Endocrine Abstracts

Introduction: Primary hyperparathyroidism is the commonest manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome, which is caused by germline mutations on MEN1. Loss of functional menin leads to tumour development through unregulated cell division. The MEN1 c.941G>C, p.(Arg314Pro) variant has previously been thought to co-segregate in one family with MEN1 with tumours of parathyroid glands and endocrine pancreas.

Clinical Case: A 37-year-old man had undergone surgery removing three of four parathyroid glands due to primary hyperparathyroidism. Histopathology demonstrated parathyroid hyperplasia. More than a decade later, he was found to have bilateral nephrolithiasis with ionised calcium of 1.35 mmol/l (ref 1.15-1.33 mmol/l) and PTH of 6.0 pmol/l (ref 1.6-6.9 pmol/l). Pituitary and pancreatic hormones were unremarkable. The patient’s mother had previously twice undergone surgery to remove parathyroid glands due to primary hyperparathyroidism. The patient’s brother had four parathyroid glands removed due to hypercalcaemia. The patient’s son had hypercalcaemia with nephrolithiasis. Genetic sequence analysis identified that the patient had a heterozygote missense variant on MEN1 c.941G>C, p.(Arg314Pro) and the same mutation was found in his mother and brother. Screening of the pituitary and pancreas in all affected individuals have not shown any other manifestations of MEN1.

Clinical Lesson: A novel heterozygote mutation on MEN1 is now known to cause familial primary hyperparathyroidism, without the other manifestations of MEN1. Thus, one must consider that there may be other variants on MEN1 which lead to isolated tumour development in the pituitary gland or pancreas. Genetic sequence analysis should be considered in patients with a family history of hypercalcaemia or other isolated manifestations of MEN1.