7312 Tumor Size and Mutation Prevalence in Black Americans with Primary Aldosteronism

Abstract Disclosure: D. van Rooyen: None. K. Nanba: Other; Self; AstraZeneca. D.R. Sapiro: None. A. Blinder: None. H. Wachtel: None. D. Cohen: None. J.M. Luther: Advisory Board Member; Self; consulted with Mineralys. A. Vaidya: None. T.J. Giordano: None. A. Turcu: None. A. Udager: None. W.E. Rainey: None. J. Rege: None. Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension. The prevalence of aldosterone-driver somatic mutations varies with sex and race. KCNJ5 mutations are commonly found in White Americans and female patients with PA. In contrast, CACNA1D mutations are dominant in Black American PA patients, but existing data are limited to small cohorts. Objective: To determine the impact of tumor size on aldosterone-driver mutation prevalence in Black Americans with PA. Methods: 113 formalin-fixed, paraffin-embedded adrenal tumors from Black American patients with PA were included. Histological classification was made based on aldosterone synthase (CYP11B2) immunohistochemistry and tumor diameter: aldosterone-producing adenomas (APA), ≥10 mm and aldosterone-producing nodules (APN), ≥3 - 10 mm. Somatic mutations in CYP11B2-positive regions were analyzed using Sanger- and next generation sequencing. Results: Most aldosterone-driver somatic mutations in Black American tumors were seen in CACNA1D (48/113, 42%) followed by KCNJ5 (34%), ATP1A1 (11%), ATP2B3 (4%), and CADM1 (1%). 9% of tumors did not exhibit known mutations (mutation-negative; Mneg). Importantly, there was a correlation between mutation prevalence and tumor size. Adrenals from this Black American PA cohort exhibited APN in 59% (67/113) of patients, most of which harbored somatic mutations in CACNA1D (44/67, 66%), followed by ATP1A1 (12%), Mneg (10%), and KCNJ5 (7%). In contrast, most APAs (n=46) displayed mutations in KCNJ5 (33/46, 72%), and a lower detection rate for mutations in CACNA1D, ATP1A1, ATP2B3, and for Mneg samples (28%, collectively). Irrespective of size, KCNJ5 mutations were observed more frequently in tumors from females (50%; n=62) vs males (14%; n=51). However, CACNA1D was the dominant altered gene in APN, regardless of sex. Conclusion: Aldosterone-producing tumor size exhibited a higher correlation with mutation prevalence than sex. Smaller APN are the dominant histologic feature in Black Americans with PA, and most of these lesions harbor somatic CACNA1D mutations. In contrast, somatic KCNJ5 mutations are more common in APA, and particularly in women. Future studies are needed to determine if the combination of adrenal imaging and genotype-specific steroid profiles could assist with PA subtyping. Presentation: 6/3/2024