Thyroid Disease in Adults (eBook)

Foreword 4
Contents 5
Presentation of Contributors 13
List of Abbreviations and Definitions 14
1 Historical Background 20
1.1 Goitre and Iodine 20
1.2 Hypothyroidism 20
1.3 Hyperthyroidism 22
2 Anatomy and Physiology 24
2.1 The Embryologic Development and Anatomy of the Thyroid Gland 24
2.1.1 Embryology 24
2.1.2 Anatomy 24
2.1.3 Blood Supply 26
2.1.4 Lymph Drainage 27
2.1.5 Nerves 28
2.2 Iodine and the Thyroid 28
2.2.1 Transport of Iodine 28
2.2.2 The Iodine Pool 30
2.3 TSH and TSH Receptors 30
2.4 Synthesis and Secretion of Thyroid Hormones 31
2.4.1 Thyroglobulin 34
2.4.2 Regulation of Iodine Metabolism 35
2.4.3 Selenium 35
2.5 Hypothalamus–Pituitary–Thyroid Axis 36
2.6 Deiodinases 37
2.7 Mechanisms of Action of Thyroid Hormones 37
2.8 Biochemical Indicators of the Peripheral Effects of Thyroid Hormones 41
2.9 Factors Affecting Thyroid Hormone Homeostasis 43
2.9.1 Circadian and Seasonal Variation 43
2.9.2 Variation with Age 43
2.9.3 Effects of Stress and the Environment 43
2.10 Effects of General Illness and Pharmaceuticals (NTI) 44
3 Biochemical Investigations 47
3.1 TSH 47
3.2 TRH-Stimulated TSH Secretion 50
3.3 Thyroid Hormones 50
3.4 Free Thyroid Hormones 51
3.5 Analytical Problems 52
3.6 Reference Ranges (Normal Values) for Thyroid-Associated Hormone Analyses 53
3.7 Antibodies Against Thyroperoxidase (TPOAb) 54
3.8 Antibodies Against the TSH Receptor (TRAb) 55
3.9 Thyroglobulin (Tg) 56
3.10 Antibodies Against Thyroglobulin (TgAb) 56
3.11 Thyroxine-Binding Globulin (TBG) and Transthyretin (Prealbumin) 57
3.12 Calcitonin 57
3.13 Iodine in Urine 57
3.14 Genetic Diagnostics 57
3.15 Analytical Strategy 58
3.15.1 Hypothyroidism 58
3.15.2 Thyrotoxicosis 59
4 Other Investigations 64
4.1 Investigations Using Radionuclides 64
4.1.1 Gamma Camera Investigations (Scintigraphy) 65
4.1.2 Radioiodine Uptake Investigation (Radioiodine Uptake Test) 66
4.1.3 Uptake of Radioiodine by the Thyroid in Various Clinical Conditions 67
4.1.4 Perchlorate Test 69
4.1.5 Important Features of Radionuclide Investigations 69
4.2 Positron Emission Tomography (PET) 71
4.3 X-ray, CT, and MR 71
4.4 Ultrasound 72
4.5 Fine-Needle Biopsy 75
4.5.1 Sampling Technique 75
4.5.2 Cytological Findings 76
4.5.3 Complications 77
4.5.4 Histological and Cytological Diagnostics 77
5 Clinical Investigation of the Thyroid 83
5.1 Medical History 83
5.2 Physical Examination 83
6 Iodine and the Thyroid Gland in Health and Sickness 87
6.1 Global Aspects of Iodine Intake 88
6.2 Thyroid Dysfunction Caused by Excessive Iodine Intake 89
6.3 Iodine in Foodstuffs and Medical Preparations 90
6.4 Iodine Blocking 91
6.4.1 Nuclear Accidents 91
6.4.2 Radionuclide Investigations and Treatments 92
7 Autoimmunity and the Thyroid Gland 94
7.1 Immunological Background 94
7.1.1 Antigen-Presenting Cells 94
7.1.2 MHC Molecules 95
7.1.3 T and B Lymphocytes 95
7.1.4 Interaction Between T Cells and APC (Simplified Model) 95
7.1.5 Cytolytic T Lymphocyte-Associated Antigen 4 (CTLA-4) 97
7.1.6 Fas/Fas-L and the Destruction of Cells 97
