Arginine blocks the inhibitory effect of hydrocortisone on circulating growth hormone levels in patients with acromegaly

Abstract

In patients with acromegaly, circulating growht hormone (GH) levels and GH responses to GH-releasing hormone (GHRH) are decreased by long-term administration of pharmacological doses of glucocorticoids. The aim of our study was to investigate the acute effects of intravenous (IV) infusion of hydrocortisone combined either with saline or arginine infusion on circulating GH levels in acromegaly. We studied five adult patients with acromegaly, two men and three women aged 54.6 ± 4 years having a body mass index of 25.9 ± 1.2 kg/m 2. On two randomized occasions, patients underwent a bolus IV injection of 100 mg hydrocortisone succinate at time 0 followed by a 120-minute IV infusion of 250 mg hydrocortisone in 250 mL saline, combined with a 90-minute (from −15 to 75 minutes) IV infusion of (1) 60 g arginine hydrochloride in 200 mL saline, or (2) 200 mL saline. In all of the acromegalic patients during the infusion of hydrocortisone alone, serum GH levels clearly decreased (nadir range, 26.4% to 68.1%) with respect to GH levels before hydrocortisone administration (mean of time −15 and 0, basal level), with a nadir between 90 and 180 minutes after the beginning of the infusion. After arginine pretreatment, GH levels were significantly enhanced compared with levels attained with hydrocortisone saline, and they were also significantly increased (peak, 167.5% ± 27.7%) with respect to basal levels. Our data show that arginine blocks the inhibitory effect of acute and sustained hypercortisolism on circulating GH levels in acromegaly. It also seems likely that in both acromegalic patients and 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 GH inhibition.