Table of Contents
Preface
Acknowledgments
Editors
Contents
Contributors
Part I: Fundamental Concepts
1: Thyroid: A General Overview
Introduction
Thyroid Gland: Basic Structure
Thyroid Dysfunction: Distribution and Burden
Classification of Thyroid Dysfunction
Thyroid Dysfunction and Health Issues
Screening for Thyroid Disorders
Accuracy of Screening Tests
The USPSTF: Summary of Recommendation
Recommendations of Other Authorities
Conclusion
References
2: Functions of Thyroid Hormones
Introduction
Thyroid Hormone Synthesis
Steps Involved in Synthesis of Thyroid Hormones
Role of Iodine in Thyroid Hormone Synthesis and Function
Wolff- Chiakoff Effect
Central Regulation of Thyroid Hormone Synthesis: The ‘Hypothalamic –Pituitary- Thyroid Axis’
Production of TRH
Hypophysiotropic and Non-hypophysiotropic Neurons
Role of Autonomic Nervous System in Regulation of Thyroid Function
Inactivation of Secreted TRH
Negative Feedback Regulation of Hypophysiotropic TRH Neurons
Deiodinases and Their Role in Negative Feedback Regulation
Role of Thyroid Hormone Transporters in Secretion of Ths
Thyroid Hormones- Mechanism of Action
Genomic Pathways
Non-genomic Pathways
Thyroid Hormone Functions
Role in Brain Development
Effect on Myocardium
Effect on Bone
Effect on Adipose Tissue
Effect on Liver
Effect on Pituitary
Effect on Fetal Growth and Maturation
Effect on Growth
Effect on Fetal Metabolism (Oxygen (O2) Consumption)
Effect on Fetal Tissue Maturation
Effect on Lung Maturation
Effect on Fetal Heart and Cardiovascular System
Other Important Effects
Conclusion
References
3: Iodine and the Thyroid
Introduction
Epidemiology
Definition of IDD and Its Impact on Health and on the Population
Iodine Chemistry
Iodine Ecology and Cycle
Food Sources of Iodine
Iodine Metabolism
Toxic Effects of Iodine Excess
Diagnosis of Iodine Deficiency
IDD Prevention and Treatment
Impact of Iodine Supplementation in Deficient Populations
Conclusion
References
4: The Role of Thyroid Hormones in Neural Development
Introduction
Thyroid Hormone Synthesis and Secretion
Thyroid Hormone Transport, Uptake and Metabolism
Disruption of Brain Development by Thyroid Hormone Depletion
Effects of Thyroid Hormones on Neural Cell Proliferation and Differentiation
Non-genomic and Mitochondrial Effects of Thyroid Hormones
Conclusion
References
5: Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): Etiopathogenesis, Clinical Manifestations and Diagnosis
Introduction
Background and History
Epidemiology
Genetics and Etiopathogenesis
Clinical Manifestations
Clinical Diagnosis
Laboratory Diagnosis
Imaging Diagnosis
Histopathological Diagnosis
Conclusions
Bibliography
Part II: Thyroid Dysfunction and Clinical Application
6: Thyroiditis
Introduction
Thyroiditis Without Thyroid Pain and Tenderness
Hashimoto’s Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Painless Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Postpartum Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Amiodarone-Associated Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Thyroiditis Induced by Other Drugs
Lithium
Epidemiology
Etiology and Pathogenesis
Clinical Features, Diagnostic Evaluation and Differential Diagnosis
Treatment
Interferon-alpha
Epidemiology
Etiology and Pathogenesis
Clinical Features, Diagnostic Evaluation and Differential Diagnosis
Treatment
Interleukin-2
Epidemiology
Etiology and Pathogenesis
Clinical Features, Diagnostic Evaluation and Differential Diagnosis
Treatment
Tyrosine Kinase Inhibitors
Epidemiology
Etiology and Pathogenesis
Clinical Features, Diagnostic Evaluation, Differential Diagnosis
Treatment
Riedel’s Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Infiltrative Thyroid Disorders
Thyroiditis with Thyroid Pain and Tenderness
Subacute Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Suppurative Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Radiation-Induced Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Palpation or Trauma-Induced Thyroiditis
