PRONOSTIC AND THERAPEUTIC CONSEQUENCES OF G(S)ALPHA MUTATIONS IN SOMATOTROPH ADENOMAS

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 c ould impact on the management of acromegalic patients. We examined 30 acromegalic patients; 8 were gsp positive, and 22 were gsp negative. T he gsp-positive adenomas appeared to secrete significantly more when t he ratio of basal GH level/tumor size was considered. A better octreot ide sensitivity of mutated adenomas was clearly shown under in vivo (s hort and long term) and in vitro conditions. During the acute octreoti de test, the GH nadir was significantly lower in the gsp-positive aden omas (85% of maximal inhibition us. 52%). Eighteen patients were treat ed with octreotide (300 mu g/day) for at least 3 months before surgery : the percent inhibition of GPI hypersecretion was higher in gsp-posit ive adenomas (76% vs. 47%). In cell culture, the octreotide-induced in hibition of GH release was significantly higher in gsp-positive adenom as (71% vs. 30%). Finally, during 2 yr of postoperative follow-up, GH hypersecretion was controlled in all patients with gsp mutation even i n those in whom tumoral tissue remained after surgery. On the contrary , in the gsp-negative group, octreotide treatment was unable to contro l hypersecretion in 4 patients bearing tumoral remnants. The G(s) alph a mutation could, therefore, be a new marker to foresee the susceptibi lity of the tumor to be controlled by somatostatin analogs, which impr oves prognosis.