cortisol-succinate--sodium-salt and Acromegaly

Hexarelin (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a GHRP-6 analog with the substitution of D-tryptophan with its 2-methyl derivative. The aim of our study was to ascertain whether hexarelin was able to counteract the glucocorticoid-mediated increase in hypothalamic somatostatin tone and consequent inhibition on serum GH levels in acromegalic patients. Ten patients (5 males, 5 females; age range 27-71 years; BMI range 23.3-35 kg/m2) with active acromegaly underwent: 1) hydrocortisone alone: a bolus iv injection of 100 mg hydrocortisone succinate in 2 mL saline, at time -60 followed by a 120 min iv infusion of 250 mg hydrocortisone succinate in 250 mL saline, from -60 to 60 min; 2) hexarelin+hydrocortisone: a bolus iv injection of hexarelin 100 micrograms, 60 min after initiation of a 2-hour hydrocortisone infusion; 3) hexarelin alone: a bolus iv injection of hexarelin at time 0, 60 min after initiation of a 2-hour saline infusion. The mean GH peak, expressed as percent change with respect to baseline level (mean of -75 and -60 minute samples), after hexarelin (1750 +/- 1157%) did not differ significantly with respect to that observed after hexarelin+hydrocortisone (1120 +/- 770%). After hydrocortisone alone the patients showed a mean decrease in GH levels as compared to baseline levels, of 47 +/- 7%. Our data show that the GH response to hexarelin in acromegaly is resistant to the inhibitor action of an acute and sustained elevation of serum cortisol levels. That hexarelin counteracts the glucocorticoid-mediated inhibition of GH secretion supports the hypothesis of an hexarelin-induced decrease in endogenous somatostatin tone.

Topics: Acromegaly; Adult; Aged; Amino Acid Sequence; Female; Growth Hormone; Growth Substances; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Molecular Sequence Data; Oligopeptides

Aim of our study was to investigate the acute effects of intravenous infusion of hydrocortisone on circulating growth hormone (GH) levels in acromegaly. We studied 5 adult patients with active acromegaly, 3 males and 2 females; age 52 +/- 3.6 years, body mass index 27 +/- 1 kg/m2. The patients underwent in randomized order from 0 to 120 min: (1) intravenous infusion of saline, 250 ml; (2) bolus intravenous injection of hydrocortisone succinate, 100 mg at time 0 followed by intravenous infusion of hydrocortisone succinate, 250 mg in 250 ml of saline for 120 min. Blood samples for GH, cortisol and glucose assay were taken at -15, 0 (time of beginning of saline or hydrocortisone infusion), 15, 30, 45, 60, 90, 120, 150 and 180 min. In all the acromegalic patients, during hydrocortisone succinate infusion, GH values clearly fell with respect to saline (nadir range 18.4-50.5% with respect to baseline levels) with nadir between 60 and 180 min after the beginning of the infusion. Our data show that acute and sustained hypercortisolism, decreases circulating GH levels in acromegaly. It seems likely that also in acromegalic patients as well as in normal subjects short-term increases in serum cortisol levels may be able to cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid-mediated GH inhibition.

Topics: Acromegaly; Adult; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Hydrocortisone; Infusions, Intravenous; Kinetics; Male; Middle Aged; Somatostatin