Epidemiology
Etiology and Pathogenesis
Clinical Features
Diagnostic Evaluation
Differential Diagnosis
Treatment
Conclusion
References
7: Hypothyroidism
Introduction
Historical
Definitions
Epidemiology
Etiology
Primary Hypothyroidism
Hashimoto’s Thyroiditis
Iodine Deficiency
Iodine Excess
Iatrogenic
Drugs
Thyroid Infiltration and Infections
Transient Hypothyroidism
Primary Congenital Hypothyroidism
Central Hypothyroidism
Acquired Pituitary and Hypothalamic Disorders
Central Congenital Hypothyroidism
Drugs
Other Disorders
Resistance to Thyroid Hormone
Consumptive Hypothyroidism
Clinical Features
Skin and Appendages
Cardiovascular
Respiratory
Gastrointestinal
Neurologic
Musculoskeletal
Renal
Hematopoietic
Endocrine
Reproductive
Energy Metabolism
Course of the Disease
Primary Hypothyroidism
Central Hypothyroidism
Hypothyroidism in Infants and Children
Screening
Congenital Hypothyroidism
Acquired Hypothyroidism
Diagnosis
Differential Diagnosis
Primary Hypothyroidism
Central Hypothyroidism
Treatment
Primary Overt Hypothyroidism
L-T4 Monotherapy
Combination T4 and T3 Therapy
L-T3 Monotherapy
Desiccated Thyroid
Compounded Thyroid Hormones
Dietary Supplements, Nutraceuticals and Other Over-the-Counter Products
Central Hypothyroidism
Congenital Hypothyroidism
Conclusion
References
8: Hyperthyroidism
Introduction
Etiology
Graves Disease
Epidemiology
Pathophysiology and Genetic Interplay
Other Associated Autoimmune Diseases
Graves Ophthalmopathy
Other Causes of Hyperthyroidism
Toxic Multinodular Goiter (Plummer Disease)
Toxic Adenoma
Thyroiditis
Drug-Induced Hyperthyroidism
Tumors Induced Hyperthyroidism
TSH-Secreting Pituitary Adenoma
Hyperthyroidism Secondary to Thyroid Hormone Resistance
Hyperthyroidism due to TSH-Receptor Mutations
Clinical Features
Features Related to Other Causes of Hyperthyroidism
Apathetic Hyperthyroidism
Diagnostic Modalities
Hormonal Assays
Antibodies
Other Relevant Investigations
Ultrasound
Radioisotope Thyroid Scan
Radioisotope Findings
MRI/CT Scan
Treatment
Symptomatic Relief
Diet and Activity
Antithyroid Medications
Adverse Effects of Thioamide Antithyroid Medications
Radioactive Iodine 131 Ablation (RAI131)
Other Less Commonly Used Antithyroid Medications
Thyroidectomy
Indications for Thyroidectomy
Preparation for Thyroidectomy
Adverse Effects of Thyroidectomy
Postoperative Bleeding
Infection
Injury to the Recurrent Laryngeal Nerve
Injury to the Superior Laryngeal Nerve
Hypoparathyroidism
Hypothyroidism
Thyrotoxic Storm
Follow up After Thyroid Surgery
Cause-Specific Treatment
Future Directions
Conclusion
References
9: Autoimmune Thyroid Disease (Flajani-Parry-Graves-von Basedow Disease): An Overview of Treatment
Introduction
Anti-thyroid Medications
Doses and Follow-up Regimes
Adverse Reactions
Radioactive Iodine Treatment
I-131 Adverse Effects and Risk of Malignancy
Surgical Treatment for GD
Special Conditions
Pregnancy
Graves’ Eye Disease
Pretibial Myxedema
Conclusions
Bibliography
10: Subclinical Hyperthyroidism
Introduction
Causes
Exogenous Subclinical Hyperthyroidism
Endogenous Subclinical Hyperthyroidism
Epidemiology and Natural History
Clinical Findings
Cardiovascular Mortality Risk
Atrial Fibrillation
Coronary Heart Disease, Heart Failure, and Other Cardiac Factors
Cardiovascular Mortality
Bone and Mineral Metabolism
Dementia Cognitive Function
Quality of Life
Evaluation
Diagnosis
Pregnancy
Screening Guidelines
Management
Patients on T4 for the Treatment of Hypothyroidism
Patients on Suppressive Levothyroxine Therapy
Endogenous Subclinical Hyperthyroidism
Patients at High Risk for Complications
Patients at Low Risk for Complications
Treatment Options
Conclusion
References
11: Subclinical Hypothyroidism
Introduction
Epidemiology
Etiology
Screening for Subclinical Hypothyroidism
Diagnosis
What Is the Upper Limit of Normal for the Serum TSH Level?
