Cardiovascular Endocrinology

ORF31-07 - Somatic Drivers in Aldosterone-Producing Adenomas and Nodules: Insights from a Brazilian Cohort of Primary Aldosteronism

Sunday, June 14, 2026

2:45 PM - 3:00 PM CT

Location: Room W187

Co-Author(s)

AG

Augusto Guimamares, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
TG

Tatiana Goldbaum, MD, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Sao Paulo, Brazil
FL

Felipe Ledesma, MD

Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, BR
Sao Paulo, Brazil
FF

Felipe Freitas-Castro, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
LS

Lucas Santana, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
JS

Jose Antonio Sobrinho, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
LR

Lucas B Rossetti, MD, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
JO

Jessica Okubo, MD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
EK

Eduardo Kawahara, MD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
LB

Luiz Bortolotto, MD, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
VS

Victor Srougi, n/a

Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, bR
São Paulo, Brazil
FT

Fabio Tanno, MD, PhD

Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
WN

William Nahas, MD, PhD

Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
JC

Jose Chambo, MD, PhD

Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
MP

Maria Adelaide Pereira, MD, PhD

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
LD

Luciano Drager, MD, PhD

Unidade de Hipertensão, Disciplina de Nefrologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
Sao Paulo, Brazil
MF

Maria B. V. Fragogo, MD PhD (she/her/hers)

Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BR
São Paulo, Sao Paulo, Brazil
Ana Claudia Latronico, MD, PhD (she/her/hers)

Full Professor
Sao Paulo Medical School, Sao Paulo University
Sao Paulo, BRAZIL
Berenice Bilharinho Mendonca, MD, PhD (she/her/hers)

Senior Professor
University Sao Paulo Fac Medical
Sao Paulo, Sao Paulo, Brazil
MZ

Maria Claudia Zerbini, MD, PhD

Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, BR
Sao Paulo, Brazil

Oral Abstract Presenter(s)

Madson Almeida, MD, PhD

Professor
University of Sao Paulo
Sao Paulo, BRAZIL

Senior Author/Primary Investigator(s)

Madson Almeida, MD, PhD

Professor
University of Sao Paulo
Sao Paulo, BRAZIL

Background: The Brazilian population represents a mosaic of genetic diversity resulting from admixture ancestries. Given reported disparities in primary aldosteronism (PA) genetics across ethnicities, we investigated the genetic spectrum of aldosterone-producing adenomas (APAs) and nodules (APNs) with classical histology in a Brazilian cohort.

Methods: We included 62 lesions (one case with bilateral APAs) from 61 consecutive patients (median age at PA diagnosis 49 years, 59% women) with PA and classical histology, defined by CYP11B2 immunostaining (HISTALDO consensus). Somatic DNA was extracted from CYP11B2-positive areas of the dominant lesions. Hotspot regions of KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 were initially analyzed by Sanger sequencing. Whole-exome sequencing (WES) of paired somatic and germline DNA was subsequently performed in cases without driver variants.

Results: Histopathology showed combined APA + aldosterone-producing micronodules (APMs) as the most frequent subtype (n=29, 47.54%), followed by isolated APA (n=20, 32.79%) and APN (n=5, 8.2%). Somatic pathogenic or likely variants were identified in 82.26% of lesions: KCNJ5 (n=35, 56.45%), ATP2B3 (n=7, 11.29%), CACNA1D (n=5, 8.06%) and ATP1A1 (n=4, 6.45%). Nine novel variants were identified, including three in ATP2B3 (two exon 8 in-frame deletions and one missense), three in KCNJ5, two in CACNA1D, and one in CTNNB1. The frequency of ATP2B3 variants (11.29%) was significantly higher than that reported in other cohorts (4.06%) from different ethnicities (p=0.0053). ATP2B3-mutated tumors occurred predominantly in older men and were smaller in size compared with wild-type tumors. In isolated APAs, KCNJ5 was the most frequent driver (60%), whereas ATP2B3 and ATP1A1 variants each accounted for 10% of cases. In contrast, APNs displayed a more heterogeneous molecular profile, with a higher representation of CACNA1D (40%), alongside KCNJ5 (20%) and ATP1A1 (20%). In cases with combined features, such as APA associated with APN, APMs, or APDH, the dominant lesion maintained its characteristic variant pattern, with KCNJ5 remaining the leading driver, particularly in APA + APM cases (62.07%). KCNJ5 enrichment was observed in classical APA (isolated or associated with APMs), whereas greater genetic heterogeneity was found in APN or mixed presentations (APA + APN and APA + APDH).

Conclusion: We confirmed the predominance of known somatic drivers and identified a uniquely high frequency of ATP2B3 variants, refining their clinical phenotype. Our findings indicate that within the spectrum of classical histology in PA, the molecular landscape is largely defined by the dominant aldosterone-producing lesion. These findings underscore the influence of population-specific genetic backgrounds and expand the global understanding of PA genetics.