Skip to content
DraconiticResearch
Search Sources API
201,683 studies31 sourcesUpdated 19 min ago
Peer-reviewedCC BY 4.0Histopathology

Histopathological stratification of primary aldosteronism using the CYP11B2 size ratio: first evaluation in clinical routine

  • Adam Stenman1,2
  • Tim Nilsson1
  • Henrik Falhammar2,3
  • C. Christofer Juhlin4,5
5 affiliations
  1. 1Department of Breast, Endocrine Tumors and Sarcoma Karolinska University Hospital Stockholm Sweden
  2. 2Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
  3. 3Department of Endocrinology Karolinska University Hospital Stockholm Sweden
  4. 4Department of Oncology‐Pathology Karolinska Institutet Stockholm Sweden
  5. 5Department of Pathology and Cancer Diagnostics Karolinska University Hospital Stockholm Sweden
Read full textDOICite

Abstract

Background: In primary aldosteronism (PA), the HISTALDO framework classifies aldosterone‐producing lesions as ‘classical’ (solitary nodule) or ‘non‐classical’ (multinodular or diffuse) based on CYP11B2 immunohistochemistry, but interpretation is complicated by frequent micronodules, even in patients without PA. The CYP11B2 size ratio (B2R), a quantitative measure of size disproportion between CYP11B2‐positive nodules, offers an objective way to assess lesion architecture and has shown value in predicting cure versus relapse. In this study, diagnostic classification was intentionally B2R‐guided, generating a modified HISTALDO B2R system in clinical routine.

Objective: Prospective evaluation of the prognostic value of B2R‐guided classification in routine pathology and assessment of postoperative outcomes across B2R‐defined subgroups.

Methods: Specimens of 70 adrenalectomies underwent multisection CYP11B2 staining; 61 patients had at least 6 months of follow‐up (mean age 53 years, 54% were females). All had adrenal vein sampling and confirmatory testing before unilateral laparoscopic adrenalectomy. Imaging showed unilateral findings in 51%, bilateral in 8% and no detectable nodules in 41%. A B2R ≥8.1 defined classical lesions; B2R < 8.1 non‐classical. Outcomes at 6–12 months were assessed using PASO criteria, which classify biochemical and clinical success as absent, partial or complete.

Results: Biochemical cure was achieved in 95% of patients with classical B2R morphology, compared with 40% of those with non‐classical B2R morphology (p < 0.001). Complete clinical success was also significantly more frequent in the classical B2R group than in the non‐classical group (57% versus 25%, p = 0.0235). Medication‐based measures supported these findings: patients with classic histology showed a trend towards reductions in antihypertensive medication expressed as defined daily doses (DDD) (median ΔDDD 2.83 versus 2.00, p = 0.1254), and a significantly greater reduction in potassium supplementation (median ΔDDD 1.25 versus 0.00, p < 0.001) compared to those with non‐classical histology.

Conclusions: B2R‐guided HISTALDO yields biologically distinct subgroups with clear prognostic separation. Earlier work using the original HISTALDO definition reported ~40%–45% persistent biochemical aldosteronism in non‐classical cases. Our findings reproduce this poor non‐classical outcome profile in a larger and more consistently defined B2R‐classified cohort. Importantly, incorporating B2R reduces misclassification of tumours as non‐classical when background nodularity is present despite a dominant CYP11B2‐positive lesion.

Related

  1. Primary Aldosteronism: Evaluation and Management in the Hypertensive Patient
    Maria Balhara, Lily Owei, John Demko +2
    Current Hypertension ReportsPeer-reviewedCC BY 4.0Full textEndocrinology & metabolismPMC
  2. The Aldosterone–Immune Axis in Primary Aldosteronism: Linking Adrenal Pathogenesis to Systemic Inflammation and Target-Organ Damage
    Noorzaileen Eileena Zaidi, Elena Aisha Azizan, Adli Ali
    BiomedicinesPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. New genetic insights into primary aldosteronism—maybe
    Lawrence S Kirschner
    Journal of the Endocrine SocietyPeer-reviewedPublic domainFull textEndocrinology & metabolismPMC
  4. AI-Based Screening Approach for Primary Aldosteronism Using Longitudinal Electronic Health Records
    F. G. Lee, A. Choudhary, L. Y. Li-Han +8
    medRxivPreprintAll rights reservedFull textEndocrinology & metabolismmedRxiv
  5. Leveraging deep learning for prognostic stratification of hepatocellular carcinoma using histopathological images
    Dengbin Wu, Jiaoyue Zhang, Mian Shi +4
    Frontiers in oncologyPeer-reviewedCC BYFull textOncologyEurope PMC

Cite

BibTeXRIS
BibTeX
@article{stenman2026histopathological,
  title = {{Histopathological stratification of primary aldosteronism using the CYP11B2 size ratio: first evaluation in clinical routine}},
  author = {Adam Stenman and Tim Nilsson and Henrik Falhammar and C. Christofer Juhlin},
  journal = {Histopathology},
  year = {2026},
  month = aug,
  doi = {10.1111/his.70254},
  url = {https://doi.org/10.1111/his.70254},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Histopathological stratification of primary aldosteronism using the CYP11B2 size ratio: first evaluation in clinical routine
AU  - Adam Stenman
AU  - Tim Nilsson
AU  - Henrik Falhammar
AU  - C. Christofer Juhlin
PY  - 2026
DA  - 2026/08/04
JO  - Histopathology
DO  - 10.1111/his.70254
UR  - https://doi.org/10.1111/his.70254
AB  - Background: In primary aldosteronism (PA), the HISTALDO framework classifies aldosterone‐producing lesions as ‘classical’ (solitary nodule) or ‘non‐classical’ (multinodular or diffuse) based on CYP11B2 immunohistochemistry, but interpretation is complicated by frequent micronodules, even in patients without PA. The CYP11B2 size ratio (B2R), a quantitative measure of size disproportion between CYP11B2‐positive nodules, offers an objective way to assess lesion architecture and has shown value in predicting cure versus relapse. In this study, diagnostic classification was intentionally B2R‐guided, generating a modified HISTALDO B2R system in clinical routine.  Objective: Prospective evaluation of the prognostic value of B2R‐guided classification in routine pathology and assessment of postoperative outcomes across B2R‐defined subgroups.  Methods: Specimens of 70 adrenalectomies underwent multisection CYP11B2 staining; 61 patients had at least 6 months of follow‐up (mean age 53 years, 54% were females). All had adrenal vein sampling and confirmatory testing before unilateral laparoscopic adrenalectomy. Imaging showed unilateral findings in 51%, bilateral in 8% and no detectable nodules in 41%. A B2R ≥8.1 defined classical lesions; B2R < 8.1 non‐classical. Outcomes at 6–12 months were assessed using PASO criteria, which classify biochemical and clinical success as absent, partial or complete.  Results: Biochemical cure was achieved in 95% of patients with classical B2R morphology, compared with 40% of those with non‐classical B2R morphology (p < 0.001). Complete clinical success was also significantly more frequent in the classical B2R group than in the non‐classical group (57% versus 25%, p = 0.0235). Medication‐based measures supported these findings: patients with classic histology showed a trend towards reductions in antihypertensive medication expressed as defined daily doses (DDD) (median ΔDDD 2.83 versus 2.00, p = 0.1254), and a significantly greater reduction in potassium supplementation (median ΔDDD 1.25 versus 0.00, p < 0.001) compared to those with non‐classical histology.  Conclusions: B2R‐guided HISTALDO yields biologically distinct subgroups with clear prognostic separation. Earlier work using the original HISTALDO definition reported ~40%–45% persistent biochemical aldosteronism in non‐classical cases. Our findings reproduce this poor non‐classical outcome profile in a larger and more consistently defined B2R‐classified cohort. Importantly, incorporating B2R reduces misclassification of tumours as non‐classical when background nodularity is present despite a dominant CYP11B2‐positive lesion.
SN  - 0309-0167
SN  - 1365-2559
ER  -