Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 1 syndrome (MEN1) is a hereditary autosomal dominant disorder caused by germline mutations in the MEN1 tumour-suppressor gene and is typically characterized by parathyroid adenomas, duodenopancreatic neuroendocrine tumors (NETs) and pituitary adenomas. Breast cancer has recently been identified as manifestation of MEN1 and female patients have early onset elevated breast cancer risk.

Case report: Female patient, 51 years old, with personal history of ovarian mucinous borderline tumour, breast cancer, recurrent typical carcinoid lung tumour (surgery in 2010 and 2015; pT1bN0) and myeloid chronic leukaemia, treated with 2nd line therapy (bosutinib). She was referred to the Endocrinology Department for PTH-dependent hypercalcemia: PTH 133.4 pg/mL (18–80 pg/mL) ionized calcium 1.33 mmol/L (1.19–1.26 mmol/L) and osteoporosis on dual energy x-ray absorptiometry (DEXA), with T-score at the lumbar spine -3.8. The patient had no family history of malignant neoplasms. She complained of mild dyspepsia and was taking pantoprazole 20 mg/day. Physical examination revealed several lipomas. MEN 1 syndrome was suspected, given the diagnosis of primary hyperparathyroidism (PHPT), carcinoid lung tumour and breast cancer. Genetic testing for MEN1 was positive and the workup revealed an increased prolactin 42.51 ng/mL (<25 ng/mL), normal IGF-1, with normal brain MRI; Chromogranin A was increased 280.3 ng/mL (<102 ng/mL) under treatment with pantoprazole, with normal gastrin and pancreatic polypeptide. Chest CT was normal and upper endoscopy showed no gastric NETs. Abdominal MRI showed bilateral adrenal nodules (12 and 6 mm), but no signs of pancreatic NETs. These nodules were proven to be non-functioning. It was decided not to perform surgery for PHPT, given the patient’s multiple comorbidities, the stable levels of calcium and stable T-score on DEXA, as well as increased risk of post-surgery hypoparathyroidism. She started treatment with alendronic acid 70mg/week, with good tolerability

Discussion: The clinical spectrum of MEN1 has evolved in recent years and breast cancer is now a proven MEN1-related tumour. It remains to be confirmed whether other neoplasias, namely leukaemia or ovarian tumours are part of this spectrum. There is also concern with increased risk of cell injury from ionizing radiation in these patients, who need serial imaging monitoring. Other challenges include identification of index cases and selection of tumours that need appropriate therapy or active surveillance.