Actions of Thyroid Hormone

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Chapter: Essential pharmacology : Thyroid Hormones And Thyroid Inhibitors

The actions of T4 and T3 are qualitatively similar and are nicely depicted in the features of hypo and hyperthyroidism. They affect the function of practically all body cells.



The actions of T4 and T3 are qualitatively similar and are nicely depicted in the features of hypo and hyperthyroidism. They affect the function of practically all body cells.


1. Growth and development


T4 and T3 are essential for normal growth and development. The most remarkable action is metamorphosis of tadpole to frog: the tail is usedup to build lungs, limbs and other organs. The action cannot be broadly labelled as catabolic or anabolic. It is exerted through a critical control of protein

synthesis in the translation of the genetic code. Congenital deficiency of T4 and T3 resulting in cretinism emphasizes their importance. The milestones of development are delayed and practically every organ and tissue of the body suffers. The greatest sufferer, however, is the nervous system. Retardation and nervous deficit is a consequence of paucity of axonal and dendritic ramification, synapse formation and impaired myelination. In adult hypothyroidism also, intelligence is impaired and movements are slow.


2. Intermediary Metabolism


Thyroid hormones have marked effect on lipid, carbohydrate and protein metabolism.


Lipid T4 and T3 indirectly enhance lipolysis by potentiating the action of catecholamines and other lipolytic hormones, probably by suppressing a phosphodiesterase increased cAMP: plasma free fatty acid levels are elevated. Lipogenesis is also stimulated. All phases of cholesterol metabolism are accelerated, but its conversion to bile acids dominates. Thus, hyperthyroidism is characterized by hypocholesterolemia. LDL levels in blood are reduced.


Carbohydrate Carbohydrate metabolism is also stimulated. Though utilization of sugar by tissues is increased (mainly secondary to increased BMR), glycogenolysis and gluconeogenesis in liver as well as faster absorption of glucose from intestines more than compensate it hyperglycaemia and diabetic like state with insulin resistance occur in hyperthyroidism.


Protein Synthesis of certain proteins is increased, but the overall effect of T3 is catabolic—increased amounts of protein being used as energy source. Prolonged action results in negative nitrogen balance and tissue wasting. Weight loss is a feature of hyperthyroidism. T3, T4 in low concentrations inhibit mucoprotein synthesis which so characteristically accumulates in myxoedema.


3. Calorigenesis


T3 and T4 increase BMR by stimulation of cellular metabolism and resetting of the energystat. This is important for maintaining body temperature. However, metabolic rate in brain, gonads, uterus, spleen and lymph nodes is not significantly affected. The mechanism of calorigenesis was believed to be uncoupling of oxidative phosphorylation: excess energy being released as heat. However, this occurs only at very high doses and is not involved in mediating the physiological actions of T3, T4. Dinitrophenol uncouples oxidative phosphorylation, but has no thyroid-like activity.


4. CVS


T3 and T4 cause a hyperdynamic state of circulation which is partly secondary to increased peripheral demand and partly due to direct cardiac actions. Heart rate, contractility and output are increased resulting in a fast, bounding pulse. T3 and T4 stimulate heart by direct action on contractile elements (increasing the myosin fraction having greater Ca2+ ATPase activity) and probably by up regulation of β adrenergic receptors. Atrial fibrillation and other irregularities are common in hyperthyroidism. Thyroid hormones can also precipitate CHF and angina. BP, specially systolic, is often raised. Myocardial O2 consumption can be markedly reduced by induction of hypothyroidism.


5. Nervous System


T3, T4 have profound functional effect on CNS. Mental retardation is the hallmark of cretinism; sluggishness and other behavioral features are seen in myxoedema. Hyperthyroid individuals are anxious, nervous, excitable, exhibit tremors and hyperreflexia.


6. Skeletal Muscle


Muscles are flabby and weak in myxoedema, while thyrotoxicosis produces increased muscle tone, tremor and weakness due to myopathy.


7. GIT


Propulsive activity of gut is increased by T3/T4. Hypothyroid patients are often constipated, while diarrhoea is common in hyperthyroidism.


8. Kidney


T3 and T4 do not cause diuresis in euthyroid individuals, but the rate of urine flow is often increased when myxoedematous patients are treated with it.


9. Haemopoiesis


Hypothyroid patients suffer from some degree of anaemia which is restored only by T4 treatment. Thus, T4 appears to be facilitatory to erythropoiesis.


10. Reproduction


Thyroid has an indirect effect on reproduction. Fertility is impaired in hypothyroidism and women suffer from oligomenorrhoea. Normal thyroid function is required for maintenance of pregnancy and lactation.


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