Endocrine Abstracts

Germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with primary bilateral macronodular adrenal hyperplasia (PBMAH). PBMAH is a rare etiology of Cushing’s syndrome. This gene has been proposed to acts as a tumor-suppressor gene. A 36-years old female presented to us with clinical signs of hypercortisolism. ACTH dependent Cushing’s syndrome was confirmed soon after. Pituitary magnetic resonance imaging (MRI) revealed hypointensed lesion, 12mm in size, in right part of the pituitary gland. At the same time abdominal MRI described bilateral adrenal hyperplasia. Transsphenoidal pituitary surgery was performed and ACTH secreting pituitary adenoma with Crooke’s hyaline was found on patohystology. Genetic screening for MEN1 and AIP were negative, but germline mutation was identified in exon 2 (I170V) of ARMC5 gene. LOH in tumor tissue is in course. We continuated 3 months follow up and patient was disease free. Six moths after surgery patient had positive hormonal and MRI findings for pituitary adenoma remnant. Abdominal MRI was still unchainged. In further course patient was treated with stereotactic radiosurgery. On her regular follow up pituitary MRI still shows tumor remnant (6 mm) and adrenal hyperplasia is same in diameter. Functional testing demonstrate lack of cortisol supresion in overnight dexamethasone suppression test and high normal levels of ACTH. We presented a patient with Cushing’s disease, bilateral adrenal hyperplasia and ARMC5 mutation. After the treatment, our patient still has endogenous hypercortisolism and inadequate ACTH secretion which is probably due to Cushing’s disease. It is also possible that adrenal hyperplasia contribute to hypercortisolemia due to ARMC5 mutation. So far we know that ARMC5 mutation lead to PBMAH. Recent studies have shown that the various ARMC5 isoforms were present in most endocrine tissues including the pituitary, adrenal glands and the pancreas. Future studies are necessary and could possibly indicate if ARMC5 mutation is responsible for multi-glandular tumor syndrome.