Effect of corticotrophin-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 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 micrograms sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mumol/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-I 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Colao
A
A
Dipartimento di Endocrinologia ed Oncologia Clinica e Molecolare, Università Federico II Facoltà di Medicina e Chirurgia, Napoli, Italy.
Merola
B
B
Ferone
D
D
Calabrese
M R
MR
Longobardi
S
S
Spaziante
R
R
Di Renzo
G
G
Annunziato
L
L
Lombardi
G
G
D000172:Acromegaly / Q000097:blood* / Q000209:etiology; D000236:Adenoma / Q000150:complications / Q000188:drug therapy; D000328:Adult; D000704:Analysis of Variance; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy; D011863:Radioimmunoassay; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D015282:Octreotide