Maurizio Schettino

Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease.

Subjects with Cushings disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushings disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushings disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushings disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushings disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushings disease.

Effect of galanin on the growth hormone response to growth hormone-releasing hormone in acromegaly.

Galanin enhances growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in normal man. In acromegaly, circulating GH levels are increased and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in acromegalic subjects. Five acromegalic patients (three men and two women) and seven healthy adult subjects (five men and two women) were studied. GHRH-induced GH secretion was evaluated during a 40-minute intravenous (IV) infusion of saline (100 mL) or porcine galanin (12.5 micrograms/min in 100 mL saline). In normal subjects, delta GH levels after GHRH+porcine galanin administration (47 +/- 7.5 micrograms/L) were significantly higher in comparison to levels obtained with GHRH+saline (21.7 +/- 3.5 micrograms/L, P < .05). In acromegalic patients, GH responses to GHRH (delta GH, 18.8 +/- 8.6 micrograms/L) were not altered by galanin infusion (delta GH, 17.6 +/- 5 micrograms/L). Our results give the first evidence that the same dose of galanin that induces a significant enhancement of the GH response to GHRH in normal subjects has no effect on the GH response to GHRH in acromegalic patients. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by somatotropes independent of GHRH. Failure of galanin to enhance GH response to GHRH in acromegalic patients could be due to a change in function of the galanin receptor on GH-secreting adenomatous cells.

Acute Effects of Hydrocortisone on Circulating Growth Hormone Levels in Patients with Acromegaly

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.