MON-LB059 A Family Reunion at the Geneticist's Office: Hypercalcemia as Presenting Symptoms of MEN1

Abstract

Background: MEN1 syndrome is an autosomal dominant disorder of the MEN1 gene, which encodes the tumor suppressor protein menin, characterized by primary hyperparathyroidism, pituitary and gastro-entero-pancreatic tract tumors. Patients typically present in the second decade of life with primary hyperparathyroidism. The diagnosis is made in 90% of patients by the fifth decade. Early recognition of MEN1 associated tumors through periodic biochemical and radiological surveillance allows for early intervention, leading to presumed reduction in morbidity and premature death related to metabolic effects and tumor metastases. Clinical Case: A 32yo female with GERD, PCOS, and type 2 diabetes presented with fatigue, anxiety, constipation and myalgia. Laboratory studies revealed corrected serum calcium 11.7 (n8.4-10.5) mg/dl, PTH 290 (n10-65) pg/ml, 25-hydroxyvitamin D 16 (n30-100) ng/ml. The patient presented to the ER 1 week after successful parathyroidectomy with paresthesia, myalgia, bone pain consistent with hungry bone syndrome. CT of the chest and abdomen revealed a 1.8 cm pancreatic mass. A subsequent endoscopic ultrasound-guided biopsy confirmed a NET. Biochemical hormone workup confirmed it was non-functional. MRI pituitary revealed an adenoma, and genetic testing confirmed a mutation in the MEN1 gene. Genetic testing was completed on the patient’s family members, confirming MEN1 in 1 of 3 siblings and 2 of 2 children. Subsequent surveillance efforts revealed an enlarging mass in her bronchial tree, concerning for bronchial carcinoid seen in MEN1. A transbronchial biopsy confirmed neuroendocrine proliferation. Lobectomy was completed, with pathology demonstrating a typical carcinoid tumor. Discussion: MEN1 patients are at increased risk of premature death where 30% of deaths is due to associated tumors. The mean age at the time of death for female patients with MEN1 was 46.8 years, compared to the age 75.6 years in the general population. The minimal surveillance program recommends annual measurement of serum biomarkers starting at age five, head MRI starting at age five and abdominal imaging starting at age 20. It should be noted there is a lack of data demonstrating mortality benefit of surveillance programs. In one study, surveillance was associated with significant radiation exposure, with mean lifetime risk of secondary malignancy at 0.49%. In contrast, clinical and genetic screening of at-risk patients allowed diagnosis of MEN1 in asymptomatic patients at a younger age, detection of tumors at earlier stages of growth, and reduction of metastasis and mortality compared to probands. This case presents an interesting development of what seemed to be a benign case of hypercalcemia, complicated by a hungry bone syndrome, followed by a diagnosis of MEN1 syndrome in this patient and her family members, effectively decreasing their likelihood of syndrome-related mortality. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.