title: Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma.
abstract: 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.
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Ryusaku
authors: R
authors: Matsumoto
authors: Masako
authors: M
authors: Izawa
authors: Hidenori
authors: H
authors: Fukuoka
authors: Genzo
authors: G
authors: Iguchi
authors: Yukiko
authors: Y
authors: Odake
authors: Kenichi
authors: K
authors: Yoshida
authors: Hironori
authors: H
authors: Bando
authors: Kentaro
authors: K
authors: Suda
authors: Hitoshi
authors: H
authors: Nishizawa
authors: Michiko
authors: M
authors: Takahashi
authors: Naoko
authors: N
authors: Inoshita
authors: Shozo
authors: S
authors: Yamada
authors: Wataru
authors: W
authors: Ogawa
authors: Yutaka
authors: Y
authors: Takahashi
mesh_terms: D000172:Acromegaly / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002864:Chromogranins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D020022:Genetic Predisposition to Disease; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
chemical_list: D002864:Chromogranins; D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs