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Pronostic and therapeutic consequences of Gs alpha mutations in somatotroph adenomas
A Barlier1, G Gunz, A J Zamora
1Laboratoire Interactions Cellulaires Neuroendocriniennes, UMR 6544 Centre National de la Recherche Scientifique, Université de la Méditerranée, Institut Jean Roche, Faculté de Médecine Nord, Marseille, France. barlier.a@jean-roche.univ.mrs.fr
Abstract:
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 micrograms/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.
Insights
The Gs alpha (gsp) mutation in pituitary tumors predicts better response to octreotide treatment in acromegaly patients. This finding may improve management and prognosis for individuals with these tumors.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Human pituitary somatotroph adenomas are linked to G protein alpha-subunit (Gs alpha) mutations.
- The clinical impact of these gsp mutations on tumor phenotype and patient management remains unclear.
Purpose of the Study:
- To investigate the correlation between gsp mutations and tumoral phenotype in acromegaly.
- To determine if gsp mutation detection can guide patient management and predict treatment response.
Main Methods:
- Analysis of 30 acromegalic patients (8 gsp-positive, 22 gsp-negative).
- Assessment of growth hormone (GH) secretion, tumor size, and response to octreotide in vivo and in vitro.
- Postoperative follow-up of GH hypersecretion control.
Main Results:
- Gsp-positive adenomas showed significantly higher GH secretion relative to tumor size.
- Mutated adenomas exhibited superior sensitivity to octreotide, both acutely and chronically.
- Octreotide treatment effectively controlled GH hypersecretion in all gsp-positive patients, including those with residual tumor, unlike in some gsp-negative cases.
Conclusions:
- Gs alpha mutation serves as a predictive marker for somatostatin analog efficacy in acromegaly.
- Identifying gsp mutations can optimize treatment strategies and improve patient prognosis.