Twenty-four hour melatonin pattern in acromegaly: effect of acute octreotide administration

Abstract

We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p < 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p < 0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions.