Evidence map›Paper›PMID 38888173›Full record

ArticleThe Journal of clinical endocrinology and metabolism2024

Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.

Brasilina Caroccia, Livia Lenzini, Giulio Ceolotto, Francesca Gioco, Andrea Benetti, Alessandra Giannella, Hala Ajjour, Francesca Galuppini, Gianmaria Pennelli, Teresa Maria Seccia and 2 more

Erratum issuedAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. A novel compound heterozygous mutation inFrontiers in medicine · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Brasilina CarocciaSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.
Livia LenziniSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.ORCID 0000-0001-6146-3015
Giulio CeolottoSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.ORCID 0000-0002-4687-8033
Francesca GiocoSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.
Andrea BenettiDivision of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua, Padua 35122, Italy.
Alessandra GiannellaDivision of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua, Padua 35122, Italy.
Hala AjjourSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.
Francesca GaluppiniDepartment of Medicine, Surgical Pathology Unit, University of Padua, Padua 35122, Italy.
Gianmaria PennelliDepartment of Medicine, Surgical Pathology Unit, University of Padua, Padua 35122, Italy.
Teresa Maria SecciaSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.ORCID 0000-0002-3639-4086
Celso Gomez-SanchezG.V. (Sonny) Montgomery VA Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Gian Paolo RossiSpecialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.ORCID 0000-0002-7963-0931

Funding

Department of MedicineDIMAR ExcellenceFoundation for advanced ResearchIn Hypertension and CArdiovascular
6 · The paper itself

Abstract

contextThe search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas.

objectiveTo investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS).

methodsWe investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS.

resultsDouble IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (χ2 = 22.492, P < .001).

conclusionNGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of patients with aldosterone-producing adenomas.

Indexed as

Cytochrome P-450 CYP11B2G Protein-Coupled Inwardly-Rectifying Potassium ChannelsHyperaldosteronismImmunohistochemistryMutationSteroid 11-beta-HydroxylaseAdrenal Cortex NeoplasmsAdrenocortical AdenomaAdultAgedFemaleHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedCytochrome P-450 CYP11B2G Protein-Coupled Inwardly-Rectifying Potassium ChannelsKCNJ5 protein, humanSteroid 11-beta-HydroxylaseCYP11B2 immunohistochemistrykir3.4 channelnext-generation sequencingprimary aldosteronismSanger sequencing

Identifiers

PMID38888173
PMCPMC11918620

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.