7.2 Autoimmunity 98
7.2.1 Hashimoto or Graves’ Disease? 98
7.2.2 Antithyroid Drugs and the Immunological Process 99
7.3 Predisposing Factors 99
7.3.1 Genetic Predisposition 99
7.3.2 Other Endogenous Causes 101
7.4 Exogenous Factors 101
7.4.1 Iodine 101
7.4.2 Smoking 101
7.4.3 Stress 101
7.4.4 Infections/Cytokines 102
7.5 Autoimmune Polyglandular Syndrome 102
7.6 Immunological Markers in Clinical Work 102
7.6.1 TPO Antibodies 102
7.6.2 TSH Receptor Antibodies 103
7.6.3 Clinical Applications 103
7.7 Treatment Strategy 104
7.7.1 Autoimmune Thyroiditis 104
7.7.2 Graves’ Disease 104
7.7.3 Pregnancy 105
8 Growth Regulation of the Thyroid Gland 106
8.1 TSH 107
8.2 Hyperplasia and Goitre 107
8.3 Neoplasms and Tumours 108
9 Thyroiditis and Pathogenesis 111
9.1 Thyroiditis 111
9.2 Autoimmune Thyroiditis 112
9.2.1 Hashimoto’s Disease 112
9.2.2 Atrophic Autoimmune Thyroiditis 115
9.2.3 Silent Thyroiditis and Postpartum Thyroiditis 115
9.2.4 Juvenile Thyroiditis 116
9.2.5 Focal Thyroiditis 117
9.2.6 Steroid-Sensitive Encephalopathy Associated with Autoimmune Thyroiditis 117
9.3 Other Triggering Factors for Thyroiditis 118
9.3.1 Subacute Thyroiditis (de Quervain’s Disease) 118
9.3.2 Iatrogenic Thyroiditis 118
9.3.3 Radiation-Induced Thyroiditis 118
9.3.4 Trauma-Induced Thyroiditis 118
9.3.5 Riedel Thyroiditis 119
9.3.6 Acute Bacterial Thyroiditis 119
10 Causes of Hypothyroidism 121
10.1 Primary Hypothyroidism and Chronic Autoimmune Thyroiditis 121
10.2 Epidemiology 121
10.3 Hypothyroidism After Treatment for Hyperthyroidism 122
10.4 Hypothyroidism After Surgery for Nontoxic Multinodular Goitre 122
10.5 Hypothyroidism After Surgery for Thyroid Cancer 123
10.6 Central Hypothyroidism 123
10.7 Iodine-Induced Hypothyroidism 123
10.8 Iatrogenic (Medicine-Induced) Hypothyroidism 123
10.9 Hypothyroidism After External Radiation of the Head and Neck Regions 124
10.10 Other Causes of Hypothyroidism 124
11 Symptoms of Hypothyroidism 125
11.1 Autoimmune Thyroiditis – Natural Progression 125
11.2 Organ-Related Symptoms 127
11.3 Symptoms and Findings in Hypothyroidism 128
11.3.1 Neurological 128
11.3.2 Mental 128
11.3.3 Gastrointestinal 128
11.3.4 Musculoskeletal 129
11.3.5 Dermatological 129
11.3.6 Ear, Nose and Throat 129
11.3.7 Gynecological and Andrological 129
11.3.8 Heart and Blood Vessels 129
11.3.9 Hematological 129
11.3.10 Respiratory 130
11.3.11 Renal and Urological 130
11.3.12 Electrolyte Balance, Intermediary Metabolism 130
11.3.13 Changes in Lipid Metabolism 130
11.4 Central Hypothyroidism 130
12 Treatment of Hypothyroidism 132
12.1 Primary Hypothyroidism 132
12.2 Laboratory Tests – Special Aspects 134
12.3 Special Problems 134
12.4 Resorption of Thyroxine 135
12.5 Pharmaceutical Interaction in Thyroxine Treatment 135
12.6 Oestrogens and Hypothyroidism 135
12.7 Do All Patients Tolerate Thyroxine? 136
12.8 Treatment with Triiodothyronine 136
12.9 Parenteral Treatment with Thyroid Hormone 137
12.10 Overdosing with Thyroxine and Triiodothyronine 138
12.11 Compliance 138
