THYROID PHYSIOLOGY



Iodide, a substrate for thyroid hormone synthe­sis, also plays an autoregulatory role in the me­tabolism of the thyroid gland. The normal gland contains approximately 10,000 |xg of iodine, which is predominantly organically bound. The minimal daily requirement of iodide is only about 200 |Ag (renal loss replacement). Iodide deficiency is a rare occurrence in the iodide-replete western world but remains the commonest cause of goiter (endemic goiter) in the world. Many patients with endemic goiter are mentally deficient owing to hypothyroidism dating from birth (cretinism) or suffer from retarded musculoskeletal develop­ment owing to thyroid hormone deficiency during childhood.

The thyroid gland concentrates iodide through a unique trapping mechanism to maintain a cell-to-plasma iodide ratio of about 50 to 1. Trapped iodide is rapidly oxidized by peroxidase to iodine and subsequently undergoes organification by io-dinating tyrosine residues on thyroglobulin to form MIT and DIT. Coupling of these compounds results in “the formation of T3 and T4. The secre­tory process is initiated by pinocytosis of thyro­globulin from the follicular lumen followed by the release of T4 and T3 from their storage form by proteolysis induced by lysosomal enzymes. The active hormones T4 and T3 are then secreted into the circulation. The thyroid gland is the only source for T4, whereas it contributes only about 20 per cent of the T3 produced daily. A number of chemicals interfere’ with thyroid gland metabolism. These effects have been ex­ploited for therapeutic purposes in the case of pro­pylthiouracil (PTU) and methimazole. Both drugs effectively block thyroid hormone synthesis and are utilized clinically in the treatment of hyper­thyroidism. Agents that are preferentially trapped by the thyroid (iodide, pertechnetate) are used diagnostically for gland imaging. Pharmacologic amounts of iodide will also inhibit thyroid gland synthesis and release of hormones. This inhibi­tory effect is generally of short duration in normal people, but if sustained it can lead to hypothy­roidism and compensatory goiter formation. Lith­ium has a similar effect to that of iodide. Its cur­rent extensive use in manic-depressive illness has lead to a significant problem with hypothyroid­ism in this patient group.
Thyroid hormones circulate in two forms, pro­tein-bound and free. Thyronine-binding-’ globulin (TBG), the principal carrier, binds about 70 per cent of the thyroid hormones under normal con­ditions. Other carrier proteins, thyroxine-binding pre-albumin (TBPA) and albumin, play a lesser role. A small but very important quantity of T4 (0.03 per cent) and T3 (0.3 per cent) is free and remains in rapid equilibrium with the protein-bound fraction. The metabolic state of the patient correlates with the free component rather than the total (bound) thyroid hormone level. Alterations in serum TBG concentration are common and ac­count for the majority of changes in serum total T4 not attributable to hyper- or hypothyroidism (Table 68-1). These changes in serum total T4 lev­els are not accompanied by changes in the free T4 concentration. Thus a measurement of free T4 or an index of free T4 is obligatory under these con­ditions in order to interpret accurately the signif­icance of a change in the total hormone value. During acute illness, however, factors that affect the affinity of TBG for T4 may reduce the total and occasionally the free T4 concentration.