Differential Diagnosis
Evaluation
Consequences of Subclinical Hypothyroidism
Systemic Symptoms of Hypothyroidism
Progression to Overt Hypothyroidism
Cardiovascular Disease
Cardiovascular Mortality
Non-alcoholic Fatty Liver Disease
Neuropsychiatric Symptoms
Neuromuscular Dysfunction
Potential Consequences
Pregnancy
Effects of Thyroid Hormone Replacement
Hypothyroid Signs and Symptoms
Cardiovascular Disease
Serum Lipid and Apoprotein Concentrations
Other Benefits
Management of Subclinical Hypothyroidism
Serum TSH Concentration of 3–5 mlu/l
Serum TSH Concentration of 5.1–10 mlu/l
Serum TSH Concentration Greater Than 10 mlu/l
Candidates for T4 Replacement
Thyroid Peroxidase Antibodies
Arguments for Treatment
Arguments Against Treatment
Goals of Treatment
Dose Modification Strategy
Conclusion
References
12: Thyroid Emergencies
True Thyroid Emergencies
Thyroid Storm
Pathophysiology
Signs/Symptoms
Establishing Diagnosis
Scoring System
Treatment
Do and Don’ts/Things Not to Be Missed
Follow Up of Patients
Myxedema Coma
Pathophysiology
Establishing Diagnosis
Signs/Symptoms
Treatment
Do and Don’t/What Not to Miss
Follow Up of Patients
Thyroid Dysfunction Requiring Urgent Measures
Thyroid Dysfunction During Pregnancy
Hyperthyroidism
Hypothyroidism
Neurological Presentation of Thyroid Disease
Cognitive Disorders and Seizures
Neuromuscular Emergencies
Cardiovascular Emergencies
Medication Exposure and Thyroid Emergencies
Acute Iodine Exposure: Jod-Basedow Phenomenon/Wolff-Chaikoff Effect
Lithium Intoxication
Amiodarone-Induced Thyroid Emergencies
Post RAI
Thyroxine Overdose
Conclusion
References
13: Thyroid Nodule
Introduction
Epidemiology
Clinical Problem
Clinical Evaluation
History
Physical Examination
High Suspicion for Malignancy
Moderate Suspicion for Malignancy
Investigations
Indications for Evaluation [22]
Biochemical Tests
Serum TSH
Serum Thyroglobulin
Serum Calcitonin
Imaging
Radionuclide Scanning
Thyroid Ultrasound
Other Imaging Studies
Fine Needle Aspiration
Treatment
Overview of Treatment Options for Solitary Thyroid Nodules
Surgery
Radio-Iodine
Percutaneous Ethanol Injection
Levothyroxine
Conclusion
References
14: Thyroid Cancer
Introduction
Calcification
Differentiated Thyroid Cancers
Papillary Cell Carcinoma
Epidemiology
Pathology
Follicular Thyroid Carcinoma
Epidemiology
Pathology
Molecular Biology of Differentiated Thyroid Cancer
Diagnosis
Investigations
Treatment of Differentiated Thyroid Cancer
Surgery
Radioactive Iodine (RAI)
TSH Suppression Therapy
Long Term Management
Treatment Options for Advanced DTC
Novel Therapies
Medullary Thyroid Cancer
Epidemiology and Pathology
Presentation and Diagnosis
Treatment
Anaplastic Thyroid Carcinoma
Melignant Thyroid Lymphoma
Conclusion
References
