OR20-6 Histopathology and Genetic Causes of Primary Aldosteronism in Young Patients

Abstract

Abstract Background Primary aldosteronism (PA) is the most common cause of endocrine-related hypertension. However, due to its rare incidence in younger patients, the molecular features of young-onset PA have not been well defined. Recent advances in targeted mutation analysis have identified aldosterone-driver somatic mutations in aldosterone-producing lesions including aldosterone-producing adenomas (APAs) and aldosterone-producing nodules (APNs). Objective To determine the histologic and somatic mutation profile in young-onset PA. Methods Formalin-fixed paraffin-embedded adrenals from 73 patients with unilateral PA (53 women, 19 men, and one with unknown sex) under 35 years old were analyzed. Aldosterone synthase (CYP11B2) immunohistochemistry was used to define the histopathologic classification of the aldosterone-producing lesions based on the HISTALDO consensus as well as guide DNA capture. Somatic mutations were identified by direct Sanger sequencing or Ion Torrent-based targeted next-generation sequencing. Results We identified 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPNs), and 3 non-functioning adenomas (NFAs). Of the 45 APAs and 18 APNs with successful sequencing, 43 APAs (96%) and 17 (94%) APNs harbored somatic mutations. The most frequent alterations in APAs were KCNJ5 mutations (35/45, 78%), while CACNA1D mutations were the most common in APNs (8/18, 44%). The mutation prevalence for KCNJ5 mutations did not vary between men and women. In both MAPNs, multiple CYP11B2-expressing lesions shared an identical somatic KCNJ5 mutation (c.451G>A, p.G151R). No somatic mutations were detected in the 3 NFAs. Conclusion APAs are the most common histologic feature of unilateral young-onset PA. Somatic KCNJ5 mutations are more commonly seen in APAs in both men and women, while somatic CACNA1D mutations are frequently seen in APNs in these younger patients. Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.