ODP648 MEN1 vs MEN4: when we cannot find a mutation

Abstract

MEN1 is an autosomal dominant syndrome characterized by involvement of several endocrine and non-endocrine organs. The most common endocrine organs that are affected include pituitary, parathyroid, and/or pancreas. In 10-30% of patients, no germline mutations in the menin gene are identified, presenting a diagnostic challenge. This case raises the question of possible MEN4 syndrome, which shares a similar phenotype to MEN 1 with germline mutation in CDKN1B. Clinical case 59 y/o female with PMH HTN, obesity, hypothyroidism initially presented to our clinic in 2018 for evaluation of hypercalcemia. She prior was seen in 2005 for evaluation of prolactinoma by outside endocrinologist but was lost to follow up. Per history, she had a pituitary MRI in 1991 for work up of amenorrhea and found to have prolactinoma. She was placed on bromocriptine at that time; after repeat pituitary MRI and prolactin levels were found to be normal, bromocriptine was discontinued in 2019 but then restarted a few months later due to uptrending prolactin level. During the visit with us, work up for her hypercalcemia included calcium of 11. 0 mg/dL and PTH level of 93 pg/mL with normal albumin, vitamin D, and renal function. Patient had a negative sestamibi scan but was found to have a 10 mm×5 mm×12 mm enhancing nodule along the left thyroid gland and along left lateral margin of esophagus, suggesting parathyroid adenoma. She subsequently underwent successful left inferior parathyroidectomy in July 2019 with normalization of calcium and PTH levels. No other parathyroid was found to be enlarged. Given her pituitary and parathyroid adenoma, she was sent for genetic testing; she was evaluated for 7 gene variants and all were found negative including MEN1, CDKN1B, GNA11, AP2S1, CASR, CDC73, and RET. Of note, she has no family history of MEN1 or any endocrine tumors. However, further testing was still performed to evaluate for a pancreatic neuroendocrine tumor including CT abdomen, gastrin, C peptide, chromogranin-A, glucagon, VIP, and 5-HIAA. Her initial testing came back normal including normal CT abdomen in 2020. However, her most recently lab results in 2021 revealed an elevated gastrin level of 124 pg/mL and uptrending chromogranin A of 262 ng/mL (<=93), the diagnosis of gastrinoma was confirmed and PPIs were started. Discussion This case highlights the importance of continued surveillance in patients with multiple endocrine organ involvement or neoplasia despite negative genetic testing; it also supports the likelihood of unidentified mutations given the improbable chance this patient has 3 independent endocrine tumors. Possibilities including missed germline mutations on testing or phenocopies. This patient likely has an upstream mutation that was not identified and could represent either MEN1 vs MEN4 Presentation: No date and time listed