24 HOUR MELATONIN PATTERN IN ACROMEGALY - EFFECT OF ACUTE OCTREOTIDE ADMINISTRATION

We investigated the melatonin (MT) circadian rhythm before and after s omatostatin (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 b asal blood collection, octreotide (Sandostatin, Sandoz) 100 mu g sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-5 0 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 m easured by immunoradiometric assay in basal and after octreotide morni ng samples. The comparisons were made by Mann-U-Whitney and Wilcoxon t est as appropriate; the existence of a MT circadian rhythm was validat ed by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromeg alics had significant 24-h MT rhythm. The area under curve (AUC), meso r and amplitude of the MT rhythms in acromegalics were significantly l ower than in the controls (p<0.001, 0.002 and 0.0006, respectively), w ith an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were signif icantly increased in acromegalics in comparison with the control group . Octreotide administration significantly reduced GH, restoring a circ adian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC no t different from controls. Mean amplitude still remained lower than co ntrols (p<0.0006), with an earlier acrophase (median 00:01 h). No sign ificant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, du e especially to a blunted nocturnal increase with earlier MT peak; mor eover, acute octreotide administration increase MT levels without modi fying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secre tions or a facilitatory influence of somatostatin on daytime MT releas e 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 regulat ion of several important functions. (C) 1997, Editrice Kurtis.