title: Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism.
abstract: BACKGROUND
  Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS-based steroid profiling to stratify patients with primary aldosteronism.
  
  
  METHODS
  Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with primary aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios.
  
  
  RESULTS
  Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS-derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P < 0.0001) than immunoassay-derived ratios. The hybrid steroids, 18-oxocortisol and 18-hydroxycortisol, also showed lateralized secretion in 76% and 35% of patients with APAs. Adrenal venous concentrations of glucocorticoids and androgens were bilaterally higher in patients with BAH than in those with APAs. Consequently, peripheral plasma concentrations of 18-oxocortisol were 8.5-fold higher, whereas concentrations of cortisol, corticosterone, and dehydroepiandrosterone were lower in patients with APAs than in those with BAH. Correct classification of 80% of cases of APAs vs BAH was thereby possible by use of a combination of steroids in peripheral plasma.
  
  
  CONCLUSIONS
  LC-MS/MS-based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine and Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany; graeme.eisenhofer@uniklinikum-dresden.de.
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.affiliation: Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Tanja
authors.initials: T
authors.lastname: Dekkers
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine and.
authors.forename: Mirko
authors.initials: M
authors.lastname: Peitzsch
authors.affiliation: Medizinische Klinik und Poliklinik IV and.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Dietz
authors.affiliation: Medizinische Klinik und Poliklinik IV and.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Marcus
authors.initials: M
authors.lastname: Treitl
authors.affiliation: Medizinische Klinik und Poliklinik IV and Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy;
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Williams
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany;
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Haase
authors.affiliation: Department of Nephrology, University Dusseldorf, Medical Faculty, Dusseldorf, Germany; and.
authors.forename: L C
authors.initials: LC
authors.lastname: Rump
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism and Division of Endocrinology and Metabolism, Rostock University Medical Center, Rostock, Germany.
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.affiliation: Medizinische Klinik und Poliklinik IV and.
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Jaap
authors.initials: J
authors.lastname: Deinum
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany; Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.affiliation: Medizinische Klinik und Poliklinik IV and.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
mesh_terms: D000236:Adenoma / Q000378:metabolism; D002853:Chromatography, Liquid; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood / Q000175:diagnosis*; D013058:Mass Spectrometry; D013256:Steroids / Q000097:blood*
chemical_list: D013256:Steroids