Thyroid pathophysiology

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Thyroid pathophysiology



Introduction


Thyroxine (T4) and tri-iodothyronine (T3) are together known as the ‘thyroid hormones’. They are synthesized in the thyroid gland by iodination and coupling of two tyrosine molecules whilst attached to a complex protein called thyroglobulin. T4 has four iodine atoms while T3 has three (Fig 44.1).



The thyroid gland secretes mostly T4 whose concentration in plasma is around 100 nmol/L. The peripheral tissues, especially the liver and kidney, deiodinate T4 to produce approximately two-thirds of the circulating T3, present at a lower concentration of around 2 nmol/L. Most cells are capable of taking up T4 and deiodinating it to the more biologically active T3. It is T3 that binds to receptors and triggers the end-organ effects of the thyroid hormones. Alternatively, T4 can be metabolized to reverse T3 (rT3), which is biologically inactive. By modulating the relative production of T3 and rT3, tissues can ‘fine tune’ their local thyroid status. Exactly how this is accomplished is not yet fully understood.



Goitre


A goitre is an enlarged thyroid gland (Fig 44.2). This may be associated with hypothyroidism, hyperthyroidism or a euthyroid state. Globally, iodine deficiency is the commonest cause of goitre. The WHO estimates that approximately 2 billion people have an inadequate iodine intake making it the commonest preventable cause of neuro-developmental problems. In many developed countries this problem has been overcome by the addition of iodine to a staple food such as iodised salt.




Thyroid hormone action


Thyroid hormones are essential for the normal maturation and metabolism of all the tissues in the body. Their effects on tissue maturation are most dramatically seen in congenital hypothyroidism, a condition which, unless treated within 3 months of birth, results in permanent brain damage. Hypothyroid children have delayed skeletal maturation, short stature and delayed puberty.


Thyroid hormone effects on metabolism are diverse. The rates of protein and carbohydrate synthesis and catabolism are influenced. An example of the effect of thyroid hormones on lipid metabolism is the observation of a high serum cholesterol in some hypothyroid patients. This is a consequence of a reduction in cholesterol metabolism due to down regulation of low-density lipoprotein (LDL) receptors on liver cell membranes, with a subsequent failure of sterol excretion via the gut.



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Jun 18, 2016 | Posted by in BIOCHEMISTRY | Comments Off on Thyroid pathophysiology

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