title: Genotype-Specific Steroid Profiles Associated With Aldosterone-Producing Adenomas.
abstract: Primary aldosteronism comprises 2 main subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia. Somatic KCNJ5 mutations are found in APA at a prevalence of around 40% that drive and sustain aldosterone excess. Somatic APA mutations have been described in other genes (CACNA1D, ATP1A1, and ATP2B3) albeit at a lower frequency. Our objective was to identify genotype-specific steroid profiles in adrenal venous (AV) and peripheral venous (PV) plasma in patients with APAs. We measured the concentrations of 15 steroids in AV and PV plasma samples by liquid chromatography-tandem mass spectrometry from 79 patients with confirmed unilateral primary aldosteronism. AV sampling lateralization ratios of steroids normalized either to cortisol or to DHEA+androstenedione were also calculated. The hybrid steroid 18-oxocortisol exhibited 18- and 16-fold higher concentrations in lateralized AV and PV plasma, respectively, from APA with KCNJ5 mutations compared with all other APA combined together (P<0.001). Lateralization ratios for the KCNJ5 group were also generally higher. Strikingly, we demonstrate that a distinct steroid signature can differentiate APA genotype in AV and PV plasma. Notably, a 7-steroid fingerprint in PV plasma correctly classified 92% of the APA according to genotype. Prospective studies are necessary to translate these findings into clinical practice and determine if steroid fingerprinting could be of value to select patients with primary aldosteronism who are particularly suitable candidates for adrenal venous sampling because of a high probability of having an APA.
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.). Tracy.Williams@med.uni-muenchen.de Martin.Reincke@med.uni-muenchen.de.
authors.forename: Tracy Ann
authors.initials: TA
authors.lastname: Williams
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Mirko
authors.initials: M
authors.lastname: Peitzsch
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Anna S
authors.initials: AS
authors.lastname: Dietz
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Tanja
authors.initials: T
authors.lastname: Dekkers
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Anna
authors.initials: A
authors.lastname: Riester
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Marcus
authors.initials: M
authors.lastname: Treitl
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Yara
authors.initials: Y
authors.lastname: Rhayem
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Jaap
authors.initials: J
authors.lastname: Deinum
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.).
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.affiliation: From the Medizinische Klinik und Poliklinik IV (T.A.W., A.S.D., M.B., A.R., Y.R., F.B., M.R.) and Klinische Radiologie (M.T.), Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy (T.A.W.); Institute of Clinical Chemistry and Laboratory Medicine (M.P., G.E.) and Department of Internal Medicine III (J.W.M.L., G.E.), Technische Universtät Dresden, Dresden, Germany; and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands (T.D., J.W.M.L., J.D.). Tracy.Williams@med.uni-muenchen.de Martin.Reincke@med.uni-muenchen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000235:genetics; D018246:Adrenocortical Adenoma / Q000097:blood* / Q000235:genetics; D000450:Aldosterone / Q000378:metabolism*; D002853:Chromatography, Liquid; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D004273:DNA, Neoplasm; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D006854:Hydrocortisone
keywords: adrenal glands; aldosterone; hyperaldosteronism; liquid chromatography; tandem mass spectrometry