Modern Laboratory Investigation of Thyroid Diseases: UNI-MED SCIENCE

1. Assay methods and clinical test procedures 12 1.1. General assay procedures for thyroid diseases 12 1.2. Thyroid hormones 13 1.2.1. Thyroid-stimulating hormone (TSH, thyrotropin) 13 1.2.1.1. TSH screening in neonates 14 1.2.1.2. TRH test (TSH stimulation test with TRH) 14 1.2.2. Determination of free thyroxine (fT4, tetraiodothyronine) and free triiodothyronine (fT3) 15 1.2.3. Determination of total thyroxine (TT4, total tetraiodothyronine) and total triiodothyronine (TT3) 16 1.3. Thyroxine-binding globulin (TBG) 17 1.4. Reverse T3 (rT3) 17 1.5. Thyroid autoantibodies 18 1.5.1. Thyroid peroxidase antibodies (anti-TPO antibodies) 18 1.5.2. Thyroglobulin antibodies (anti-hTG antibodies, TAbs) 18 1.5.3. Thyroid autoantibodies to the TSH receptor (TRAb, anti-TSHR Ab) 18 1.6. Tumour markers 19 1.6.1. Thyroglobulin (hTG) 19 1.6.2. Calcitonin (hCT, thyrocalcitonin) 20 1.6.2.1. Pentagastrin stimulation test 20 1.6.2.2. Calcium stimulation test 21 1.6.3. Chromogranin A (CgA) 21 1.7. References 22 2. Euthyroid goitre 24 2.1. Introduction and definition 24 2.2. Aetiology 24 2.3. Clinical presentation 24 2.4. Laboratory investigations 24 2.4.1. Synthesis, homeostasis and protein binding of thyroid hormones 24 2.4.2. Confounders 25 2.4.3. Clinical interpretation of test results 26 2.4.4. Reference ranges 26 2.4.5. Reference ranges and their relationship with age 26 2.4.6. Calcitonin determination in the context of cold thyroid nodules 27 2.5. References 27 3. Hyperthyroidism 30 3.1. Introduction and definition 30 3.2. Aetiology 30 3.3. Clinical presentation 30 3.4. Laboratory investigations 30 3.4.1. Methods of determination 30 3.4.2. Thyroid hormones 30 3.4.3. Hyperthyroidism and pregnancy 31 3.4.4. Postpartum thyroiditis 32 3.4.5. Amiodarone-induced hyperthyroidism 32 3.5. References 32 4. Graves' (Basedow's) disease 36 4.1. Introduction and definition 36 4.2. Aetiology 36 4.3. Clinical presentation 37 4.4. Laboratory investigations 38 4.4.1. Autoantibodies to the TSH receptor 38 4.4.1.1. Early TRAb assays 38 4.4.1.2. Fluid-phase TRAb assays (first generation) 39 4.4.1.3. Solid-phase TRAb assays (second generation) 39 4.4.1.4. M22-based TRAb assays (third generation) 40 4.4.1.5. TRAb bioassays 40 4.4.2. Autoantibodies to thyroglobulin and autoantibodies to thyroid peroxidase 41 4.4.2.1. Clinical importance of TRAbs in the diagnosis and monitoring of Graves' disease 41 4.4.2.2. Clinical importance of TPO antibodies and TAbs in Graves' disease 43 4.5. Summary 43 4.6. References 43 5. Endocrine ophthalmopathy 46 5.1. Introduction and definition 46 5.2. Aetiology 46 5.3. Clinical manifestation and classification of EO 46 5.4. Laboratory investigations 49 5.4.1. TSH, fT4, fT3 49 5.4.2. Thyroid-specific antibodies 49 5.5. Management plan for EO 51 5.6. References 51 6. Hypothyroidism 54 6.1. Introduction and definition 54 6.2. Aetiology 54 6.3. Clinical presentation 54 6.4. Laboratory investigations 54 6.4.1. Thyroid hormones 54 6.4.2. Non-thyroidal illness syndrome 54 6.4.3. Thyroid autoantibodies 55 6.4.4. Assessment of prognosis in autoimmune thyroiditis 56 6.4.5. Congenital hypothyroidism 56 6.5. References 57 7. Thyroid carcinomas of follicular cell origin 60 7.1. Introduction and definition 60 7.2. Aetiology 60 7.3. Clinical presentation 61 7.4. Laboratory investigations 61 7.5. References 66 8. Medullary thyroid carcinoma 70 8.1. Introduction and definition 70 8.2. Aetiology 70 8.3. Clinical presentation 71 8.4. Laboratory investigations 71 8.4.1. Calcitonin as a tumour marker in thyroid nodules (calcitonin screening) 73 8.4.2. Calcitonin as a tumour marker in treated MTC 73 8.5. References 75 9. Abbreviations 78 Index 79