Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing syndrome and in 2555% of cases is caused by mutations in ARMC5 gene. A 37 y.o. female was referred to our center with a diagnosis of ACTH-independent Cushing syndrome. Laboratory testing confirmed endogenous hypercortisolism (urinary free cortisol 5063.5 nmol/24 h (60413), midnight salivary cortisol 56.6 nmol/l (0.59.4), midnight serum cortisol 1427 nmol/l (46270). ACTH level was 1 pg/ml (766). Adrenal CT scan showed that adrenals were enlarged and their structure was heterogeneous due to numerous nodes ranging in size from 12 to 36 mm; the length of the right adrenal gland was 9.3 cm, the left - 8.9 cm, which was consistent with PBMAH. Bilateral adrenalectomy was performed as the treatment of choice. Morphologic examination confirmed macronodular adrenal hyperplasia. Biochemical testing also revealed increased serum calcium (total calcium 2.542.61 (2.152.55), ionized 1.24 mmol/l (1.031.29) and increase PTH 70.44 pg/ml (1565)) enabling to diagnose primary hyperparathyroidism. Parathyroid ultrasound revealed enlarged upper right parathyroid gland 0.8×0.5×0.3 cm. Six months after adrenalectomy hypercalcemia persisted: total serum calcium 2.682.78 mmol/l, ionized serum calcium 1.221.28 mmol/l. No renal impairment, kidney stones or decreased bone mineral density were detected, thus dynamic control of primary hyperparathyroidism was chosen. The patients family history was remarkable for the presence of Cushing syndrome and PBMAH in the patients mother. Due to genetic heterogeneity of PBMAH whole-exome sequencing was performed, which revealed a heterozygous mutation in exon 6 of ARMC5 gene p.R898W (c.2692C>T) (NM_001105247). The mutation has already been described in patients with PBMAH and Cushing syndrome. Mutations in ARMC5 have been described in patients with concomitant meningiomas but not with primary hyperparathyroidism. Whether mutations in ARMC5 gene are associated with parathyroid tumor development is yet to be determined.
18 - 21 May 2019
European Society of Endocrinology