Context: Due to its rare incidence, molecular features of primary aldosteronism (PA) in young adults are largely unknown. Recently developed targeted mutational analysis identified aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters. Objective: To investigate histologic and genetic characteristics of lateralized PA in young adults. Methods: Formalin-fixed, paraffin-embedded adrenal tissue sections from 74 young patients with lateralized PA (<35 years old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to define the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing. Results: Based on the CYP11B2 IHC results, histopathologic classification was made as follows: 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPN), 1 double APN, 1 APA with MAPN, and 2 nonfunctioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identified in NFAs. Conclusion: APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population.
|Number of pages||10|
|Journal||Journal of Clinical Endocrinology and Metabolism|
|Publication status||Published - 2022 Sept 1|
Bibliographical noteFunding Information:
This work was supported by grants from American Heart Association (17SDG33660447 to K. Nanba), the Humboldt Foundation (W.E. Rainey), the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (DK106618 and DK043140 to W.E. Rainey), National Center for Advancing Translational Sciences (KL2TR001879 to H. Wachtel), and National Heart, Lung and Blood institute (R01HL130106 to T. Else.).
© 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical