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Acute Pharmacological Reduction of Plasma Free Fatty Acids Enhances the Growth Hormone (GH)-Releasing Hormone-Mediated GH Secretion in Patients with Cushing’s Syndrome¹

Division of Endocrinology, Hospital Virgen del Rocio (A.L.-C., R.A., L.M.J.), and Hospital Virgen de Valme (I.F.L.), Sevilla, Spain E-41013; and Endocrine Section, Complejo Hospitalario Universitario de Santiago Department of Medicine (F.F.C.) and Department of Physiology (C.D.), University of Santiago de Compostela, Spain E-15780

Address all correspondence and requests for reprints to: F. F. Casanueva, M.D., Ph.D., PO Box 563, E-15780 Santiago de Compostela, Spain. E-mail: meffcasa{at}uscmail.usc.es

Abstract

In Cushing’s syndrome, GH secretion is blocked with all the stimuli tested. It has been reported that the acute pharmacological reduction of free fatty acids (FFA) leads to an enhancement of GH secretion in normal subjects and in pathological conditions associated with reduced GH secretion. To understand if the elevated FFA levels of hypercortisolism may be responsible for the altered GH secretion, 14 patients with active Cushing’s syndrome underwent 2 paired tests with 100 µg iv of GHRH on 2 different occasions. In one test, they were pretreated with placebo and in the other one, with acipimox 250 mg po 4 h before, and 250 mg po 1 h before GHRH. The basal FFA levels (799 ± 57 mmol/L) were reduced by acipimox throughout the whole test (values under 240 ± 28 mmol/L).

In the placebo pretreated group, GHRH-induced GH secretion was severely impeded, with a mean GH peak of 1.8 ± 0.3 µg/L and area under the curve of 121.3 ± 21.6 µg/L·120 min. All the patients showed a GHRH-mediated GH peak under 4 µg/L. Acute reduction of FFA by acipimox enhanced the GHRH action, with a mean GH peak of 11.1 ± 1.8 µg/L and area under the curve of 652.9 ± 110.3 µg/L·120 min (both P < 0.005). Individually analyzed after acipimox, all 14 subjects presented an enhancement in the GHRH-mediated GH peak, and 8 patients showed a response over 10 µg/L.

In conclusion, acute FFA reduction by acipimox increased the GH secretion elicited by GHRH in chronic hypercortisolism. Elevated FFA may be a contributing factor to the deranged GH secretion observed in Cushing’s syndrome.

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