EFFECT OF CORTICOTROPIN-RELEASING HORMONE ADMINISTRATION ON GROWTH-HORMONE LEVELS IN ACROMEGALY - IN-VIVO AND IN-VITRO STUDIES

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 mu g sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mu mol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factor levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study. No significant GH increase was found in the CRH non-responders and in the three CRH responders in whom the GH paradoxical response to CRH disappeared during octreotide treatment. Conversely, a significant GH increase (over 250% of pre-incubation values) after CRH administration was found in the remaining case. In conclusion, the results of the present study show that CRH is rarely able to stimulate paradoxical GH response in patients with active acromegaly and that the in vivo recorded GH release after CRH is in vitro reproducible only in extremely rare cases.