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Serum Ghrelin Levels Are Increased in Hypothyroid Patients and Become Normalized by L-Thyroxine Treatment

Medical Department M (Endocrinology and Diabetes) (S.G., E.T.V., A.L.D.R., N.M., J.W., J.O.L.J.), Department of Clinical Physiology and Nuclear Medicine (L.C.G.), and Medical Department C and Department of Pharmacology (J.R.), Aarhus University Hospital, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Signe Gjedde, M.D., Medical Department M, Aarhus University Hospital, Nørrebrogade 42, DK-8000 Aarhus C, Denmark. E-mail: signegjedde{at}dadlnet.dk.

Context: An interaction between ghrelin, which is implicated in the regulation of short- and long-term energy balance, and thyroid function has been reported in hyperthyroidism in which ghrelin levels are reversibly suppressed. We measured serum ghrelin levels and metabolic indices in hypothyroid patients before and after L-thyroxine replacement.

Patients and Methods: Eleven patients were examined twice: 1) in the hypothyroid state and 2) after at least 2 months of euthyroidism. Ten healthy subjects served as a control group. Ghrelin was measured in conjunction with indirect calorimetry and a hyperinsulinemic euglycemic clamp.

Results: Serum ghrelin levels were increased by 32% under basal conditions in the hypothyroid state (PRE) as compared with posttreatment (POST) (picograms per milliliter): 976.4 ± 80.8 vs. 736.8 ± 67.1 (P < 0.001). This difference prevailed during the clamp, but a decline was observed in both states: 641.4 ± 82.2 vs. 444.3 ± 66.8 µg/ml (P = 0.005). The hypothyroid state was associated with decreased resting energy expenditure, increased respiratory quotient, and insulin resistance. Serum ghrelin levels as well as the metabolic aberrations became normalized after L-thyroxine replacement as compared with the control subjects.

Conclusion: Serum ghrelin levels are reversibly increased in hypothyroid patients. It remains to be investigated whether this represents a direct effect of iodothyronines on ghrelin secretion or clearance or a compensatory response to the abnormal energy metabolism in hypothyroid patients.