THYROID FUNCTION TEST 2_copy.pdf.smc.dr.maruf.sir
- 1. THYROID FUNCTION TEST DR. AHMED AL-MAARUF, ASSISSTANT PROFESSOR, DEPT. OF BIOCHEMISTRY
- 2. ▪ Located on either side of trachea below larynx. ▪ Synthesizes & secrets thyroid hormones ▪ From follicular cells- ▪ Thyroxine (T4)- 95 % ▪ Tri-iodothyronine (T3)- 5% ▪ From parafollicular cells- ▪ Calcitonin THYROID GLAND AND HORMONES
- 3. • Thyroid hormones are derived from amino acid tyrosine. • The thyroid gland uses iodine (from the diet, iodized salt, seafood) to produce thyroid hormones. • The two most important thyroid hormones are • 3,5,3′,5′- Tetra Iodothyronin or Thyroxine (T4) and • 3,5,3′ Tri-iodothyronine (T3). THYROID HORMONES
- 4. ▪ Thyroid hormones act on cells of every body tissue by combining with nuclear receptors and altering expression. ▪ Thyroid hormone is required for normal brain and somatic tissue development in the fetus and neonate. ▪ Control of the BMR & calorigenesis. ▪ Enhancement of mitochondrial metabolism of carbohydrate, protein & fat. ▪ Action on digestion, absorption of food. ▪ Promotion of sexual maturation. ▪ Action on CVS,CNS & respiratory function. ▪ Enhancing the adrenergic receptor sensitivity to catecholamine. FUNCTIONS OF THYROID HORMONES
- 5. REGULATION OF THYROID HORMONE SECRETION It is done by hypothalamo-pituitary-thyroid feedback mechanism.
- 6. BIOSYNTHESIS OF THYROID HORMONE • Site: in the colloid of thyroid gland. • Raw material: ▫ Iodine (daily intake - 140 micro gram/day) ▫ Amino acid – tyrosine ▫ Enzyme – thyroid peroxidase and other related enzymes • TSH stimulates the all steps of thyroid hormone synthesis. Colloid of thyroid follicle
- 7. BIOSYNTHESIS OF THYROID HORMONE • Thyroid hormones are derived from amino acid tyrosine. • Tyrosine is iodinated to 3 monoiodotyrosine (MIT) and 3, 5 diiodotyrosine (DIT). • One MIT condenses with one DIT to form one molecule T3 . • One DIT condenses with another DIT to form one molecule T4 .
- 8. ❑ Thyroid gland secretes- T4 (95%) & T3 (5%). ❑Thyroid hormones circulates in blood by binding with- ▪ Thyroxine binding globuline (TBG) ▪ Thyroxine binding pre albumin (TBPA) ❑ It is the free thyroid hormone which is- ▪ Physiologically active ▪ Determine thyroid status ▪ Is under control of hypothalamo pituitary thyroid feedback response. TRANSPORT OF THYROID HORMONE
- 9. 1. Intrathyroidal conversion 2. Peripheral conversion: ▪ mainly in liver, kidney and muscles ▪ Maximum conversion of thyroid hormone occurs peripherally 5 ׳Deiodinase ❑ T4 -------------------→ T3 (35%) 5 Deiodinase ❑ T4 -------------------→ rT3 (45%) 85% of T3 produced from T4 by peripheral conversion. CONVERSION OF THYROID HORMONE
- 10. ❑ TT4 - 62.00- 158.5 nmol/L ❑ FT4 - 9.00- 23.81 pmol/ L ❑ TT3 - 1.21- 3.08 nmol/L ❑ FT3 - 1.86- 6.43 pmol/L ❑ TSH - 0.40- 5 .00 mIU/L NORMAL RANGE OF THYROID HORMONE
- 11. Trait T4 T3 Production by thyroid gland Major (87%) Small amount (13%) Potency Less potent 3-5 times more potent Affinity to receptor Less More (10 times) Onset of a action Slow Rapid Duration of action Prolong Short Plasma half-life 6.5 days 1.5 days COMPARISON OF THYROID HORMONES
- 13. THYROID FUNCTION TESTS 1. TSH concentration. 2. Total T3 & T4 concentration. 3. FT3 &FT4 concentration. 4. Radio active iodine uptake(0.75µg/day). 5. Estimation of protein bound iodine (4-8µg/dl). 6. Thyroid antibody-Anti-TG, Anti-TPO. Thyroid follicular cells uptake radioactive I which was given orally & thyroid radioactivity measured at 6th and 24th hours. Anti Thyroglobulin antibody , Anti Thyroid Peroxidase antibody and TSH Receptor bloking antibody.
