Thyroid Hormone (TH) Structures Iodine Synthesis Secretion Metabolism Actions Hypo- & hyper- thyroidism Regulation

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Reverse T 3 Activity: T 3 > T 4 >> rT 3

iodine iodised salt … no salt sale in the shops of Dushanbe

Blood I–I– T3T4T3T4 90% T 4, 9% T 3, 1% rT 3 Thyroglobin

Regulation of Thyroid Hormone Concentrations Hypothalamus Cold (neonates) + + Anterior Pituitary + (1) Thyrotrophin Releasing hormone (TRH) Thyroid Gland Thyroid Stimulating Hormone (TSH) = Thyrotrophin Thyroid stimulating immunoglobulins (TSI) Thyroid hormone (TH)   1.  TH synthesis 2.  TH release 3.  number & size of cells

Metabolism T4T4 T3T3 rT 3 di-iodothyronines I – split off In: liver, kidney, pituitary 33% 45% * * * Regulation: T 4  T 3 inhibition by:propylthiouracil, propanolol (  blocker) glucocorticoids burns, trauma, renal failure, infarct  food intake

In Blood TH (T 4, T 3 ) + protein (thyroid binding globulin & others) Protein bound—T 4 or T 3 ) mostfree Free %small < 0.5 % gets into cells – biologically relevant

Thyroid Hormone Effects 4–5 times T 3 > T 4 >> rT 3 inert Mechanism:steroid hormone-like intracellular receptor modulation of RNA synthesis slow on-off effects

Thyroid Hormone Effects 1. Calorigenic actions effect on intermediary metabolism CHO / fat / protein effect on growth & development 2. Sympathomimetic effects facilitates actions of catecholamines (adrenalin, noradrenalin)

Calorigenic actions Heat producing e.g.  basal metabolic rate  heat production  energy use  O 2 consumption  number & size mitochondria

Metabolism Glucose:  rate absorption  uptake to cells Fat:  clearance lipoproteins  turnover Protein:  amino acid uptake  protein synthesis If T 4 or T 3 is too high, then protein catabolism Vitamins:B 12 absorption carotene  Vit. A If T 4 or T 3 is too high, then vitamin deficiencies

[ TH ] too little too much Protein Synthesis net Growth and development in utero & neonates CNS

Sympathomimetic Effects Relationship to catecholamines: some similar effects T 4 / T 3    adrenergic receptors (number & affinity) some effects of T 4 / T 3 can be treated with  blockers Excess T 4 / T 3 jumpy, anxious tremor pulse rate  bounding pulse, systolic P  diastolic P  peripheral vasodilation

Thyroid stimulating immunoglobulins = Thyroid stimulating hormone No negative feedback

Hypothyroidism: thyroid disease I – deficiency Fetus: impaired CNS development Child:  height, metal retardation & cold intolerance, impaired mental function, coarse hair, dry skin, husky voice,  reflexes

Goitre =  size thyroid gland euthyroid hyperthyroid e.g. TSI hypothyroide.g. I – deficiency, autoimmune thyroiditis I – deficiency  T 4 / T 3  negative feedback pituitary  TSH secretion  number & size thyroid cells

Summary T 4, T 3, (rT 3 ) synthesis in colloid negative feedback regulation pituitary & hypothalamus regulated metabolism free concentrations low but biologically relevant steroid hormone like – slow on-off actions: calorigenic on intermediary metabolism potentiation of catecholamines actions