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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 5 1604-1610
Copyright © 1998 by The Endocrine Society

Original Studies

Pronostic and Therapeutic Consequences of Gs{alpha} Mutations in Somatotroph Adenomas1

Anne Barlier, Ginette Gunz, Alfredo J. Zamora, Isabelle Morange-Ramos, Dominique Figarella-Branger, Henri Dufour, Alain Enjalbert and Philippe Jaquet

Laboratoire Interactions Cellulaires Neuroendocriniennes, UMR 6544 Centre National de la Recherche Scientifique, Université de la Méditerranée, Institut Jean Roche, Faculté de Médecine Nord (A.B., G.G., A.J.Z., I.M.-R., A.E., P.J.); and Service d’Endocrinologie (I.M.-R., P.J.), Laboratoire d’Anatomie-Pathologique et de Neuropathologie (D.F.-B.), and Service de Neurochirurgie (H.D.), Centre Hospitalo-Universitaire Timone, Marseille, France

Address all correspondence and requests for reprints to: Dr. Anne Barlier, Laboratoire ICNE, UMR 6544 CNRS, Université de la Méditerranée, Institut Fédératif Jean-Roche, Faculté de Médecine Nord, boulevard P. Dramard, 13916 Marseille Cedex 20, France. E-mail: barlier.a{at}jean-roche.univ.mrs.fr

Human pituitary somatotroph adenomas can be associated with mutations of the s{alpha}-subunit of G proteins. However, the impact of the gsp mutations on the tumoral phenotype is not well understood at present. This study aims to determine whether the detection of this mutation could impact on the management of acromegalic patients. We examined 30 acromegalic patients; 8 were gsp positive, and 22 were gsp negative. The gsp-positive adenomas appeared to secrete significantly more when the ratio of basal GH level/tumor size was considered. A better octreotide sensitivity of mutated adenomas was clearly shown under in vivo (short and long term) and in vitro conditions. During the acute octreotide test, the GH nadir was significantly lower in the gsp-positive adenomas (85% of maximal inhibition vs. 52%). Eighteen patients were treated with octreotide (300 µg/day) for at least 3 months before surgery: the percent inhibition of GH hypersecretion was higher in gsp-positive adenomas (76% vs. 47%). In cell culture, the octreotide-induced inhibition of GH release was significantly higher in gsp-positive adenomas (71% vs. 30%). Finally, during 2 yr of postoperative follow-up, GH hypersecretion was controlled in all patients with gsp mutation even in those in whom tumoral tissue remained after surgery. On the contrary, in the gsp-negative group, octreotide treatment was unable to control hypersecretion in 4 patients bearing tumoral remnants. The Gs{alpha} mutation could, therefore, be a new marker to foresee the susceptibility of the tumor to be controlled by somatostatin analogs, which improves prognosis.




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