Effect of dexamethasone on TSH secretion induced by TRH in human obesity

Background: The presence of an abnormally high thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) makes it difficult to distinguish some euthyroid obese subjects from subclinically hypothyroid obese patients, Here, we examine whether such distinction may be achieved after treatment with glucocorticoids, which inhibit TSH secretion at the hypothalamic-pituitary level. Methods: TRH tests (200 pg as an intravenous bolus injection) were performed in 30 age- and weight-matched, obese, but otherwise healthy, men. All subjects were tested again with TRH after treatment with dexamethasone (dex) (2 mg/d in four divided doses orally for 3 days). Results: In all subjects, total thyroxine and triiodothyronine concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I(n=10), euthyroid subjects; group II (n=10), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n=10), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothyroid-ism). Basal TSH levels were 1.8 +/-0.4 mU/L in group I, 1.7 +/-0.3 in group II, and 6.0 +/-0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment > 15 mU/L) and were significantly higher than in group I. After the second treatment with TRH, pretreatment with dex significantly decreased both basal TSH levels and peak TSH responses to TRH in all groups. However, a striking percentage decrease (> 50%) in TRH-induced peak TSH responses was observed in euthyroid obese subjects of groups I and II, whereas hypothyroid subjects of group III showed only a slight decrement (< 25%). Conclusions: The sensitivity of the TSR secretory system to glucocorticoid inhibitory action is preserved in obese subjects with abnormally elevated TSH response to TRH, but not in subclinically hypothyroid obese patients. The TRH plus dex test might be useful in future studies to understand the mechanisms underlying alterations in TSH secretion in obesity.