Endocrine Abstracts (2019) 65 P281 | DOI: 10.1530/endoabs.65.P281

Clinical PhenClinical phenotypes of GNAS gene mutations in Korean Acromegalic Patientsotypes of GNAS gene mutations in Korean acromegalic patients

Cheol Ryong Ku1,2, Hyein Jung1, Kyungwon Kim1, Daham Kim1 & Eun Jig Lee1,2


1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Severance Hospital Pituitary Tumor Center, Seoul, Republic of Korea


Background: Guanine nucleotide-binding protein, α stimulating (GNAS) gene have been reported to be associated with GH secreting pituitary adenoma. Approximately 40% of patients with acromegaly have GNAS mutation. In this study, we investigated the prevalence of GNAS mutation in Korean acromegalic patients and assessed the correlation with the biochemical or clinical characteristics.

Method: We studied acromegalic patients who underwent surgery between from July 2005 to January 2017 in Severance Hospital. GNAS gene analysis was performed with amplications of regions containing hotspot 2 sites of activating somatic mutations in codons 201 and 227. We evaluated the age, gender, GH, IGF-1 levels, postoperative biochemical remissions and immunohistochemical staining results of tumor.

Result: GNAS mutations were present in 75 of the 126 acromegalic pateints (59.5%). Among the GNAS mutant patient, 61 subjects (81%) had mutation in codon 201. There was no difference in age distribution and Hardy classification according to GNAS mutation. Female proportion was 76.5% and 48.0% in GNAS wild type and mutant group, respectively (P=0.006). GNAS mutant group had higher prevalence of overall GH expression in immunohistochemical staining (98.7% vs. 92.2%, P = 0.015). Furthermore, they had higher IGF-1 level preoperatively (791.3 vs. 697.0 ng/ml, P=0.045). Immediate postoperative nadir GH (0.3 vs. 0.6 ng/ml, P=0.012) in oral glucose tolerance test (OGTT) was lower in GNAS mutant patients. Surgical remission rates were significantly higher in GNAS mutant patients, evaluated both at immediately and at 6 months after operation (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).

Conclusion: In conclusion, GNAS mutation was more frequently found in Korean acromegalic patients. GNAS mutation positive tumors tended to have higher preoperative IGF-1 level, surgical remission rate and lower immediate postoperative nadir GH on OGTT. Identifying the GNAS mutation would be helpful in predicting patient’s clinical features and prognosis.

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