학술논문
Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study.
Document Type
Academic Journal
Author
Turcu AF; Division of Metabolism, Endocrinology, and Diabetes (A.F.T., Z.S., H.L.), University of Michigan, Ann Arbor.; Tezuka Y; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (Y.T., F.S.).; Lim JS; Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, South Korea (J.S.L.).; Salman Z; Division of Metabolism, Endocrinology, and Diabetes (A.F.T., Z.S., H.L.), University of Michigan, Ann Arbor.; Sehgal K; Department of Medicine, Centre for Endocrinology and Metabolism (K.S., J.Z., J.Y.), Hudson Institute of Medical Research, Clayton, VIC, Australia.; Liu H; Division of Metabolism, Endocrinology, and Diabetes (A.F.T., Z.S., H.L.), University of Michigan, Ann Arbor.; Larose S; Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l'Université de Montréal, Québec, Canada (S.L., A.L.).; Parksook WW; Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (W.W.P., A.V.).; Williams TA; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany (T.A.W., M.R.).; Cohen DL; Renal-Electrolyte and Hypertension Division (D.L.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Wachtel H; Department of Surgery (H.W.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.; Zhang J; Department of Medicine, Centre for Endocrinology and Metabolism (K.S., J.Z., J.Y.), Hudson Institute of Medical Research, Clayton, VIC, Australia.; Dorwal P; Department of Pathology (P.D.), Hudson Institute of Medical Research, Clayton, VIC, Australia.; Satoh F; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (Y.T., F.S.).; Yang J; Department of Medicine, Centre for Endocrinology and Metabolism (K.S., J.Z., J.Y.), Hudson Institute of Medical Research, Clayton, VIC, Australia.; Lacroix A; Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l'Université de Montréal, Québec, Canada (S.L., A.L.).; Reincke M; Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Germany (T.A.W., M.R.).; Giordano TJ; Department of Pathology (T.J.G., A.M.U.), University of Michigan, Ann Arbor.; Udager AM; Department of Pathology (T.J.G., A.M.U.), University of Michigan, Ann Arbor.; Vaidya A; Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (W.W.P., A.V.).; Rainey WE; Department of Molecular and Integrative Physiology (W.E.R.), University of Michigan, Ann Arbor.
Source
Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy.
Methods: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue.
Results: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]).
Conclusions: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.
Competing Interests: Disclosures J. Yang has received project support from DiaSorin Pty Ltd and is supported by a Fellowship from the National Health and Medical Research Council of Australia. A. Vaidya reports consulting fees unrelated to the contents of this work from Corcept Therapeutics, Mineralys, HRA Pharma. A.F. Turcu served as local investigator in a clinical trial conducted by CinCor/AstraZeneca. All other authors declare no conflict of interest.
Methods: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue.
Results: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]).
Conclusions: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.
Competing Interests: Disclosures J. Yang has received project support from DiaSorin Pty Ltd and is supported by a Fellowship from the National Health and Medical Research Council of Australia. A. Vaidya reports consulting fees unrelated to the contents of this work from Corcept Therapeutics, Mineralys, HRA Pharma. A.F. Turcu served as local investigator in a clinical trial conducted by CinCor/AstraZeneca. All other authors declare no conflict of interest.