12.12 Temporary Treatment with Thyroxine 138
12.13 Central (Secondary) Hypothyroidism 139
13 Subclinical Hypothyroidism 140
13.1 Introduction 140
13.2 Prevalence 140
13.3 Substitution Treatment with Thyroxine in Subclinical Hypothyroidism 141
14 Myxoedema Coma 143
14.1 Symptoms 143
14.2 Diagnostic Tests 144
14.3 Treatment 144
14.3.1 Thyroid Hormone 144
14.3.2 Hydrocortisone 144
14.3.3 Monitoring Respiration 145
14.3.4 Monitoring Circulation 145
14.3.5 Temperature Regulation 145
14.3.6 Fluids and Electrolyte Treatment 145
14.3.7 Infection 145
14.3.8 Coagulation 145
14.3.9 Miscellaneous 145
15 Causes of Thyrotoxicosis – an Overview 147
16 Symptoms of Thyrotoxicosis 150
16.1 Weight Loss and Energy Metabolism 150
16.2 Mental Problems 150
16.3 Muscle Weakness 151
16.4 Cardiac Arrhythmia and Cardiac Insufficiency 151
16.5 Sympathetic Nervous System 152
16.6 Dermatological Symptoms 153
16.7 Reduced Glucose Tolerance and Effects on Blood Lipids 153
16.8 Fertility 153
16.9 Bones and Calcium 153
17 Hyperthyroidism Treatment Options – an Overview 155
17.1 General Considerations 155
17.2 Medical Treatment 156
17.2.1 Antithyroid Drugs 156
17.2.2 Treatment with Stable Iodine 158
17.2.3 Treatment with Radioiodine 159
17.2.3.1 Aspects of Radiation 159
17.2.3.2 Dosage Calculation and Therapy 160
17.2.3.3 Radiation Safety After Radioiodine Treatment 161
17.2.3.4 Consequences of Radioiodine Treatment 161
17.2.4 Surgery 162
17.2.4.1 Surgical Routines 162
17.2.4.2 Indications for Surgical Treatment 163
17.3 Laboratory Checks After Treatment for Hyperthyroidism 164
18 Graves’ Disease 165
18.1 Pathophysiology 165
18.2 Symptoms Specific to Graves’ Disease 165
18.3 Diagnosis 167
18.4 Treatment 168
18.4.1 Medical Treatment 168
18.4.2 Radioiodine Treatment 171
18.4.3 Surgical Treatment 173
18.4.3.1 Preoperative Treatment 173
18.4.3.2 The Surgical Technique 173
18.4.3.3 Postoperative Treatment and Follow-Up 174
18.4.3.4 Recurrence 174
18.5 Quality of Life 175
18.5.1 Neuropsychiatric Symptoms 175
18.5.2 Quality of Life Studies 175
19 Thyroid-Associated Ophthalmopathy 177
19.1 General Eye Symptoms in Thyrotoxicosis 177
19.2 Eye Symptoms Specific to Graves’ Disease 177
19.3 Risk Factors and Pathophysiology 178
19.4 Symptoms and Diagnosis 179
19.5 Practical Management 184
19.6 Clinical Activity Score 185
19.7 The ATA Classification 186
19.8 TAO in Autoimmune Chronic Thyroiditis 186
19.9 Euthyroid TAO 186
19.10 Choice of Therapy for Hyperthyroidism in Patients with Ophthalmopathy 187
19.11 Treatment Considerations 187
19.11.1 Practical Aspects 187
19.11.2 Specific Precautions 188
19.12 Follow-Up 190
20 Autonomous Adenoma 191
20.1 Definition and Prevalence 191
20.2 Pathophysiology 192
20.3 Specific Symptoms 192
20.4 Diagnosis 193
20.5 Treatment – General Considerations 193
20.6 Surgical Treatment 194
20.7 Radioiodine Treatment 195
21 Toxic Multinodular Goitre 196
21.1 Development of Toxic Nodular Goitre 196
21.2 Specific Symptoms and Clinical Picture 197
21.2.1 Nontoxic Multinodular Goitre 197
