Endocrine Abstracts

Bilateral Primary Macro nodular Adrenal Hyperplasia (BPMAH) is a rare cause of endogenous Cushing’s syndrome. The association with ARMC5 gene mutation was first described in 2013 and one recent series demonstrated 14% of BPMAH cases show germ-line pathological mutations in ARMC5 gene. The clinical phenotype of this condition is not fully described. There is a known association with meningioma.

Case 1: A 45-year-old woman with hypertension and diabetes was incidentally found to have bilateral adrenal masses on CT angiogram. Biochemistry showed Cushing’s (post-overnight dexamethasone cortisol 687 nmol/l; 48-hour 575 nmol/l) with suppressed ACTH. Low-dose metyrapone 250 mg tds, later 500 mg bd, achieved mean cortisol 187 nmol/l, weight loss and diabetes remission. Germ-line testing revealed ARMC5 mutation (p.Y549*). Long-term therapy continues. A brain MRI showed a petrous ridge meningioma which is managed conservatively.

Case 2: A 53-year-old woman with type 2 diabetes, poorly controlled hypertension and osteoporosis had bilateral adrenal masses discovered during tuberculosis therapy. Biopsy confirmed cortical hyperplasia. Cushing’s was demonstrated (9 am cortisol 500 nmol/l; post-1 mg dexamethasone 449 nmol/l; post-8 mg 607 nmol/l) with suppressed ACTH. Despite prior reported intolerance, low-dose metyrapone 250 mg tds produced excellent biochemical and clinical control, obviating adrenalectomy. Germline ARMC5 mutation (p.S458X) was confirmed; her brother had adrenal Cushing’s. Brain CT was normal; MRI is pending.

Discussion: These two cases of BPMAH due to ARMC5 mutation show effective long term medical control with relatively low dose metyrapone. These cases suggest this form of BPMAH might be particularly responsive to metyrapone, avoiding the need for unilateral or bilateral adrenalectomy. The cases are also a reminder to assess for meningioma in patients with the ARMC5 mutation.