Thyroid-stimulating hormone stimulates the preferential release of thyroxine (T 4) from the thyroid gland. T4 is then peripherally deiodinated into its active metabolite tri-iodothyronine (T3) or into reverse T3 (rT3) which is thought to be biologically inactive. Both T4 and T3 exert feedback inhibition at the pituitary and hypothalamic level. Critical illness is characterized by a low T 3 or 'sick euthyroid syndrome'. In mild and severe illness T3 production is rapidly decreased by inhibited conversion of T4 to T3. There is then a reciprocal increase in the inactive thyroid metabolite rT 3. With more sustained illness T4 levels may also fall because of reduced T4 binding to its carrier proteins leading to accelerated metabolism. More importantly, thyroid-stimulating hormone secretion is also suppressed; for example, the normal night-time surge in thyroid-stimulating hormone is not present in patients with sick euthyroid syndrome and the response of thyroid-stimulating hormone to thyrotropin-releasing hormone is frequently blunted. The degree of T3 suppression with concomitantly low thyroid-stimulating hormone concentrations correlates positively with disease severity and negatively with outcome. The changes in T3 and T4 concentrations also correlate inversely with changes in circulating catecholamine levels.
The pathogenesis of sick euthyroid syndrome remains unclear, although recent observations have indicated that interleukin 1 (IL-1) and tumor necrosis factor induce the changes observed in this syndrome. It remains questionable whether these alterations in tests of thyroid function reflect deficiency of thyroid hormone, although an increase in thyroid-stimulating hormone concentrations is viewed as a marker of recovery from life-threatening illness.
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