Effect of acute pharmacological modulation of plasma free fatty acids on GH secretion in acromegalic patients.

OBJECTIVES

In acromegaly GH secretion is markedly increased due in most cases to a GH secreting pituitary adenoma. GH secretion is modulated by variations in the levels of free fatty acids (FFA). Recent studies in different clinical situations, have shown that reduction in FFA with acipimox (A) modifies somatotroph cell responsiveness. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on both basal GH levels and GHRH-mediated GH secretion in acromegalic patients.

PATIENTS

Six acromegalic patients (four female, two male) aged 57 +/- 4 years., with active disease due to pituitary adenomas were studied. Four of the patients had been treated previously by surgery and/or radiotherapy. The diagnosis of active acromegaly was established by clinical assessment, increased serum IGF-I and impaired GH suppression after oral glucose.

MEASUREMENTS

Four tests were performed: placebo, A (250 mg, orally, - 210 minutes and - 60 minutes), GHRH (100 microg, iv, 0 minutes) and GHRH plus A. The different tests on each subject were performed in random order one week apart, each subject served as their own control. Serum GH was measured by RIA at appropriate intervals. The area under the curve (AUC) was calculated by the trapezoidal

METHOD

Statistical analysis was performed by Wilcoxon test. P < 0.05 was considered significant.

RESULTS

The administration of A induced a FFA reduction during the entire test both when administered with placebo and with GHRH: AUC (mmol/l x 90 minutes): placebo plus placebo: 88.2 +/- 7.3. Placebo plus A: 23.2 +/- 4.6 (P < 0.05). Placebo plus GHRH: 85.4 +/- 6.9. A plus GHRH: 21.8 +/- 3.8 (P < 0.05). Mean peak GH level (microg/l) after placebo plus placebo was 5.0 +/- 1.8 not significantly different than after placebo plus A with a mean peak of 6.2 +/- 2 (P = ns). Mean peak GHRH-induced GH secretion was 26.0 +/- 15.4 and was not modified by previous A administration with mean peak of 24.4 +/- 11.8 (P = ns).

CONCLUSIONS

In acromegalic patients acute pharmacological reduction of FFA with acipimox did not modify basal GH levels or GHRH-induced GH secretion, suggesting that the adenomatous somatotroph cell is unresponsive to physiological signals such as FFA which act at a pituitary level. These data support the hypothesis of an intrinsic neoplastic pituitary defect for the pathogenesis of acromegaly.