title: KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas.
abstract: Adrenal aldosterone-producing adenomas (APA) are rarely associated with the clear co-secretion of cortisol. Somatic mutations of the potassium channel KCNJ5 gene, with the hotspots G151R and L168R, have been recently identified in patients with APA. However, whether APAs that secrete cortisol have these mutations remains unclear. We examined three patients with APAs showing clear autonomous secretion of cortisol who possessed a 1 mg dexamethasone suppression test (DST) with a failure of the serum cortisol level to drop below 3.0 μg/dL, a morning plasma ACTH level of less than 10 pg/mL, and suppressed accumulation in the intact adrenal on (131)I- adosterol scintigraphy, or postoperative adrenal insufficiency. Laparoscopic adrenectomy revealed all tumors to be golden yellow, and histological examination confirmed them to be adrenocortical adenomas. All these patients required replacement therapy with hydrocortisone after surgery. Sequencing demonstrated that 2 of three cases showed a mutation of the KCNJ5 gene, one with c.451G>A, p.G151R and one with c.503T>G, p.L168R. Furthermore, the mRNA levels of steroidogenic enzymes including CYP11B1, CYP11B2, HSD3B2, CYP17A1, CYP11A1 and KCNJ5 in the 3 cases did not differ from those in 8 pure APAs not showing any of the above conditions for autonomous cortisol secretion. In addition, all 8 pure APAs harbored mutations of the KCNJ5 gene. These findings suggested that at least some aldosterone- and cortisol-co-secreting adrenal tumors have mutations of the KCNJ5 gene, suggesting the origin to be APA, and pure APAs may show a high incidence of KCNJ5 mutations.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan. myamada@gunma-u.ac.jp
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Sumiyasu
authors.initials: S
authors.lastname: Ishii
authors.forename: Takuya
authors.initials: T
authors.lastname: Tomaru
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ozawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibusawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshino
authors.forename: Akiko
authors.initials: A
authors.lastname: Toki
authors.forename: Emi
authors.initials: E
authors.lastname: Ishida
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D003907:Dexamethasone; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; D003907:Dexamethasone; D006854:Hydrocortisone