Effect of Opiates on Growth Hormone Secretion in Acromegaly

Abstract

Morphine at doses of 5 mg and 10 mg does not stimulate growth hormone (GH) secretion in normal subjects, and its effect on GH secretion in acromegaly is not widely documented. We investigated the effect of 15 mg intravenous morphine on growth hormone in patients with active acromegaly compared to normal subjects (7 acromegalics and 5 controls). Their mean (+/- SEM) age was 30.5 +/- 7.6 years and 29.5 +/- 0.5 years, respectively. Basal and peak response of growth hormone after morphine was measured with simultaneous assay of cortisol to exclude the effect of stress. Mean (+/- SEM) basal growth hormone was 103.16 +/- 28.04 ng/ml in acromegalics compared to 4.51 +/- 1.43 ng/ml in controls. Morphine caused an elevation of growth hormone in both acromegalics and normal subjects (p < 0.05). However, the Delta (peak minus basal) response of growth hormone was comparable between the two groups. A concurrent fall in cortisol was noted after morphine in both the groups, excluding the effect of stress on growth hormone. We conclude that higher doses (15 mg) of morphine are required to stimulate GH secretion in normal subjects, and that opioids exert a positive modulating effect on growth hormone secretion in patients with active acromegaly suggesting partial autonomy of the pituitary tumor.

MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids

“…Continuous morphine exposure of male rats resulted in increased basal and mean GH concentrations, as well as in a modest increase of the GH pulse frequency but not of pulse amplitude; in females, morphine, apart from a marked reduction in the pulse amplitude, had little effect on other parameters of GH secretion (91). In human subjects, there are acute stimulatory effects of opioids on GH secretion which relate with the dose offered (92,93). Thus, intravenous morphine at doses of 5 mg and 10 mg did not promote GH secretion but a higher dose of 15 mg did (92,94,95).…”

“…In human subjects, there are acute stimulatory effects of opioids on GH secretion which relate with the dose offered (92,93). Thus, intravenous morphine at doses of 5 mg and 10 mg did not promote GH secretion but a higher dose of 15 mg did (92,94,95). Notably, administration of a Met-enkephalin analogue G-DAMME, in healthy men combined with a maximally stimulatory dose of a GHRH analogue resulted to an enhancing effect of the GHRHinduced GH release, suggesting that other mechanisms are also implicated (93).…”

Effect of the co-administration of glucose with morphine on glucoregulatory hormones and causing of diabetes mellitus in rats

“…[ 30 31 ] The increased serum leptin level decreases insulin sensitivity in some tissues, and the function of pancreatic beta-cells becomes deficient[ 32 ] and hyperinsulinism occurs. [ 31 33 ] On the contrary, Ferenczi et al . reported that the insulin plasma level was lower in morphine user with respect to normal group.…”

Opioid-induced endocrinopathies

“…86 Acute administration of opioids in healthy humans has a dose-related stimulatory effect on GH production; intravenous administration of 15 mg morphine stimulated GH secretion, whilst smaller doses (5 and 10 mg) had no effect. [87][88][89] Studies on the impact of chronic opioid administration have shown conflicting results. Serum insulin-like growth factor 1 (IGF-1) levels were significantly lower in humans on intrathecal opioids (morphine and hydromorphone) for non-malignant pain compared to controls, with 15% (9/62) of the cases demonstrating suboptimal response to ITT (peak GH values <3 μg/L) and 17% (12/72) having IGF-1 concentrations more than two standard deviations below the mean.…”