- 14. 7. TRH Test 8. TSH stimulation test 9. T3 Supression test 10. Other nonspecific tests: ▪ Serum cholesterol ▪ Serum calcium Basal TSH is measured , then IV TRH given & again TSH is measured at 20th & 60th minutes. T3 is given for 5 days , then RAIU is measured. Baseline RAIU is measured , then IV TSH given & again RAIU is measured. THYROID FUNCTION TESTS
- 15. HYPOTHYROIDISM A. Primary Hypothyroidism: (due to intrinsic defect in thyroid gland) ▪ Iodine deficiency ▪ Autoimmune (Hashimoto’s Thyroiditis) ▪ Surgery/ radiation ▪ Anti thyroid drugs ▪ Hemochromatosis, sarcoidosis ▪ Viral/ bacterial infection. B. Secondary Hypothyroidism: (Due to pituitary defects or hypothalamic defects) B. Thyroid Hormone Resistance Syndrome Two types: ▪ Goitrous ▪ Non Goitrous
- 16. GOITER It is the enlargement of thyroid gland due to any cause Types and causes: 1. Diffuse goiter ➢ Iodine dificiency ➢ Grave’s disease ➢ Thyroiditis ➢ Thyroid lymphoma 2. Nodular goiter (solitary or multinoduler) > Adenoma > Carcinoma
- 17. HYPOTHYROIDISM
- 18. ❑ Lethargy,Tiredness. ❑ Slow and husky voice. ❑ Dryness & coarsening of Hair & skin ❑ Weight gain, Puffy face, bagginess under eye. ❑ Cold intolerance, Decrease BMR. ❑ Menstrual irregularities& infertility. ❑ Slow relaxation of muscles ,tendon reflexes ❑ Many other associated signs including anaemia, dementia,constipaton,bradycardia,muscle stiffness,carpal tunnel syndrome,galactorrhoea. FEATURES OF HYPOTHYROIDISM ▪ Dry, coarse, sparse hair. ▪ Thin lateral eyebrow ▪ Pallor & puffy dull face. ▪ Dry & coarse skin. Myxedema (Adult hypothyroidism) Deposition of mucopolysaccharide under skin binds with water producing indurated oedema & myxedematous appearance.
- 19. FEATURES OF HYPOTHYROIDISM CRETINISM Children with hypothyroidism from birth or before birth are called cretins. Causes- Maternal iodine deficiency, fetal thyroid dysgenesis, inborn error of thyroid synthesis etc. Features-They have reduced growth & mental retardation. ❑ Potbelly. ❑ Hypotonia. ❑ Coarse face.
- 20. ❑Measurement of TSH & Thyroid hormones: ▪ High TSH with low free T4 :Primary Hypothyroidism. ▪ Low TSH with low free T4 :Secondary Hypothyroidism. ▪ High TSH with normal free T4: Subclinical hypothyroidism. ❑RAIU test: ▪ Low uptake. ❑Measurement of Thyroid autoantibodies: ▪ Positive in autoimmune thyroiditis. ❑TRH test: ▪ Exaggerated response: Primary Hypothyroidism. ▪ No response : Pituitary Hypothyroidism. ▪ Delayed response : Secondary Hypothyroidism. LABORATORY FINDINGS OF HYPOTHYROIDISM
- 21. ❑TSH stimulation Test: ▪ No Response: Primary Hypothyroidism. Positive Response: Secondary Hypothyroidism. ❑Nonspecific laboratory findings associated with hypothyroidism: ▪ Serum enzymes: raised creatine kinase,AST, LDH ▪ Hypercholesterolaemia . ▪ Anaemia: normochromic normocytic or macrocytic. ▪ Hyponatraemia. LABORATORY FINDINGS OF HYPOTHYROIDISM
- 22. Subclinical Hyporthyroidism It is the clinical condition where – ❑ TSH persistently elevated (6 to 12 weeks longer) ❑ Free T4 within reference interval or lower limit of the interval. These group of people have risk to progression to overt Thyroid failure. SUBCLINICAL HYPOTHYROIDISM
- 23. HYPERTHYROIDISM It is the clinical condition produced by excess circulating thyroid hormones due to their excess synthesis. A. Primary Hyperthyroidism (due to intrinsic defect in thyroid gland) • Graves disease • Multi nodular toxic goiter • Solitary toxic thyroid nodule • Thyroiditis • Follicular carcinoma of thyroid B. Secondary Hyperthyroidism (due to pituitary defects or hypothalamic defects) • TSH secreting pituitary adenoma • TSH secreting trophoblastic tumor
- 24. HYPERTHYROIDISM
- 25. ❑ Metabolic effect: increased BMR, heat intolerance, weight loss ❑ Cardiovascular effect: tachycardia, palpitation ❑ Neurological effect : tremor, nervousness, excessive sweating, irritability, psychoisis ❑ Muscular effects: proximal myopathy, muscle atrophy ❑ Reproductive effects: menstrual irregularities, infertility, impotency, loss of libido. ❑ Ocular effect : exophthalmos, ophthalmoplegia. EFFECTS OF HYPERTHYROIDISM
- 26. HYPERTHYROIDISM TSH T4 T3 Interpretation Undetectable Raised Raised Primary thyrotoxicosis Undetectable Normal Raised Primary T3 toxicosis Undetectable Raised Low ,N,R Sick Euthyroidism Undetectable Normal Normal Sub clinical thyrotoxicosis
- 27. A.Measurement of TSH & Thyroid hormones: ▪ Low TSH & High free T4 & free T3: Primary Hyperthyroidism/Thyrotoxicosis ▪ Low TSH & normal free T4 & High free T3:T3 hyperthyroidism /T3 thyrotoxicosis. ▪ High TSH & High free T4 & T3: Secondary hyperthyroidism ▪ Low TSH & normal Free T4 & T3: Subclinical Hyperthyroidism. B.RAIU test: Increased except in Thyroiditis(decreased). C.Measurement of Thyroid auto antibodies: Positive in Graves’ Disease. LABORATORY FINDINGS OF HYPERTHYROIDISM
- 28. D.T3 suppression Test: Failure to suppress thyroid activity following T3 supplementation Indicates Graves’ Disease. E.Non specific laboratory findings associated with Hyperthyroidism: ▪ Serum enzymes: Raised ALT,GGT,& ALP from liver & bone. ▪ Raised bilirubin ▪ Mild hypercalcaemia. ▪ Hyponatraemia. LABORATORY FINDINGS OF HYPERTHYROIDISM
- 29. FINDINGS OF TFT
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