Background: Functional studies demonstrate that Armadillo repeat-containing 5 (ARMC5) gene, controls apoptosis and steroid synthesis. A germline mutations in ARMC5 are recently been associated with Cushing syndrome and possibly can be responsible for a broader tumor predisposition.
Case presentation: A 51-year-old woman presented with intermittent rectal bleeding. A colonoscopy revealed multiple colonic polyps, histopathological analysis showed tubular adenoma with low-grade dysplasia. A surgical treatment was advised. During the preoperative assessment, an enlargement of right adrenal gland was discovered on abdominal ultrasound and she was referred to endocrinologist. Patients past medical history was significant for hypertension. Her mother had endometrial cancer; 7 years after she died from liver cancer. Physical examination revealed typical Cushingoid features: a fool moon face and central obesity, without hirsutism. In laboratory studies, serum potassium was 2.8 mmol/l, sodium 142 mmol/l. A normal diurnal rhythm of cortisol was omitted: 0800 h 712 nmol/l, 0400 h 749 nmol/ and 0000 h 651 nmol/l, plasma adrenocorticotropic hormone (ACTH) supressed (0.6 ng/l). Serum cortisol level remained elevated after 1 mg overnight dexamethasone test (717 nmol/l). Levels of follicle-stimulating hormone, luteinizing hormone, thyrotropin, free thyroxine, parathyroid hormone, prolactin, testosterone, dehydroepiandrosterone, insulin-like growth factor 1, aldosteron/renin activity and 24-hour urinary catecholamines were within reference range. Further evaluation showed diabetes mellitus (plasma glucose at 120 min of oral glucose tolerance test 13.6 mmol/l, insulin 112.3 μIU/ml) and osteoporosis. Computed tomography confirmed an enlarged right adrenal gland, 31×36 mm. Pituitary magnetic resonance imaging showed a 6.5 mm-sized adenoma. The patient underwent laparoscopic right adrenalectomy and histopathological examination demonstrated a cortical adenoma. After surgery, Hydrocortisone supplementation was started. Genetic testing revealed germline mutation in ARMC5 (I170V; p.Ile170Val). At 2 months follow-up, her potassium level was normal, blood pressure target values achived, serum cortisol levels 610 nmol/l at 0800 h (after a regular Hydrocortisone dose) and 48 nmol/l at 0400 h, ACTH 4.8 pmol/l. Afterwards, she was referred to abdominal surgeon who performed total colectomy with ileo-recto anastomosis.Currently, the patient is stable, a hypothalamic-pituitary-adrenal axis is recovered: morning serum cortisol of 510 nmol/l and ACTH 31 pmol/l. Screening for ARMC5 mutations in first-degree relatives is advised.
Conclusion: Genetic testing for ARMC5 mutations might result in earlier identification and better management of Cushing syndrome. A prospective follow-up will allow better insight of the possible development of multiple tumor syndromes in these patients.
18 - 21 May 2019
European Society of Endocrinology