Evidence map›Paper›PMID 39774659›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

PDE11A Is a Phenotype Modulator of Primary Bilateral Macronodular Adrenal Hyperplasia: Results of a 334-Patient Series.

Patricia Vaduva, Lucas Bouys, Anne Jouinot, Stephanie Espiard, Albain Chansavang, Annabel Berthon, Mario Néou, Anna Vaczlavik, Florian Violon, Helaine Charchar and 13 more

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In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Patricia VaduvaInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.ORCID 0000-0003-3195-1629
Lucas BouysInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.ORCID 0000-0003-1743-1598
Anne JouinotInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.
Stephanie EspiardDepartment of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille 59000, France.
Albain ChansavangDepartment of Genomic Medicine of Tumors and Cancers, Cochin Hospital, APHP, Paris 75014, France.
Annabel BerthonInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.ORCID 0000-0002-5576-9525
Mario NéouInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.
Anna VaczlavikDepartment of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris 75014, France.
Florian ViolonInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.ORCID 0000-0002-7990-3434
Helaine CharcharDepartment of Endocrinology, Adrenal Unit, University of Sao Paulo, São Paulo 03178-200, Brazil.
Matthias KroissDepartment of Internal Medicine IV, LMU University Hospital and Ludwig-Maximilians-Universität München, Munich 80539, Germany.
Gerald RaverotFederation of Endocrinology, Hospices Civils de Lyon, Bron 69029, France.ORCID 0000-0002-9517-338X
Helene LasolleFederation of Endocrinology, Hospices Civils de Lyon, Bron 69029, France.ORCID 0000-0002-5027-7660
Laurence GuignatDepartment of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris 75014, France.
Rossella LibéDepartment of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris 75014, France.
Guillaume AssiéInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.
Antoine TabarinDepartment of Endocrinology, Diabetology, Metabolic Diseases and Nutrition, University Hospital Centre of Bordeaux, Bordeaux 33000, France.ORCID 0000-0003-1231-3306
Peter KamenickyDepartment of Endocrinology and Rare Reproductive Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre 94270, France.ORCID 0000-0002-1994-4226
Eric PasmantDepartment of Genomic Medicine of Tumors and Cancers, Cochin Hospital, APHP, Paris 75014, France.ORCID 0000-0002-1881-8762
Maria FragosoDepartment of Endocrinology, Adrenal Unit, University of Sao Paulo, São Paulo 03178-200, Brazil.
Constantine StratakisEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Bruno RagazzonDepartment of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris 75014, France.
Jérôme BertheratInstitut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes University, Paris 75014, France.ORCID 0000-0003-2551-3008

Funding

Fondation pour la Recherche Médicale EQU201903007854French Society of EndocrinologyIPSEN
6 · The paper itself

Abstract

contextPrimary bilateral macronodular adrenal hyperplasia (PBMAH), the most common cause of Cushing syndrome due to bilateral nodules, is a heterogeneous disease at the clinical, hormonal, and morphological levels. ARMC5-inactivating pathogenic variants are causative of PBMAH, and rare variants of PDE11A have been associated with PBMAH.

objectiveThe aim of this study, on a large cohort of individuals with PBMAH from Europe and America, was to study the ARMC5 and PDE11A genotype to determine the genotype/phenotype correlation and to investigate the hypothesis that PDE11A could be a modifying gene of the adrenal phenotype.

methodsLeukocyte DNA of 354 PBMAH index cases was sequenced for ARMC5 and PDE11A genes by next-generation sequencing. Phenotypic characteristics of 334 of these patients were analyzed to study the genotype/phenotype correlations.

resultsSeven out of 16 PDE11A variants were considered damaging according to in silico predictions: 6 missense variants (p.Tyr727Cys, p.Met623Arg, p.Tyr658Cys, p.Ag867Trp, p.Asn298Ser, p.Glu840Lys) and 1 stop-gain variant (p.Arg307Ter). In the cohort, 11.4% of patients had one of these variants and 19.2% had ARMC5-pathogenic variants. There was no statistically significant difference in the distribution of PDE11A-damaging variants according to ARMC5 status (P = .83; OR = 0.79; 95% CI, 0.26-2.03) nor in the distribution of ARMC5 pathogenic variants according to PDE11A status (P = .83; OR = 0.81; 95% CI, 0.27-2.04). Patients with PDE11A-damaging variants had lower urinary free cortisol (0.7 vs 1.25 upper limit of normal; P = .0002), midnight plasma cortisol (157.81 vs 222.19 nmol/L, P = .016), and number of adrenal nodules (3.46 vs 4.74; P = .048) compared to PDE11A wild-type patients. Patients with ARMC5-pathogenic variants had a more severe phenotype with more frequent comorbidities and were more often treated by adrenalectomy (60%).

conclusionPDE11A appears to be a modulator of PBMAH phenotype, damaging variants being associated with an attenuated form. This may contribute to the heterogeneity of PBMAH and could affect patient management.

Indexed as

Phosphoric Diester Hydrolases3',5'-Cyclic-GMP PhosphodiesterasesAdolescentAdrenal Hyperplasia, CongenitalAdultAgedArmadillo Domain ProteinsCohort StudiesCushing SyndromeFemaleGenetic Association StudiesGenotypeHumansMaleMiddle AgedMutation, Missense3',5'-Cyclic-GMP PhosphodiesterasesArmadillo Domain ProteinsARMC5 protein, humanPDE11A protein, humanPhosphoric Diester HydrolasesARMC5Cushing syndromePDE11Aphenotypeprimary bilateral macronodular adrenal hyperplasia (PBMAH)

Identifiers

PMID39774659
PMCPMC12641522

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