Graeme Eisenhofer1, Tanja Dekkers2, Mirko Peitzsch3, Anna S Dietz4, Martin Bidlingmaier4, Marcus Treitl5, Tracy A Williams6, Stefan R Bornstein7, Matthias Haase8, L C Rump9, Holger S Willenberg10, Felix Beuschlein4, Jaap Deinum2, Jacques W M Lenders11, Martin Reincke4. 1. Institute of Clinical Chemistry and Laboratory Medicine and Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany; graeme.eisenhofer@uniklinikum-dresden.de. 2. Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 3. Institute of Clinical Chemistry and Laboratory Medicine and. 4. Medizinische Klinik und Poliklinik IV and. 5. Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany; 6. Medizinische Klinik und Poliklinik IV and Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy; 7. Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany; 8. Department of Endocrinology, Diabetes, and Metabolism and. 9. Department of Nephrology, University Dusseldorf, Medical Faculty, Dusseldorf, Germany; and. 10. Department of Endocrinology, Diabetes, and Metabolism and Division of Endocrinology and Metabolism, Rostock University Medical Center, Rostock, Germany. 11. Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany; Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
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.
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: Lina Schiffer; Lise Barnard; Elizabeth S Baranowski; Lorna C Gilligan; Angela E Taylor; Wiebke Arlt; Cedric H L Shackleton; Karl-Heinz Storbeck Journal: J Steroid Biochem Mol Biol Date: 2019-07-27 Impact factor: 4.292
Authors: Finn Holler; Daniel A Heinrich; Christian Adolf; Benjamin Lechner; Martin Bidlingmaier; Graeme Eisenhofer; Tracy Ann Williams; Martin Reincke Journal: Curr Hypertens Rep Date: 2019-09-03 Impact factor: 5.369
Authors: Naris Nilubol; Steven J Soldin; Dhaval Patel; Muthoni Rwenji; Jianghong Gu; Likhona S Masika; Richard Chang; Constantine A Stratakis; Electron Kebebew Journal: Int J Endocr Oncol Date: 2017-04-27
Authors: Juilee Rege; Aya T Nanba; Richard J Auchus; Jianwei Ren; Hwei-Ming Peng; William E Rainey; Adina F Turcu Journal: J Clin Endocrinol Metab Date: 2018-01-01 Impact factor: 5.958
Authors: Fady Hannah-Shmouni; Annabel Berthon; Fabio R Faucz; Juan Medina Briceno; Andrea Gutierrez Maria; Andrew Demidowich; Mirko Peitzsch; Jimmy Masjkur; Fidéline Bonnet-Serrano; Anna Vaczlavik; Jérôme Bertherat; Martin Reincke; Graeme Eisenhofer; Constantine A Stratakis Journal: Endocr Relat Cancer Date: 2020-07 Impact factor: 5.678
Authors: Jacques W M Lenders; Tracy Ann Williams; Martin Reincke; Celso E Gomez-Sanchez Journal: Eur J Endocrinol Date: 2017-09-13 Impact factor: 6.664