title: Evaluation of GH paradoxical responses to TRH and LHRH in acromegalic patients during long-term treatment with octreotide.
abstract: In some acromegalics, GH release can be induced by TRH and/or LHRH administration. The pathogenesis of these GH paradoxical responses was supposed to be a somatotroph-reduced sensitivity to somatostatin, somatotrophin release-inhibiting factor (SRIF), or an hypothalamic derangement of the SRIF release. In this study, this hypothesis was investigated by means of GH suppression during chronic therapy with octreotide [Somatostatin analogue (SMS)] in order to evaluate the possible correlation between GH and insulin-like growth factor 1 (IGF-1) normalization and the disappearance of these paradoxical responses in 15 acromegalic patients: 15/15 with a paradoxical GH rise after TRH and 7/15 with a paradoxical GH rise after LHRH. SMS therapy was administered subcutaneously at the dose of 150-450 micrograms/day. During the treatment, GH and IGF-1 levels normalized in 12 patients and were reduced in the remaining 3 others. The GH response to TRH disappeared in 7 patients, while the GH response to LHRH disappeared in 4 patients. chi 2 analysis failed to show any significant correlation between GH and IGF-1 normalization and the disappearance of GH response to TRH and LHRH (chi 2 = 0.00686). No linear correlation existed between GH/IGF-1 decrease and GH peak or area under the curve at any time ('r' values: TRH test, GH -0.47, IGF-1 -0.48; LHRH test, GH -0.50, IGF-1 -0.49). The absence of any significant correlation between GH/IGF-1 normalization and the disappearance of GH paradoxical responses during chronic octreotide administration suggests that other factors apart from SRIF sensitivity are involved in the genesis of these responses.
authors.affiliation: Chairs of Endocrinology, University of Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Merola
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: M
authors.initials: M
authors.lastname: Cataldi
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Selleri
authors.forename: F
authors.initials: F
authors.lastname: Briganti
authors.forename: G
authors.initials: G
authors.lastname: Schettini
authors.forename: A
authors.initials: A
authors.lastname: Bellastella
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D005260:Female; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D013973:Thyrotropin-Releasing Hormone
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide