarbons.- References.- 13 Thyroid Hormone Antagonism.- A. Introduction.- B Inhibition of Uptake.- I. Mechanisms of Cell Entry.- II. Purification of Membrane-Binding Sites.- III. Inhibition of Uptake.- IV. Uptake Inhibition and Hormone Responsiveness.- C. Cytoplasmic Binding.- I. Role of Cytoplasmic Binding.- II. Cytoplasmic Binding and Hormone Responsiveness.- III. Pharmacological Antagonism of Cytoplasmic Binding.- D. Antagonism at the Receptor Level.- I. Thyroid Hormone Receptors and the Receptor Superfamily.- II. Heterogeneity Among Thyroid Hormone Receptors.- III. Tissue Distribution of Receptors.- IV. Receptor Regulation of Tissue Responsiveness.- V. Drug Interactions at the Ligand-Binding Site.- References.- 14 Immunomodulatory Agents in Autoimmune Thyroid Disease.- A. Introduction.- B. Hormones and Autoimmune Thyroid Disease.- I. Sex Hormones.- II. Glucocorticoids.- III. Thyroid Hormones.- C. Toxins and Autoimmune Thyroid Disease.- D. Trace Elements and Autoimmune Thyroiditis.- E. Drugs and Autoimmune Thyroid Disease.- F. Cytokines and Autoimmune Thyroid Disease.- G. Immunomodulatory Agents in TAO.- I. Glucocorticoids.- II. Other Immunosuppressive Drugs.- III. Other Treatments.- References.