Effect of glucocorticoids on the paradoxical growth hormone response to thyrotropin-releasing hormone in patients with acromegaly

Abstract

It has been hypothesized that in acromegalic patients, as well as in normal subjects, acute increases in serum cortisol levels may cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid-mediated growth hormone (GH) inhibition. The aim of this study was to investigate short-term effects of an intravenous (IV) infusion of hydrocortisone on the GH response to thyrotropin-releasing hormone (TRH) in acromegaly. We studied six adult patients with active acromegaly. The group was composed of four women and two men with a mean age of 55.8 ± 6.4 years (range, 27 to 68) and a mean body mass index of 26.7 ± 1 kg/m 2 (range, 23.3 to 30). All patients underwent the following treatments: (1) hydrocortisone alone: a bolus IV injection of hydrocortisone succinate 100 mg in 2 mL saline at time −60 minutes, followed by a 120-minute IV infusion of hydrocortisone succinate 250 mg in 250 mL saline from −60 to 60 minutes; (2) TRH + hydrocortisone: a bolus IV injection of TRH 200 μg 60 minutes after initiation of a 2-hour hydrocortisone infusion; (3) TRH alone: a bolus IV injection of TRH at time 0, 60 minutes after initiation of a 2-hour saline infusion. In all six patients, TRH induced large GH increases (absolute peak GH level, 58.1 ± 23.2 μg/L; maximum % GH change with respect to baseline, 1,397.8% ± 807.8%; range, 205% to 5,219%). In the whole group of acromegalic patients, hydrocortisone infusion did not significantly affect the mean GH response to TRH (absolute peak GH level, 45.4 ± 19.5 μg/L; maximum % GH change with respect to 0-minute level, 894.8% ± 320%; range, 106% to 1,988%). After hydrocortisone + TRH administration, all six patients showed significantly higher absolute GH values as compared with values obtained with hydrocortisone alone from time 15 to 45 minutes. Our data show that the paradoxical GH response to TRH in acromegaly is resistant to the inhibitory action of an acute and sustained elevation of serum cortisol level.