21.2.2 Transition from Nontoxic Multinodular Goitre to Toxic Multinodular Goitre 197
21.3 Diagnosis 198
21.4 Risk Groups/Risk Situations 200
21.5 Differential Diagnosis: Considerations 200
21.6 Treatment 200
21.6.1 Radioiodine Treatment 201
21.6.2 Surgical Treatment 201
21.6.3 Medical Treatment 202
22 Subclinical (Mild) Thyrotoxicosis 203
22.1 Nodular Goitre/Autonomous Adenoma 203
22.2 Graves’ Disease/Thyroiditis/hCG 204
22.3 Exogenous Causes 204
22.4 Suppressed TSH After Treatment for Thyrotoxicosis 204
22.5 Symptoms 204
22.6 Cardiac Effects 205
22.7 Effects on Bone 205
22.8 Psychological Effects 206
22.9 Clinical Recommendations 206
23 Thyrotoxicosis in the Elderly 207
24 Thyrotoxic Crisis/Thyroid Storm 209
24.1 Symptoms 209
24.2 Diagnosis 209
24.3 Treatment 210
25 Thyroiditis – Clinical Aspects 213
25.1 Thyroiditis with Autoimmune Mechanism 213
25.1.1 Hashimoto’s Disease 213
25.1.2 Atrophic Autoimmune Thyroiditis 214
25.1.3 Silent Thyroiditis and Postpartum Thyroiditis 214
25.1.4 Autoimmune Thyroiditis in Children and Adolescents 215
25.1.5 Focal Thyroiditis 215
25.1.6 Patients Receiving Interferon Treatment 215
25.2 Thyroiditis from Other Causes 216
25.2.1 Subacute Thyroiditis 216
25.2.2 Radiation-Induced Thyroiditis 216
25.2.3 Acute Bacterial Thyroiditis 216
25.2.4 Fibrous (Riedel) Thyroiditis 217
26 Subacute Thyroiditis (de Quervain´s Disease/Giant-Cell Thyroiditis) 218
26.1 Etiology 218
26.2 Symptoms 218
26.3 Progression 219
26.4 Diagnosis 219
26.5 Treatment 221
27 Other Causes of Thyrotoxicosis 222
27.1 Central (Secondary) Hyperthyroidism/TSH-Producing Pituitary Adenoma 222
27.2 hCG-Dependent Hyperthyroidism 223
27.3 Ectopic Production of Thyroid Hormones 224
27.4 Thyrotoxicosis Factitia 224
27.5 Iodine-Induced Hyperthyroidism 224
27.5.1 Exacerbation of Latent Graves´ Disease 225
27.5.2 Progress in Patients with Autonomous Adenoma 225
27.5.3 Iodine-Induced Thyroiditis 225
28 Nontoxic Goitre 227
28.1 Goitre and Its Causes 227
28.2 Goitre Due to Iodine Deficiency 227
28.3 Colloid-Rich Multinodular Goitre 228
28.3.1 Pathogenesis 228
28.3.2 Clinical Course 229
28.3.3 Clinical Examination 229
28.3.4 Investigative Methods 230
28.3.4.1 Hormones 230
28.3.4.2 Scintigraphy 230
28.3.4.3 Ultrasound Investigations 230
28.3.4.4 Radiological Investigation 230
28.3.4.5 Cytological Investigation 231
28.3.5 Treatment 231
28.3.5.1 Surgery 231
28.3.5.2 Medical Treatment 232
28.3.5.3 Radioidine Treatment 232
28.4 Intrathoracic Goitre 233
28.4.1 Clinical Presentation 233
28.4.2 Investigative Methods 233
28.4.3 Mapping 233
28.4.4 Assessment 234
28.4.5 Surgery 234
29 Thyroid Lumps 235
29.1 Incidence/Prevalence 235
29.2 Classification of Palpable Thyroid Lumps 235
29.3 Diagnosis of Thyroid Lumps 235
29.3.1 Medical History and Clinical Examination 235
29.3.2 Biochemical Work-Up 237
29.3.3 Imaging Investigations 237
29.3.4 Morphological Diagnostics: Fine-Needle Aspiration Cytology 238
29.4 Treatment of Palpable Thyroid Lumps 238
29.4.1 Palpable Lumps with Benign Cytology 238
