ECE2022 Poster Presentations Adrenal and Cardiovascular Endocrinology (87 abstracts)
Prevalence and clinical features of ARMC5 mutations in a single centre cohort of patients with bilateral adrenal incidentalomas
Sofia Frigerio 1,2 , Valentina Morelli 3 , Francesca Marta Elli 1 , Walter Vena 4 , Maria Antonia Maffini 1 , Camilla Lucca 1 , Matteo Piu 1 , Nicola Mora 1 , Serena Palmieri 1 , Giovanna Mantovani 1,2 & Maura Arosio 1,2
1Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 2University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 3IRCCS Istituto Auxologico Italiano, Unit for Bone Metabolism Diseases and Diabetes & Lab of Endocrine and Metabolic Research, Milan, Italy; 4IRCCS Humanitas Research Hospital, Unit of Endocrinology, Diabetology and Medical Andrology, Rozzano, Italy
Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome (CS). Some familial forms have been associated to gene ARMC5 (Armadillo repeat-containing protein 5) inactivating mutations. This study aimed to evaluate the prevalence and the complications of ARMC5 mutations in our cohort of patients with bilateral adrenal incidentalomas (BAI).
Methods: 72 patients, referred to our Center for BAI, were analysed to identify pathogenetic single nucleotide variants (SNVs) and/or structural rearrangements (duplications/deletions, termed as copy number variants, CNVs) involving ARMC5 gene. We also evaluated the prevalence of glycometabolic complications, arterial hypertension (AH), nodules dimension and HPA axis parameters. Subclinical hypercortisolism (SH) was defined by cortisol levels after 1 mg overnight dexamethasone suppression (1 mgDST) ≥1.8 μg/dl.
Results: 48/72 patients presented SH. A germline mutation of ARMC5was found in 9 SH patients (12.5% of the whole population), 7 SNVs and 2 CNVs (Group1). The remaining 39 SH patients were found to be wild type (WT) (Group2). No germline mutations were found among patients without SH (Group3; n=24). Moreover, we also looked for the presence of somatic ARMC5 mutations in the tissue of 7 patients who had undergone adrenalectomy and we found that 100% presented CNVs (2 patients of Group1 and 5 patients of Group2). Age, gender and prevalence of obesity, AH, diabetes mellitus, dyslipidaemia and osteoporosis were comparable among the three groups. Patients of Group1 showed a larger diameter of the adenoma than patients of Group3 (5.77 ± 2.64 cm vs 3.40 ± 1.18 cm.; P=0.000), but comparable to Group2 (5.77 ± 2.64 cm vs 4.82 ± 1.62 cm, P=0.124). However, all the 4 patients who presented at least one nodule over 5 cm of diameter belonged to Group1. Basal ACTH levels were higher in Group3 compared to Group1 and Group2 (16.41 ± 7.50 ng/l, 10.61 ± 2.82 ng/l, 11.37 ± 6.50 ng/l respectively, P<0.05). Similarly, cortisol suppression after 1 mgDST was significantly lower in Group1 (7.06 ± 6.32 μg/dl) as compared to Group2 (3.97 ± 3.27 μg/dl) and Group3 (1.26 ± 0.35 μg/dl) (P<0.01).
Conclusion: Prevalence of germline ARMC5 mutations in our BAI cohort was 12.5%, reaching up to 18.8% in subjects with SH. Mutation carriers seem to have poorer cortisol suppression to low dose DST and larger nodule diameter but similar metabolic co-morbidities as compared to WT patients. Further studies are needed to elucidate the meaning of the somatic CNVs observed in patients without germline mutations.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more