Yuta Tezuka1,2,3, Kae Ishii2, Lili Zhao4, Yuto Yamazaki5, Ryo Morimoto3, Hironobu Sasano5, Aaron M Udager6, Fumitoshi Satoh2,3, Adina F Turcu1. 1. Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA. 2. Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8576, Japan. 3. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8576, Japan. 4. School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. 5. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8576, Japan. 6. Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
CONTEXT: Adrenocorticotropic hormone (ACTH) can contribute to aldosterone excess in primary aldosteronism (PA) via increased melanocortin type 2 receptor expression. Dynamic manipulation of the hypothalamic-pituitary-adrenal (HPA) axis could assist PA subtyping, but a direct comparison of dynamic tests is lacking. OBJECTIVE: To investigate plasma steroid differences between aldosterone-producing adenoma (APA) and bilateral PA (BPA) relative to ACTH variations. METHODS: We conducted comprehensive dynamic testing in 80 patients: 40 with APA and 40 with BPA. Peripheral plasma was collected from each patient at 6 time points: morning; midnight; after 1 mg dexamethasone suppression; and 15, 30, and 60 minutes after ACTH stimulation. We quantified 17 steroids by mass spectrometry in response to ACTH variations in all patients and compared their discriminative power between the 2 PA subtypes. RESULTS: Patients with APA had higher morning and midnight concentrations of 18-hydroxycortisol, 18-oxocortisol, aldosterone, and 18-hydroxycorticosterone than those with BPA (P < 0.001 for all). In response to cosyntropin stimulation, the APA group had larger increments of aldosterone, 18-oxocortisol, 11-deoxycorticosterone, corticosterone, and 11-deoxycortisol (P < 0.05 for all). Following dexamethasone suppression, the APA group had larger decrements of aldosterone, 18-hydroxycortisol, and 18-oxocortisol (P < 0.05 for all), but their concentrations remained higher than in the BPA group (P < 0.01 for all). The highest discriminatory performance between the PA subtypes was achieved using steroids measured 15 minutes post-ACTH stimulation (area under receiver operating characteristic curve 0.957). CONCLUSION: Steroid differences between APA and BPA are enhanced by dynamic HPA testing; such noninvasive tests could circumvent the need for adrenal vein sampling in a subset of patients with PA.
CONTEXT: Adrenocorticotropic hormone (ACTH) can contribute to aldosterone excess in primary aldosteronism (PA) via increased melanocortin type 2 receptor expression. Dynamic manipulation of the hypothalamic-pituitary-adrenal (HPA) axis could assist PA subtyping, but a direct comparison of dynamic tests is lacking. OBJECTIVE: To investigate plasma steroid differences between aldosterone-producing adenoma (APA) and bilateral PA (BPA) relative to ACTH variations. METHODS: We conducted comprehensive dynamic testing in 80 patients: 40 with APA and 40 with BPA. Peripheral plasma was collected from each patient at 6 time points: morning; midnight; after 1 mg dexamethasone suppression; and 15, 30, and 60 minutes after ACTH stimulation. We quantified 17 steroids by mass spectrometry in response to ACTH variations in all patients and compared their discriminative power between the 2 PA subtypes. RESULTS: Patients with APA had higher morning and midnight concentrations of 18-hydroxycortisol, 18-oxocortisol, aldosterone, and 18-hydroxycorticosterone than those with BPA (P < 0.001 for all). In response to cosyntropin stimulation, the APA group had larger increments of aldosterone, 18-oxocortisol, 11-deoxycorticosterone, corticosterone, and 11-deoxycortisol (P < 0.05 for all). Following dexamethasone suppression, the APA group had larger decrements of aldosterone, 18-hydroxycortisol, and 18-oxocortisol (P < 0.05 for all), but their concentrations remained higher than in the BPA group (P < 0.01 for all). The highest discriminatory performance between the PA subtypes was achieved using steroids measured 15 minutes post-ACTH stimulation (area under receiver operating characteristic curve 0.957). CONCLUSION: Steroid differences between APA and BPA are enhanced by dynamic HPA testing; such noninvasive tests could circumvent the need for adrenal vein sampling in a subset of patients with PA.
Authors: Angela Davio; Helen Woolcock; Aya T Nanba; Juilee Rege; Patrick O'Day; Jianwei Ren; Lili Zhao; Hiroki Ebina; Richard Auchus; William E Rainey; Adina F Turcu Journal: J Clin Endocrinol Metab Date: 2020-08-01 Impact factor: 5.958
Authors: Kazutaka Nanba; Kei Omata; Celso E Gomez-Sanchez; Constantine A Stratakis; Andrew P Demidowich; Mari Suzuki; Lester D R Thompson; Debbie L Cohen; James M Luther; Lan Gellert; Anand Vaidya; Justine A Barletta; Tobias Else; Thomas J Giordano; Scott A Tomlins; William E Rainey Journal: Hypertension Date: 2019-04 Impact factor: 10.190
Authors: Graeme Eisenhofer; Tanja Dekkers; Mirko Peitzsch; Anna S Dietz; Martin Bidlingmaier; Marcus Treitl; Tracy A Williams; Stefan R Bornstein; Matthias Haase; L C Rump; Holger S Willenberg; Felix Beuschlein; Jaap Deinum; Jacques W M Lenders; Martin Reincke Journal: Clin Chem Date: 2016-01-19 Impact factor: 8.327
Authors: Tracy Ann Williams; Celso E Gomez-Sanchez; William E Rainey; Thomas J Giordano; Alfred K Lam; Alison Marker; Ozgur Mete; Yuto Yamazaki; Maria Claudia Nogueira Zerbini; Felix Beuschlein; Fumitoshi Satoh; Jacopo Burrello; Holger Schneider; Jacques W M Lenders; Paolo Mulatero; Isabella Castellano; Thomas Knösel; Mauro Papotti; Wolfgang Saeger; Hironobu Sasano; Martin Reincke Journal: J Clin Endocrinol Metab Date: 2021-01-01 Impact factor: 5.958