Thyroid Function Test.pptx

Function of thyroid gland and biochemical assessment of its functions in health and diseases

1. Thyroid Function Test Prof. (Dr) Viyatprajna Acharya MD, PhD

2. A case of tinnitus traced back to Hypothyroidism

3. What shall we learn? Basic anatomy, physiology of thyroid gland Biochemical functions of thyroid hormone Biosynthesis and inhibitors Diagnostics Interpretation of reports

4. Anatomy of Thyroid gland A butterfly shaped gland on the front of neck , just under the voice box, with two lobes attached by an isthmus lying across the trachea. Brownish-red, butterfly shaped & highly vascular Situation : in front & side of lower part of neck opposite C5-7,T1 Extension : thyroid cart. to 6th tracheal ring on the anterior side of the neck. - overlays 2 nd – 4 th tracheal rings at isthmus Avg. width : 12-15 mm (each lobe) Avg. height : 50-60 mm long Avg. weight : 25-30 g in adults ** enlarges during Puberty & pregnancy.

5. HISTOLOGY Multiple acini or follicles lined by single layer of flat cells (inactive) or cuboidal / columnar cells (active) Acini contains colloid ( pink staining proteinaceous material ) & microvilli project into the colloid from the apices of thyroid cells C cells - der. From neuroectoderm as part of APUD cell - present along w/ thyroid cells Lobules are composed of follicles = structural units of the gland a layer of epithelium enclosing a colloid-filled cavity Colloid iodinated glycol-protein, iodothyroglobulin (precursor of thyroid hor.)

6. Physiology of thyroid Thyroid has rich blood supply - blood flow about 5ml/g / min. Primary function of the thyroid gland is the secretion of thyroid hormones : T4 is primary released hormone T3 at least 10 times more active T4 is converted to T3 peripherally Production of thyroid hormones is regulated in normal gland by TSH from the anterior pituitary gland.

7. T 4 /T 3 Conversion Sites The liver is the major site of extrathyroidal T 4 to T 3 conversion. Also occur in the kidney & other tissues .

8. Functions of thyroid gland Control of energy expenditure is the primary function 1mg Thyroid hormone—1000Kcal energy Growth, development and sexual maturation Stimulation of heart and contraction rate Stimulation of protein synthesis and carbohydrate metabolism Synthesis and degradation of cholesterol and TG ↑Vitamin requirement ↑ Sensitivity of β -adrenergic receptors to catecholamines Differentiation of fibroblast to fibrocyte and osteoblast to osteocyte

9. Thyroid-Releasing Hormone (TRH) Is secreted by hypothalamic neurons Is inhibited by high T3 & T4 Is the major positive regulator of TSH secretions

10. Biosynthesis of thyroid hormone 1. Uptake of iodine- Concentrates iodine up to 10,000 times Rate limiting step Uptake- Na + -K + ATPase and Na + -I - symport Inhibitors - Perchlorate, thiocyanate Stimulated by TSH Congenital defect- Iodide trapping defect 2. Oxidation of iodine- I - → I + Catalysed by Thioperoxidase- NADPH dependent reaction Stimulation- TSH Inhibition - Thiourea, thiouracil, Methimazole

11. Biosynthesis 3. Iodination- Thyroglobulin is iodinated Thyroglobulin contains 10% carbohydrate. 115 Tyr residues- 35 can be iodinated MIT & DIT are produced 4. Coupling- DIT + DIT → T4 (99%) DIT + MIT → T3 Congenital defect- Iodotyrosyl defect 5. Storage- considerable amount of hormone stored 8T4/ molecule- Colloid 6. Utilization- When needed, Tg (Thyroglobulin) is taken from acinar colloid back to the cell by pinocytosis

12. Utilization 7. Hydrolysis- Tgb-T4 Tgb + T4 Stimulation- TSH Inhibition- iodide 8. Release- T4 released to blood stream T3- deiodination at 5’ position rT3- deiodination at 5 position Protease H 2 O removed

13. Salvage of iodine Unutilized MIT & DIT are deiodinised and re-used inside the cell Deiodinase- enzyme Deficiency- DIT & MIT will be excreted in urine

