SUN-231 Clinical Implications of KCNJ5 Pathogenic Variants in Patients with Unilateral Primary Aldosteronism and Classical Histology
Bibliographic record
Abstract
Abstract Disclosure: A.G. Guimarães: None. T.S. Goldbaum: None. F. Ledesma: None. J. Okubo: None. E. Zanatta: None. L. Bortolotto: None. J. Chambo: None. M.C. Fragoso: None. M.A. Pereira: None. A. Pio-Abreu: None. G. Silva: None. J.V. Silveira: None. F. Consolim-Colombo: None. L. Drager: None. W. Nahas: None. A.C. Latronico: None. B.B. Mendonca: None. M. Zerbini: None. M.Q. Almeida: None. Background: KCNJ5 somatic pathogenic variants (PVs) have been associated with complete clinical success in cohorts of unilateral primary aldosteronism (PA). The histopathological evaluation of unilateral PA using aldosterone synthase (CYP11B2) immunostaining (HISTALDO) has enhanced the characterization of adrenal aldosterone-producing lesions. KCNJ5 is the most frequently mutated gene in classical histology, whereas CACNA1D somatic PVs are more common in non-classical histology. Our aim was to investigate the clinical benefit of somatic KCNJ5 PVs in patients with unilateral PA and classical histology. Methods: We conducted a cohort study involving 68 patients with unilateral PA and classical histology as defined by the HISTALDO classification. Classical histology was characterized by the presence of either a solitary aldosterone-producing adenoma (APA) or an aldosterone-producing nodule (APN). Genetic analysis of somatic PVs was performed on formalin-fixed paraffin-embedded samples guided by CYP11B2 staining. Biochemical and clinical outcomes were evaluated according to the PASO criteria. Results: Among the 68 patients with unilateral PA and classical histology, 25 (36.76%) were male and 43 (63.23%) were female, with a median age at diagnosis of 47 years (range: 20-74 years). APAs were diagnosed in 60 out of 68 cases (88.2%), while APNs were identified in 8 out of 68 cases (11.8%). Somatic PVs in the KCNJ5 gene were identified in 27 of the 68 cases (39.7%). Somatic KCNJ5 PVs were significantly more frequent in females than in males (14.8% vs. 85.2%, p= 0.003). The identified KCNJ5 PVs included p.G151R (n= 13), p.L168R (n= 10), p.Y158A (n= 2), p.G151G (n= 1) and p.E145Q (n= 1). The other mutated genes were ATP1A1 4.5% (n= 3), CACNA1D 1.5% (n= 1), and CTNNB1 1.5% (n= 1). The rate of complete hypertension remission was similar in patients with PA and classical histology, occurring in 38.5% of cases with somatic KCNJ5 PVs and 33.3% of cases without them. The presence of somatic KCNJ5 PVs showed no significant association with hypokalemia, resistant hypertension, aldosterone levels at diagnosis, or cortisol secretion. Conclusion: Our findings suggest that the higher rate of hypertension remission in patients with PA and classical histology is more likely attributed to histopathological features rather than the KCNJ5 gene itself. Support: São Paulo Research Foundation (FAPESP) grant number 2019/15873-6 (to MQA) and fellowship grant 2021/10363-0 (to AGG). Presentation: Sunday, July 13, 2025
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".