Ghrelin affects the hypothalamus-pituitary-thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma.

Objective: Ghrelin promotes a positive energy balance, e.g. by increasing food intake. Stimulation of the activity of the hypothalamus-pituitary-thyroid (HPT) axis promotes a negative energy balance, e.g. by increasing energy expenditure. We therefore hypothesized that ghrelin suppresses the HPT axis in humans, counteracting its energy-saving effect.

Design And Methods: In this single-blind, randomized, cross-over study, we determined secretion patterns of free triiodothyronine (fT(3)), free thyroxine (fT(4)), TSH, and thyroid-binding globulin (TBG) between 2000 and 0700 h in 20 healthy adults (10 males and 10 females, 25.3+/-2.7 years) receiving 50 microg ghrelin or placebo at 2200, 2300, 0000, and 0100 h.

Results: FT(4) plasma levels were significantly higher after ghrelin administration than after placebo administration from 0000 h until 0620 h except for the time points at 0100, 0520, and 0600 h. TSH plasma levels were significantly lower from 0200 until the end of the study at 0700 h except for the time points at 0540, 0600, and 0620 h. The relative increase of fT(4) (area under the curve (AUC) 0130-0700 h (ng/dl x min): placebo: 1.31+/-0.03; ghrelin: 1.39+/-0.03; P=0.001) was much weaker than the relative decrease of TSH (AUC 0130-0700 h (mIU/ml x min): placebo: 1.74+/-0.12; ghrelin: 1.32+/-0.12; P=0.007). FT(3) and TBG were not affected.

Conclusions: This is the first study to report that ghrelin affects the HPT axis in humans. The early fT(4) increase was possibly induced by direct ghrelin action on the thyroid where ghrelin receptors have been identified. The TSH decrease might have been caused by ghrelin-mediated inhibition at hypothalamic level by feedback inhibition through fT(4), or both.