29.4.2 Lumps with Follicular Neoplasia, Unclear Cytology or Nondiagnostic Samples After Fine-Needle Biopsy 239
29.4.3 Thyroid Cysts 239
29.4.4 Autonomously Functioning Lumps 239
29.4.5 Suppressive Treatment with Thyroxine 239
29.5 Investigation Algorithm 240
30 Thyroid Cancer 241
30.1 Classification of Thyroid Tumours 241
30.2 Characteristics of Common Thyroid Tumours 242
30.3 Epidemiology 243
30.4 Risk Factors 244
30.4.1 Hereditary Factors 244
30.4.2 Oncogenes and Tumour Suppressor Genes 245
30.4.3 Radiation 245
30.4.4 Treatment with I-131 246
30.4.5 Iodine 246
30.5 Diagnostic Investigation 247
30.6 Prognostic Factors 247
30.6.1 Age 248
30.6.2 Gender 248
30.6.3 Lymph Node Metastases 248
30.7 Prognostic Classification System 249
30.8 Treatment 251
30.8.1 Surgical Treatment 251
30.8.2 Treatment with I-131 252
30.8.2.1 Iodine Uptake 252
30.8.2.2 Importance of TSH in I-131 Treatment 252
30.8.2.3 Significance of Low Iodine Intake 253
30.8.2.4 Administered Radioiodine Activity 253
30.8.2.5 Radioiodine Treatment After Surgery 253
30.9 Follow-Up 254
30.9.1 Biochemical Assessment 254
30.9.2 Ultrasound 254
30.9.3 PET 255
30.9.4 TSH Suppression with Thyroxine 255
31 The Thyroid and Pregnancy 257
31.1 Maternal Physiology During Pregnancy 257
31.2 TSH, T4 and T3 During Pregnancy 258
31.3 Maternal/Placental Interaction 260
31.4 Thyroid Function in Mother and Foetus 260
31.5 The Thyroid and Fertility 262
31.6 Hypothyroidism and Pregnancy 263
31.6.1 Women with Previously Undiagnosed Hypothyroidism 263
31.6.2 Women Already Receiving Thyroxine Substitution 264
31.7 Hyperthyroidism and Pregnancy 265
31.7.1 Treatment of Hyperthyroidism 266
31.7.1.1 Medical Treatment 266
31.7.1.2 Surgical Treatment 267
31.8 Goitre and Palpable Lumps in the Thyroid 268
31.9 Development of Thyroid Diseases During the Postnatal Period 269
31.9.1 Diagnosis of Thyroid Dysfunction Postnatally 269
31.9.2 Graves´ Disease 269
31.9.3 Postpartum Thyroiditis and Primary Hypothyroidism 270
32 Thyroid Disease in Adolescents 272
32.1 Goitre 272
32.2 Autoimmune Thyroiditis and Hypothyroidism 273
32.2.1 Causes and Occurrence 273
32.2.2 Symptoms 273
32.2.3 Diagnosis 273
32.2.4 Progression 274
32.2.5 Treatment 274
32.3 Hyperthyroidism/Thyrotoxicosis 274
32.3.1 Causes and Occurrence 274
32.3.2 Symptoms 275
32.3.3 Diagnosis 275
32.3.4 Treatment 275
32.4 Palpable Thyroid Lumps 276
33 Medicines and Other Medical Preparations 278
33.1 General 278
33.2 Iodine 278
33.3 Amiodarone 278
33.3.1 Pharmacology 278
33.3.2 Pathophysiology 279
33.3.3 The Prevalence of Thyroid Function Disturbances in Amiodarone Treatment 279
33.3.4 Early Effects 279
33.3.5 Hypothyroidism 280
33.3.6 Amiodarone-Induced Thyrotoxicosis 280
33.3.7 Treatment 281
33.3.8 Amiodarone and the Thyroid – General Aspects 281
33.4 Other Iodine-Containing Preparations 282
33.5 Antithyroid Drugs 283
33.6 Lithium 283
33.7 Oestrogen 284
33.8 Interferon 284
33.9 Carbamazepine/Fenantoin 284
33.10 Miscellaneous 285
33.11 Medicines that Can Inhibit Thyroxine Absorption 285
34 Thyroid Hormone Resistance 286
Index 289