14. Transport of thyroid hormones Carrier proteins- Thyroxine binding globulin (TBG) Thyroxine binding pre-albumin Albumin 99.97% of T4 and 99.7% T3 are in bound form Total protein bound iodine- 10mg/dl; T4 contains 8mg/dl

15. Mechanism of action T3 T4 cross the plasma membrane with the help of MCT-8 receptor Bind to THR α & THR β T3 has 15 times more affinity THRs (TR) form heterodimers with Nuclear receptors (RXR-retinoid X receptors) Then they interact with TRE- Thyroid hormone response element Transcription mRNA → Protein synthesis Defects in Tr β 1- thyroid resistance

16. Catabolism T1/2 of T4- 4-7 days T1/2 of T3- 1 day- highly active T 3 , T 4 Free I 2 Conjugated in liver partly and excreted through bile and urine By demination - Tetra- iodothyroacetic acid ( Tetrac ) Triiodo thyroacetic acid ( Triac ) Dehalogenase

17. Iodine deficiency disorders by age groups

18. Iodine excess Supplements, drugs, iodinated contrast agents Iodine excess may lead to Sub-clinical hypothyroidism Amiodarone induced thyrotoxicosis If Urinary iodine is adequate- iodised salt should be avoided

19. Thyroid tests Hormone concentrations Estimation of free hormone fraction- %fT4, %fT3, THBR Estimation of free hormone concentration- FreeT3, T4 index, FT4I, FT3I Serum binding proteins- TBG, TBPA (Transthyretin) Tests for AI thyroid disorders- anti-TPO Ab, Antithyroh = gol Other hormones and thyroid related proteins- TRH, calcitonin, thyroglobulin

20. I. Hormone concentrations Total T3, T4 FreeT3 (FT3), Free T4 (FT4) TSH rT3 TSH is more sensitive than T3 & T4 2fold change in FT4 causes 100 fold change in TSH RIA- Functional limit 1-2mU/L Immunometric assays-ELISA- 0.1-0.2 mU /L 3 rd gen immunometric assays- CLIA- <0.02mU/L 4 th gen- ECLIA- 0.001-0.002mU/L

21. Reference ranges T3- 70-204ng/dL T4- 4.6-10.5 μ g/dL TSH- 0.4-4.2 μ IU/ml FT3- 210-440 pg /dL FT4-0.8-2.7 ng/dL

22. Thyroglobulin Stored in follicular colloid ↑ level seen in- Thyroid adenoma Follicular & papillar CA of thyroid Subacute thyroiditis Hashimoto’s thyroiditis Grave’s disease

23. EXTRATHYROIDAL FACTORS THAT AFFECT THYROID FUNCTION Age Gender Ethnicity Season Radiation Medications Circadian rhythm – Highest at 2-4AM and lowest at 5-6PM Radiation-

24. Thyroid disorders Primary (Goitrous) hypothyroidism- AI thyroiditis- Hashimoto’s disease Post-thyroidectomy Primary (Non-Goitrous) hypothyroidism- Congenital Hypothyroidism- Iodine deficiency(all newborns are to be evaluated for TSH assay within 72hrs of birth) Absent/ectopic gland Dyshormonogenesis TSH receptor mutation

25. Secondary hypothyroidism- diseases of pituitary or hypothalamus Tumour, Trauma, irradiation Seehan’s syndrome Peripheral resistance to thyroid hormones Seehan’s syndrome

26. 1 Hyperthyroidism multinodular goitre Grave’s disease Increased binding proteins AutoAb-TSIg T4 toxicosis- toxic adenoma T3 toxicosis 2 Hyperthyroidism- TSH secreting tumours CG secreting tumours Gestational thyrotoxicosis

27. Non-thyroidal illness- acutely ill patients; T3, T4, TSH are lowered Euthyroid sick syndrome Euthyroid goitre- hyperplasia due to iodine deficiency, low normal hormones

28. For more PPT on Medical Biochemistry www.drvpacharya.com