title: Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism.
abstract: A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m2). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH <1.0 pg/mL, and cortisol 21.6 μg/dL. Liquid chromatography-tandem mass spectrometry analysis showed that aldosterone (104 times the control) as well as its precursors were significantly elevated in the patient's plasma. A left adrenal (4-cm-diameter) tumor with 131I-Adosterol uptake was found and removed. Four days later, plasma aldosterone and renin activity had dropped to 7.73 ng/dL and 1.6 ng/mL/hr, respectively. However, they rose to 24.0 ng/dL and 10.9 ng/mL/hr, respectively, by Day 102. Nevertheless, magnetic resonance angiography found no evidence of a renovascular lesion. The tumor was a benign adrenocortical adenoma composed predominantly of clear cells positive for 17α-hydroxylase, [hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerases], and aldosterone synthase. A quantitative real-time polymerase chain reaction analysis of the tumor cells revealed that expression of the gene encoding aldosterone synthase was 85 times the control level. In addition, the tumor cells harbored G151R mutation of the inward rectifying potassium channel subfamily j, member 5 gene. The striking overexpression of aldosterone synthase by the tumor cells was considered the primary mechanism for the extravagant overproduction of aldosterone in this case. This overexpression may have resulted from integration of signals from AII and forced membrane depolarization due to the potassium channel mutation.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okubo
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Nakasone
authors.forename: Katsuko
authors.initials: K
authors.lastname: Shirotori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Oguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Komatsu
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Toru
authors.initials: T
authors.lastname: Aizawa
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000150:complications; D018246:Adrenocortical Adenoma / Q000097:blood / Q000150:complications; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood* / Q000209:etiology; D008297:Male; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000450:Aldosterone