High prevalence of CYP11B2-positive aldosterone-producing micronodules in subjects without known adrenal diseases

Juhani Isojarvi; Antero Ylanen; Antti Virtanen; Helena Leijon; Tiina Vesterinen; Heini Huhtala; Ilkka Porsti; Marianna Viukari; Eeva Kokko; Niina Matikainen; Pasi I Nevalainen

doi:10.1530/endoabs.110.P54

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Endocrine Abstracts (2025) 110 P54 | DOI: 10.1530/endoabs.110.P54

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

High prevalence of CYP11B2-positive aldosterone-producing micronodules in subjects without known adrenal diseases

Juhani Isojärvi ¹ , Antero Ylänen ^1,2 , Antti Virtanen ³ , Helena Leijon ⁴ , Tiina Vesterinen ⁴ , Heini Huhtala ⁵ , Ilkka Pörsti ^1,2 , Marianna Viukari ⁶ , Eeva Kokko ¹ , Niina Matikainen ⁶ & Pasi I Nevalainen ^1,2

Author affiliations

¹Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland; ²Tampere University Hospital, Department of Internal Medicine, Tampere, Finland; ³Finnish Institute for Health and Welfare, Forensic Medicine Unit, Helsinki, Finland; ⁴Helsinki University Hospital and University of Helsinki, HUS Diagnostic Center, HUSLAB, Department of Pathology, Helsinki, Finland; ⁵Tampere University, Health Sciences, Faculty of Social Sciences, Tampere, Finland; ⁶Helsinki University Hospital, ENDO-ERN (European Reference Network on Rare Endocrine Conditions) and University of Helsinki, Endocrinology, Helsinki, Finland

JOINT1349

Background: The zona glomerulosa (ZG) of the adrenal cortex synthesizes aldosterone, a key hormone involved in blood pressure regulation. Previous studies have shown an inverse correlation between age and both the continuity of aldosterone synthase (CYP11B2) expression and the area expressing CYP11B2. However, the significance of CYP11B2 discontinuity in the development of primary aldosteronism remains unclear. This study aimed to investigate patient demographics and explore the localization, symmetry, and clinical relevance of adrenal cortical lesions expressing CYP11B2.

Methods: This cross-sectional study included 145 consecutive autopsied cases from southern Finland without known adrenal diseases, all of whom had died from exogenic causes (trauma, suicide, or intoxication). Immunohistochemical CYP11B2 staining was performed on both adrenal glands and analyzed following the HISTALDO consensus guidelines. A four-grade classification system was used to assess CYP11B2 continuity: 1) diffuse CYP11B2 positivity (normal), 2) twenty or more aldosterone-producing micronodules (APMs ≥20), 3) APMs <20, and 4) aldosterone-producing nodules (APNs). Autopsy findings were recorded, and clinical data including diagnoses of hypertension and antihypertensive medication prescriptions from the past 10 years were obtained from national registries. This sub-study was registered at ClinicalTrials.gov (NCT05446779).

Results: The study cohort included 104 males (71.7%) and 41 females (28.3%), with a mean age of 53.7 years (range: 26.1–76.4 years). Among the participants, 12 (8.3%) exhibited bilateral diffuse CYP11B2 positivity, while APMs were identified in 131 subjects (90.3%). Of these, 42 cases (29.0%) had APMs ≥20 and 89 cases (61.4%) had APMs <20. Two cases (1.4%) with APNs were detected. Both APMs ≥20 and APMs <20 showed notable symmetry between the two adrenals, with concordant CYP11B2 continuity in 76.2% and 68.5% cases, respectively. CYP11B2 continuity did not associate with age, diagnosis of hypertension, or use of antihypertensives. Heart weight was significantly higher in subjects with APMs <20 compared to those with APMs ≥20 or diffuse CYP11B2 positivity (P=0.048 and P=0.021, respectively).

Conclusions: Bilateral diffuse CYP11B2 positivity, considered as normal ZG structure, was surprisingly rare. APMs were frequently observed in the adrenal glands, showing notable side-to-side symmetry. Heart weight was significantly associated with decreased CYP11B2 continuity. However, neither the diagnosis of hypertension nor the use of antihypertensive medications was related with the CYP11B2 continuity categories. Contrary to previous studies, age did not associate with CYP11B2 discontinuity. Our cross-sectional results indicate that bilateral CYP11B2 discontinuity is a frequent finding.