PERSISTENCE OF SOMATOSTATINERGIC TONE IN ACROMEGALY

It is a matter of debate whether hypothalamic somatostatin (SRIH) secr etion in acromegaly is preserved and still regulated by the physiologi cal feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH ) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasion s (r = 0.99, p < 0.001). The test was performed also before and after the administration of drugs able to inhibit or stimulate hypothalamic SRIH release, by activating (pyridostigmine) or inhibiting (pirenzepin e) cholinergic pathways, respectively. The GHRH-induced GH response (P /B = 2, range 1.1-26.1) was increased significantly by pyridostigmine pretreatment in 30 patients (P/B = 2.6, range 1.3-34.8; p = 0.0045). I n nine out of 30 patients an increase of greater than 2 SD of within-s ubject GHRH variability was observed in response to GHRH plus pyridost igmine when compared to GHRH alone. An inverse correlation (r = -0.37, p < 0.05) was observed between GH response to GHRH alone and after py ridostigmine pretreatment. On the contrary, no change of GHRH-induced GH response was observed in 12 patients after pirenzepine pretreatment (P/B = 1.9, range 1.1-5 and P/B = 2, range 1.3-6 without and after pi renzepine pretreatment, respectively). These data suggest that in acro megaly the somatostatinergic tone does not seem to fluctuate, and that it can be inhibited often by cholinergic pathway activation but not i ncreased further by cholinergic suppression.