Skip to main content
ENDO 2026 Main banner

Cardiovascular Endocrinology

ORF31-02 - Aldosterone-Producing Adenomas Harboring ATP1A1 and ATP2B3 Mutations: An International Multicenter Study

Sunday, June 14, 2026
1:50 PM - 1:55 PM CT
Location: Room W187
Disclosure(s):
Anand Vaidya, MD, MMSc: No relevant disclosure to display



Background: Somatic aldosterone-driver mutations can be identified in >90% of patients with primary aldosteronism (PA) who undergo adrenalectomy, and these mutations cluster differently across sexes and races. Overall, mutations in KCNJ5 (which encodes the potassium channel Kir3.4) and CACNA1D (which encodes the voltage-dependent L-type Ca2+ channel subunit 1D) are most common. In contrast, mutations in ATP1A1 and ATP2B3, which encode the Na+/K+ ATPase α-1 subunit and the Ca2+ ATPase 3 respectively, are relatively rare and have been grouped as ATPase mutations in prior studies. Little is known about potential differences in the clinical and biochemical phenotypes of these two genotypes.

Methods: This international collaboration of 10 centers from 5 continents included patients with PA found to harbor pathogenic variants in ATP1A1 or ATP2B3. Clinical data were collected from medical records. Liquid chromatography-tandem mass spectrometry was used to quantify 17 steroids in available peripheral and adrenal vein blood, both before and after cosyntropin stimulation.

Results: A total of 189 participants with ATPase-mutated aldosterone-producing adenomas were identified (135 ATP1A1 and 54 ATP2B3). Mean age was 59 ± 11 years, and 160 (84.7%) were men. Age and sex distribution was similar in the two groups. The ATP1A1 group had more White individuals (55% vs. 33%), while Asians were more prevalent in the ATP2B3 group (20% vs. 11%, p=0.02). Patients with ATP2B3 mutations had lower serum potassium levels (3.2 [2.8-3.6] vs. 3.6 [3.2-4.1] mmol/L, p< 0.01), higher lateralization indices, and more profound contralateral suppression, particularly after cosyntropin stimulation (32.18 [15.99-58.24] vs. 15.09 [6.86-33.57]; and 0.09 [0.06-0.21] vs. 0.20 [0.09-0.43], respectively, p< 0.01 for both). Postoperative biochemical cure was achieved in 98% of those with ATP2B3 mutations vs. 81% in those with ATP1A1 mutations (p = 0.01). Serum for peripheral steroid profiling was available in 59 patients (46 with ATP1A1 and 13 patients with ATP2B3). The ATP2B3 group showed higher concentrations of aldosterone (34 [20-76] ng/dL vs. 18 [9-34] ng/dL, p=0.04) and 17-hydroxyprogesterone (101 [50-249] ng/dL vs. 48 [34-75] ng/dL, p=0.02), and a trend for higher 11-deoxycorticosterone and 18-hydroxycortisol.

Conclusion: ATPase mutations are most common among middle-aged men with lateralized PA. Compared with ATP1A1, ATP2B3 mutations are associated with higher hormonal activity, more profound lateralization, and higher likelihood of post-operative biochemical cure.