15: Thyroid Dysfunction and Mental Disorders
Introduction
Basic Concepts and Terminology
Neurophysiology of Psychiatric Disorders
Mood Disorders
Antidepressant Effects on Thyroid Function
Psychosis
Cognitive Changes
Anxiety Disorders
Mechanism of Psychiatric Disorders Associated with Thyroid Dysfunction
Psychiatric Management
Outcome of Mental Disturbances
Conclusion
References
16: Thyroid Dysfunction and Arrhythmias
Introduction
Genomic Action of Thyroid Hormone on Heart
Non Genomic Action of Thyroid Hormone on Heart
Electrophysiology and Mechanism of Action of T3 on the Atria
Electrophysiology and Mechanism of Action of T3 on the Ventricles
Relation Between Thyroid Hormone and Adrenergic System
Mechanism Underlying the Effect of Thyroid Hormone (TH) on the Arrhythmogenesis
Effects of Thyroid Hormones Excess on the Atrias
Effects of Thyroid Hormones Excess on the Ventricles
Supraventricular Arrhythmia
Atrial Arrhythmia
Hyperthyroidism
Subclinical Hyperthyroidism and Atrial Fibrillation
Hypothyroidism and Subclinical Hypothyroidism
Euthyroid Range in Older Adults
Should We Anticoagulate and Attempt Cardioversion in Those with AF?
Arrhythmia and Amiodarone-Induced Hyperthyroidism
Other Supraventricular Arrhythmia
Ventricular Arrhythmia
Hyperthyroidism
Subclinical Hyperthyroidism
Hypothyroidism
Subclinical Hypothyroidism
Conclusion
References
Part III: Pregnancy and Thyroid Dysfunction
17: Pregnancy and Hypothyroidism
Introduction
Physiologic Changes in Thyroid Function During Pregnancy
Thyroid Function and the Fetus
Subclinical Hypothyroidism During Pregnancy
Thyroid Autoimmunity and Subclinical Hypothyroidism
Hypothyroidism in Pregnancy
Feto-maternal Risk
Screening
Diagnosis
Indications for Thyroid Testing in Pregnancy [28]
Treatment
Thyroxine Replacement
Iodine Replacement
Monitoring Thyroid Status During Pregnancy
Prognosis
Preconception Counseling
Conclusion
References
18: Pregnancy and Hyperthyroidism
Introduction
Clinical Features of Hyperthyroidism During Pregnancy
Impact of Hyperthyroidism During Pregnancy
Diagnosis of Hyperthyroidism During Pregnancy
Establishing the Cause of Hyperthyroidism During Pregnancy
Gestational Transient Thyrotoxicosis
Graves’ Disease
Pre-pregnancy Counseling
Radioactive Iodine Ablation or Surgery
Antithyroid Drugs [4, 6, 29]
Incidence of Hyperthyroidism During Pregnancy
Treating Graves’ Disease in Pregnancy
Monitoring a Pregnant Woman on ATDs (Table 18.5)
Natural Course of Graves’ Disease During Pregnancy
Thyroidectomy for Graves’ Disease During Pregnancy
Metarnal TRAb and Its Impact on the Fetus
Fetal and Neonatal Hyperthyroidism
Fetal Monitoring in a Woman with Graves’s Disease
ATDs Use in Lactation
Graves’ Disease in Post-partum Period
Conclusion
References
Index
