title: Measurement of peripheral plasma 18-oxocortisol can discriminate unilateral adenoma from bilateral diseases in patients with primary aldosteronism.
abstract: Adrenal venous sampling is currently the only reliable method to distinguish unilateral from bilateral diseases in primary aldosteronism. In this study, we attempted to determine whether peripheral plasma levels of 18-oxocortisol (18oxoF) and 18-hydroxycortisol could contribute to the clinical differentiation between aldosteronoma and bilateral hyperaldosteronism in 234 patients with primary aldosteronism, including computed tomography (CT)-detectable aldosteronoma (n=113) and bilateral hyperaldosteronism (n=121), all of whom underwent CT and adrenal venous sampling. All aldosteronomas were surgically resected and the accuracy of diagnosis was clinically and histopathologically confirmed. 18oxoF and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry. Receiver operating characteristic analysis of 18oxoF discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cut-off value of 4.7 ng/dL, compared with that based on 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96). 18oxoF levels above 6.1 ng/dL or of aldosterone >32.7 ng/dL were found in 95 of 113 patients with aldosteronoma (84%) but in none of 121 bilateral hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning nodules in their adrenals. In addition, 18oxoF levels below 1.2 ng/dL, the lowest in aldosteronoma, were found 52 of the 121 (43%) patients with bilateral hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro aldosteronomas revealed that 8 of these 27 patients had CT-detectable contralateral adrenal nodules, the highest values of 18oxoF and aldosterone were 4.8 and 24.5 ng/dL, respectively, both below their cut-off levels indicated above. The peripheral plasma 18oxoF concentrations served not only to differentiate aldosteronoma but also could serve to avoid unnecessary surgery for nonfunctioning adrenocortical nodules concurrent with hyperplasia or microadenoma.
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.). fsatoh@mail.tains.tohoku.ac.jp.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Ono
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Kei
authors.initials: K
authors.lastname: Omata
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Masataka
authors.initials: M
authors.lastname: Kudo
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Kei
authors.initials: K
authors.lastname: Takase
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Seiji
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Sasamoto
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Seijiro
authors.initials: S
authors.lastname: Honma
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Okuyama
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Kouwa
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: From the Division of Nephrology, Endocrinology, and Vascular Medicine, Departments of Medicine (F.S., R.M., Y.O., Y.I., K.O., M.K., S.I.), Radiology (K.T., K.S.), Urology (Y.A.), and Pathology (H.S., Y.N.), Tohoku University Hospital, Sendai, Japan; Aska Pharma Medical Co Ltd, Kawasaki, Japan (H.S., S.H., M.O.); Division of Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, Sendai, Japan (K.Y.); Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.); and Molecular and Integrative Physiology, University of Michigan, Ann Arbor (W.E.R.).
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis*; D000450:Aldosterone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000097:blood; D006929:Hyperaldosteronism / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; C038135:18-oxocortisol; D000450:Aldosterone; C033689:18-hydroxycortisol; D006854:Hydrocortisone
keywords: 1-(2-(18F)fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo-isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole; hyperaldosteronism