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Update on primary bilateral macronodular adrenal hyperplasia (PBMAH)

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Abstract

Primary bilateral macronodular adrenal hyperplasia (PBMAH), characterized by bilateral benign adrenal macronodules (>1 cm) potentially responsible for variable levels of cortisol excess, is a rare and heterogeneous disease. However, its frequency increases due to incidentally diagnosed cases on abdominal imaging carried out for reasons other than suspected adrenal disease. Mostly isolated, it can also be associated with dominantly inherited genetic conditions in rare cases. Considering the bilateral nature of adrenal involvement and the description of familial cases, the search of a genetic predisposition has led to the identification of germline heterozygous inactivating mutations of the putative tumor suppressor gene ARMC5, causing around 25% of the apparent sporadic cases. Rigorous biochemical and imaging assessment are key elements in the management of this challenging disease in terms of diagnosis. Treatment is reserved for symptomatic patients with overt or subclinical Cushing syndrome, and was historically based on bilateral adrenalectomy, which nowadays tends to be replaced by unilateral adrenalectomy or lifelong treatment with cortisol synthesis inhibitors.

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L.B. is recipient of research fellowships from the Cancer Research for Personalized Medicine (CARPEM) and from the Fondation ARC pour la Recherche contre le Cancer. W.A has received funding from the Wellcome Trust (Investigator Award WT209492/Z/17/Z) the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant BRC-1215-20009). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care UK. This research has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 633983 (ENSAT-HT). M.R. receives funding by the Else Kröner-Fresenius Stiftung (2012_A103 and 2015_A228) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Projektnummer: 314061271-TRR 205). JB laboratory is supported by the Agence Nationale pour la Recherche grant ANR-18-CE14-0008-01 and the Foundation pour la Recherche Médicale (EQU201903007854).

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Authors and Affiliations

  1. Institut Cochin, Université de Paris, Inserm U1016, CNRS UMR8104, 24 rue du Faubourg Saint-Jacques, 75014, Paris, France

    Lucas Bouys & Jérôme Bertherat

  2. Istituto Auxologico Italiano, IRCCS, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, ENDO-ERN HCP, University of Milan, Milan, Italy

    Iacopo Chiodini

  3. Institute of Metabolism and Systems Research, ENDO-ERN HCP, University of Birmingham, Birmingham, B15 2TT, UK

    Wiebke Arlt

  4. Medizinische Klinik und Poliklinik IV, ENDO-ERN HCP, Klinikum der Universität, Ludwig-Maximilians-Universität München, Ziemssenstraße 1, 80336, Munich, Germany

    Martin Reincke

  5. Centre de Référence Maladies Rares de la Surrénale, Service d’Endocrinologie, ENDO-ERN HCP, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France

    Jérôme Bertherat

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  1. Lucas Bouys
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  2. Iacopo Chiodini
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  3. Wiebke Arlt
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  4. Martin Reincke
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  5. Jérôme Bertherat
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Correspondence to Jérôme Bertherat.

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Conflict of interest

M.R. has received speakers and consultancy fees from Recordati and Novartis. J.B. has received speakers and consultancy fees from HRA pharma, Novartis, Corcept, and Recordati. I.C. has received speaker and consultancy fees from HRA pharma and Corcept. The other authors have no conflict of interest concerning this review article.

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Bouys, L., Chiodini, I., Arlt, W. et al. Update on primary bilateral macronodular adrenal hyperplasia (PBMAH). Endocrine 71, 595–603 (2021). https://doi.org/10.1007/s12020-021-02645-w

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