SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome

Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B. Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology. The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l (