Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma

Endocrine journal

Wataru Ogawa¹  Shozo Yamada²  Masako Izawa³  Kenichi Yoshida⁴  Kentaro Suda⁴  Michiko Takahashi⁴  Hironori Bando⁴  Hitoshi Nishizawa⁴  Yutaka Takahashi⁴  Naoko Inoshita⁴  Ryusaku Matsumoto⁴  Genzo Iguchi⁵  Yukiko Odake⁵  Hidenori Fukuoka⁶ 

[1] Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan;Department of Pathology, Toranomon Hospital, Tokyo, Japan;Department of Pediatric Endocrinology and Metabolism, Aichi Children’Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan;Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan;s Health and Medical Center, Obu, Japan

关键词: Acromegaly;    Gigantism;    GNAS;    AIP;    GPR101;   

DOI  :  10.1507/endocrj.EJ16-0075

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported.To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history.Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%).No patients had G protein-coupled receptor 101 (GPR101) mutations.The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics.The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test.In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed.One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled.The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective.These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained.In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations.

【 授权许可】

Unknown