PITUITARY THYROTROPIN HOMEOSTASIS IN MAN

Abstract

Serum thyroid hormone concentrations and the amounts of thyroid hormone available to peripheral tissues are maintained within narrow limits by thyroid hormone-TSH Interaction. TSH synthesis In the anterior pituitary and Its secretion Into the peripheral circulation are under positive control by hypothalamic thyrotropin-releasing hormone (TRH) and under negative feedback by thyroid hormones, designed to counteract thyroid hormone fluctuations and to maintain euthyroidism. Current concepts of thyroid hormone production and control were established prior to the availability of good assays for TSH and fT4. Since 1984, It Is accepted that pituitary thyrotrophs are exquisitely sensitive to small changes In serum thyroid hormone concentrations. A minor rise or fall of thyroid hormones concentration determined from the estimates of free thyroxine Index (fT4I), elicits more than 10 times larger Inverse change In TSH release. With the availability of immunometric TSH assays with Improved detection of low TSH concentrations and direct measurements of free thyroid hormones (automated microparticle enzyme Immunoassay of free thyroxine and free trillodothyronine) this relationship has been re-examined. There exists an Inverse relationship between TSH and the free thyroid hormones : fT4 > fT4I >> fT3 In both ambulatory subjects and hospitalized patients. This relationship Is abolished when the patients are Ill enough to be warded In the Intensive care unit. Additionally, this tight TSH-fT4 association is not seen in newborn babies and Is not established by the time they are 6 weeks old. The weaker association between TSH - fT3 and the finding of aberrant values (in hyper-, normal, and hypothyroid subjects) while surprising, renders fT3 as an unlikely candidate for routine thyroid function assessment. When the recovery of suppressed or stimulated thyrotrophs to treatment are examined, there Is a clear Indication from the limited patient studies of great variability between patients. This underscores the well-known clinical notion that all therapy (Including thyroid disorders) has to be individualised. Clearly needed are studies on larger patient populations to examine how thyrotrophs respond to therapy.