Endocrine Abstracts

Introduction: Armadillo-containing repeat protein 5 gene (ARMC5) is a tumor suppressor gene expressed in different human tissues. Inactivating germline and somatic mutations of the gene are involved in the pathogenesis of primary bilateral macronodular adrenocortical hyperplasia (PBMAH). These mutations are mainly met in the familial form of PBMAH and are associated with a more severe Cushing Syndrome, meningiomas and T-cell immune response defects. However, the role of ARMC5 mutations in the pathogenesis of unilateral adrenal cortical adenomas is yet poorly investigated.

Case presentation: A 61 -year- old female was referred to our outpatient clinic due to a left adrenal incidentaloma and an 18F-FDG PET/CT with pituitary and left adrenal uptake. For the last year, she presented progressively worsening fatigue, weakness, headaches, depression and deregulation of arterial blood pressure under her regular treatment. Further diagnostic work up with adrenal CT revealed an inhomogeneous left adrenal lesion, 5,3 X 4,5 cm, with low wash out (absolute 27,8%, relative 20,4%) and pituitary MRI showed pituitary and intracranial lesions suggestive of meningiomas. Hormonal assessment revealed complete pituitary hormone sufficiency and ACTH independent cortisol hypersecretion. Initially the patient underwent a left adrenalectomy with subsequent remission of hypercortisolism, and afterwards on resection of the pituitary tumor. Pathology report was compatible with adrenal adenoma and meningioma, respectively. Genetic screening revealed a rare germline ARMC5 mutation [c.2192C>G (p.Pro731Arg, P731R), heterozygosity]. Post-surgically, the patient is under hormone replacement therapy with hydrocortisone and levothyroxine, and is regularly followed up at our outpatient clinic. Family screening is pending.

Discussion: This a rare case of a patient with ARMC5 mutation presenting with Cushing Syndrome, due to unilateral adrenal adenoma, and pituitary and intracranial meningiomas. Though the relationship between ARMC5 mutations and PBMAH has been established, ARMC5 mutations are considered very rare in unilateral adrenal adenomas. On the other hand, patients with meningiomas presented higher prevalence of adrenal nodules in a recent study. Further research is needed to elucidate the association between meningiomas, adrenal adenomas and ARMC5 mutations.