ECE2018 Poster Presentations: Adrenal and Neuroendocrine Tumours Adrenal cortex (to include Cushing's) (70 abstracts)
A new ARMC5 mutation responsible for primary bilateral macronodular adrenal hyperplasia
Isabel Mazarico 1 , David Subías 1 , Miriam Guitart 2 , Rosa Maria Bella 3 , Lara Albert 1 , Florencia Luchtenberg 1 , Irene Berges 1 , Ismael Capel 1 , Albert Cano 1 , Laia Casamitjana 1 , Olga Giménez-Palop 1 , Assumpta Caixàs 1 & Mercedes Rigla 1
1Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari. Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain; 2Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain; 3Pathology Service, Parc Taulí Hospital Universitari. Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause (<2 percent) of endogenous Cushing’s syndrome, usually characterized by enlarged adrenal glands containing multiple functioning nonpigmented macronodules. PBMAH was thought to be sporadic, but recently a genetic component has been described. Specifically, inactivating mutations in ARMC5 (Armadillo-repeat containing 5), a suppressor gene, have been found in many familial cases of PBMAH, and are thought to be the most common genetic cause of this disorder. We report a case of PBMAH with a not previously reported ARMC5 mutation.
Case report: A 65-year-old man was referred for the study of hypogonadotropic hypogonadism. Blood test revealed an elevated 0800 h cortisol of 27.5 μg/dl. 24-hour urinary free cortisol (UFC) level was high (201.7 μg/24 h) and after 1mg dexamethasone overnight his baseline cortisol failed to suppress (21.5 μg/dl). Baseline ACTH was undetectable (<1 pg/ml). The computed tomography (CT) scan revealed multiple large nodules throughout both adrenal glands consistent with benign cortical adenomas (right gland 63×31 mm and left gland 41×39 mm). Functional study was completed without showing other disorders. Screening for aberrant adrenal receptors showed a total response to terlipressin (+163.98%) and a partial response to upright posture (+39.57%). A molecular analysis by sequencing ARMC5 gene identified a heterozygous splicing mutation, c.476-2A>T (NM_0011005247.1), not previously reported. The mutation will most likely lead to an in-frame loss of exon 2 from the transcript. Therefore, we confirmed the diagnosis of PBMAH type 2 caused by a mutation in the ARMC5 gene. Genetic testing of the patient’s son did not show the mutation. Adrenalectomy of the largest gland was performed, achieving normal UFC levels and restitution of the gonadal function.
Conclusion: PBMAH is an underrecognized genetic condition that can lead to Cushing’s syndrome with the consequent increase of the morbimortality. Identifying a pathogenic mutation of ARMC5 and performing a genetic screening for predisposition to PBMAH could lead to earlier diagnosis and prevention of long-term complications of Cushing’s syndrome.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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