SUN-058 - Multiple Endocrine Neoplasia Type 4 (MEN4) Associated with CDKN1B: Long-Standing Primary Hyperparathyroidism with Nonfunctioning Pituitary Adenoma and Surveillance Strategy

Introduction
Multiple endocrine neoplasia type 4 (MEN4) is a rare hereditary endocrine tumor syndrome caused by germline CDKN1B mutations. It overlaps phenotypically with MEN1, most commonly presenting with primary hyperparathyroidism and pituitary adenomas, while pancreatic neuroendocrine tumors are less frequent. Owing to limited reported cases, the natural history and optimal surveillance of MEN4 remain incompletely defined. We describe a patient with MEN4 presenting with long-standing primary hyperparathyroidism, osteoporosis, and an incidental pituitary lesion.
Case Presentation
A 66-year-old woman was referred for evaluation of primary hyperparathyroidism diagnosed eight years earlier, characterized by persistently elevated parathyroid hormone (PTH) and intermittent mild hypercalcemia. Her other past medical history is significant for invasive ductal carcinoma status post right total mastectomy. After her breast cancer diagnosis, she had genetic testing done which came back positive for CDKN1B gene mutation which can be associated with MEN4, a rare autosomal dominant disorder caused by germline (inherited) mutation in the CDKN1B gene. Family history was notable for acromegaly and meningioma in her mother. She experienced minimal hypercalcemia-related symptoms, reporting only mild urinary frequency and intermittent back pain attributed to a remote T11 vertebral fracture.
Laboratory testing demonstrated elevated PTH (139 pg/mL; reference 16–77 pg/mL) with high-normal serum calcium (10.1 mg/dL), and normal renal function. Pituitary hormone evaluation, including prolactin, IGF-1, cortisol, and ACTH, was normal. Gastrin levels were normal. CT neck identified a 0.9-cm left inferior parathyroid adenoma. Pituitary MRI revealed a 4.5-mm posterior pituitary lesion without hormonal hypersecretion. Abdominal MRI showed no pancreatic or adrenal lesions.
She was referred for parathyroidectomy and enrolled in MEN4 surveillance with abdominal MRI every 2.5 years and MRI pituitary every 5 years. Cascade genetic testing was recommended for at-risk family members.
Discussion
This case highlights the variable and often indolent presentation of MEN4. Primary hyperparathyroidism is the most common manifestation and may resemble sporadic disease, although skeletal complications can occur despite mild hypercalcemia. The presence of a nonfunctioning pituitary lesion is consistent with prior MEN4 reports. Given the lower prevalence of pancreatic neuroendocrine tumors compared with MEN1, surveillance strategies are largely extrapolated from MEN1 guidelines but may be individualized. Recognition of CDKN1B mutations enables tailored surveillance, informed surgical decision-making, and family risk assessment.

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