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Clinical characteristics of PRKACA mutations in Chinese patients with adrenal lesions: a single‐centre study
Author(s) -
Li Xintao,
Wang Baojun,
Tang Lu,
Lang Bin,
Zhang Yu,
Zhang Fan,
Chen Luyao,
Ouyang Jinzhi,
Zhang Xu
Publication year - 2016
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13134
Subject(s) - gnas complex locus , medicine , endocrinology , mutation , biology , gene , genetics
Summary Context Recent studies have identified that the somatic PRKACA L206R mutation can cause cortisol‐producing adenomas ( CPA s). This study investigated the prevalence and characteristics of PRKACA , GNAS and CTNNB 1 mutations in adrenal lesions in patients from a single centre in China. Design, Patients and Measurements We sequenced PRKACA , GNAS and CTNNB 1 genes in 108 patients, including 60 patients with CPA s (57 with unilateral and three with bilateral adenomas), 13 with nonfunctional adenomas, 12 with adrenocortical carcinomas ( ACC s), 15 with primary bilateral macronodular hyperplasia ( PBMAH ) and eight with aldosterone and cortisol cosecreting adenomas. Mutations in PRKACA , GNAS and CTNNB 1 were examined, and clinical characteristics were compared. Results Among the unilateral CPA s, we identified somatic mutations in PRKACA (L206R) in 23 cases (40·4%), GNAS (R201C and R201H) in six cases (10·5%), CTNNB 1 (S45C, L46P and S45P) in six cases (10·5%) and CTNNB 1 plus GNAS in two cases (3·5%). PRKACA and GNAS mutations were mutually exclusive. Among the patients with nonfunctional adenoma, two carried CTNNB 1 mutations. Among the patients with ACC , two carried GNAS and CTNNB 1 mutations but none carried PRKACA mutations. One patient showed bilateral CPA , and one PBMAH patient carried PRKACA mutations. No mutations in PRKACA , GNAS or CTNNB 1 were identified in the eight patients with aldosterone and cortisol cosecreting adenomas. PRKACA ‐mutant adenomas were associated with young age, overt Cushing's syndrome and high cortisol levels compared with non‐ PRKACA ‐mutant or CTNNB 1‐mutant lesions. Conclusions PRKACA mutations are present in CPA s and bilateral adrenal macronodular hyperplasia. PRKACA mutation is associated with more severe autonomous cortisol secretion.