Characteristics of gsp-Positive Growth Hormone-secreting Pituitary Tumors

Park, Bong Jin; Kim, Gook Ki; Lim, Young Jin; Kim, Tae Sung; Rhee, Bong Arm; Leem, Won; Yang, In Myung; Choi, Young Kil

Abstract

A subset of human growth hormone(GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the alpha subunit of Gsalpha, a stimulatory GTP-binding protein. The purpose of this study was to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical reaction of these patients to endocrine testing. Direct PCR sequencing revealed gsp oncogene mutation in nine of 21 tumors(43%) at amino acid 201 of the Gsalpha protein. A single nucleotide mutation in tumors carrying the gsp oncogene was observed in eight tumors, this replaced an arginine(CGT) in normal protein with cysteine(TGT), and in one, with serine(AGT). Patients in the in whom gsp oncogene mutation occurred were older(54 years vs. 41 years, p=0.01) than those in the normal group. Sex, tumor grade, basal GH and PRL levels, GH response to oral glucose loading, GH fluctuation, and paradoxical response to TRH or GnRH did not differ between the groups : gsp oncogene was found mostly in somatotroph adenomas. Octreotide-induced GH suppression was significantly higher in the mutation group than in the normal group(95% vs. 81%, p=0.03), but the GH response to bromocriptine did not differ between the groups. These results suggest that Gsalpha mutations of GH-secreting tumors occur in Korean acromegalic patients with a similar frequency to that found in Western countries. Patients with gsp oncogene are likely to be older than those without it, and show high levels of octreotide-induced GH suppression.