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THYROID DISEASE

BIOCHEMISTRY

mprasadnaidu
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THYROID DISEASE

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  1. Disorders of thyroid & parathyroid glands M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar

  2. Disorders of thyroid & parathyroid glands • 1. Hyperthyroidism • 2. Thyroid Adenoma • 3. Grave’s disease

  3. Hyperthyroidism • Causes: • Due to the presence of TSH like substances – proved by RIA studies • The conc of TSH was found to be 0/less in plasma of Hyperthyroidism patients • The TSH like substances are Abs which bind with same membrane receptors of TSH • These substances activate c-AMP system ↑T4 • These Abs act for long time (12hrs) (TSH-1hr) • The ↑ of high T4 caused by Abs suppresses TSH production • Usually these Abs are developed b/cos autoimmunity

  4. Thyroid Adenoma • Some times – localised tumor develops in Thyroid tissue called Thyroidadenoma • TA secretes large quantities of T4&T3 • It is not associated with autoimmunity • As far as this adenoma remains active, the other parts of Thyroid gland will not secrete the hormone. • This is b/cos the hormone from Adenoma ↓ depresses the production of TSH

  5. Grave’s disease • Autoimmune disease • Normally TSH combines with surface receptors of thyroid cells  syn of T4 • But in GD , the TSH autoAbs (B-TSAB) produced by B-lymphocytes (Plasma cells) activate the TSH-receptors & ↑ secretion of T4

  6. Symptoms of Hyperthyroidism • Intolerance to heat ( due to ↑ BMR) • ↑ sweating ( due to vasodialation) • ↓ body wt ( Fat metabolism) • ↑ motility of GIT  diarrhoea • Muscular weakness  ↑protein catabolism • Nervousness, extreme fatigue, inability to sleep, mild tremor in the hands, psychoneurotic symptoms such as extreme anxiety/worry (stimulation of CNS) • Enlargement of Thyroid gland i.e, Toxic goiter • Exophthalmos: Autoimmune • some degree of protrusion of eye balls – if severe blindness develops due to • i)protrusion of eye ball stretches the optic nerve • Ii) eye lids cannot be closed  dry  infection

  7. hypothyroidism • ↓ secretion of Thyroid hormones • Autoimmune disease which causes destruction of Gland • In most patients it starts as the glandular inflammation called – Thyroiditis • Thyroiditis  fibrosis of the gland • Hypothyroiditis Myxedema (adults) Cretinism (Children)

  8. Myxedema • Due to hypothyroidism in adults • Causes: occurs in severe conditions – complete lack of thyroid hormones • Signs & symptoms: • Swelling of the face • Bagginess under the eyes • Non-pitting type of edema:- when pressed it does not make pits and the edema is hard (accumulation of Pro+cho.SO4 which form hard tissue with ↑ accumulation of fluid) • Atherosclerosis: ↑ cholesterol – blood ↑ bp

  9. Myxedema • Other general symptoms: • Fatigue & muscular sluggishness • Extreme somnolence ( 14-16 hrs/day) • Menorrhagia & polymenorrhea • ↓ Cordiovascular functions such as ↓heart rate, ↓ force of contraction of heart ↓ crodiac out put , ↓ blood volume • ↑Body wt • Constipation • Mental sluggishness • ↓ hair growth • Scaliness of the skin • Frog like husky voice

  10. Cretinism • Children • Causes: congenital absence of thyroid gland (genetic disorder or lack of I2 in diet) • Features: • The newborn baby may appear normal at birth (due to supply of T4 from mother) • But after few weeks – starts developing sluggish movements croacking sound while crying  mentally retarded • Skeletal growth is more affected than soft tissues • Tongue becomes so big – affects swallowing & breathing • Stunted growth

  11. Differences b/n Cretinism & Dwarfism

  12. Goiter • Enlargement of thyroid gland • Occurs both in hypothyroidism & Hyperthyroidism • Goiter in Hyperthyroidism  Toxic Goiter • Due to tumor of the gland – Size ↑ - ↑ number of hormones secreting cells ↑ hormone level – Toxic Goiter • Goiter in hypothyroidism –non toxic Goiter • Only enlargement of gland – hormone secretion is ↓

  13. Goiter • Based on the cause, Non-toxic Goiter is of 2 types • i) Endemic Colloid Goiter:- • Due to lack of I2 – I2 intake <50µg/day • Therefore no formation of hormones • By feed back mechanism, hypothalamus and anterior pituitary are stimulated • This ↑ secretion of TRH and TSH  secretion of TGb Follicles • As there are no hormones to be cleaved, ↑ accumulation in the follicles • Therefore ↑ size of the gland • In Swiss, Alps, Andes, Great region of US and in India – Kashmir Valley Soil does not I2↓ • Therefore Food stuffs lack I2 – very common before the introduction of iodized salts

  14. Idiopathic Non-toxic Goiter • Enlargement of Thyroid gland occurs even without I2 deficiency • Exact cause not known • These patients are first affected by Thyroiditis which reduce synthesis of Thyroid hormones • Therefore secretion of TSH ↑ • ↑ Size of the gland • In some persons the abnormal enzyme system leads to Goiter(due to deficiency of enzymes like peroxidase, iodinase and deiodinase which are required synthesis of T3&T4)

  15. Idiopathic Non-toxic Goiter • Goitrogenic Substances: ( Goitrogens) • Eg: Goitrin • Contains antithyroid substances like propylthiouracil • Therefore TSH secretion ↑ enlargement of Thyroid gland • Goitrogens  in turnips, cabbage, soyabeans • The goitrogens become active only during low I2 intake

  16. Treatment for Thyroid disorders • Treatment for Hyperthyroidism:- • 1. Surgical removal: Thyroidectomy • 2. Antithyroid substances: Thiocyanate, thiourylenes, high conc of inorganic iodides • Treatment of hypothyroidism: • Only treatment is administration of Thyroid extract/ ingestion of pure thyroxine ( tablet)

  17. Anti thyroid substances • Drugs which supress the secretion of T3&T4 • 1. Thiocyanate: the same active pump which transports I- into Thyroid cells, transports thiocyanate also • So thiocyanate competitively inhibits I2 transport • I2 transport is inhibited • ↓ synthesis of Thyroxine

  18. Thiourylenes • Thiourea related substances • Eg: Propylthiouracil and methimazole prevent the formation of T4 from iodides and Tyr • This is achieved by blocking peroxidase activity and partly by blocking coupling of MIT & DIT • During the use of these two antithyroid agents even though the synthesis of Thyroid hormone is inhibited , the formation of TGb is not stopped • The deficiency of the hor ↑ TSH secretion ↑ Size Thyroid gland with more secretion of TGb • TGb accumation in gland  enlargement  non-toxic G

  19. High conc of inorganic iodides • All phases of Thy.activity ↓ • ↓ release of Thyroxine • ↓ Size • ↓ blood supply • Therefore iodides are frequently administrated to hyperthyroid patients

  20. Thyroid function Tests • The most accurate diagnostic test is Direct measurement of conc of Free thyroid hormones in the plasma (T3&T4) • Measurement of BMR:- • In Hyperthyroidism, ↑ 30-60% • In hypothyroidism, ↓ 20-40% • The measurement of TRH and TSH:- • In Hyperthyroidism total absence of TRH & TSH (due to –ve feed back mechanism by the ↑level of Thyroid hormones)

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