Endocrine Abstracts

A 34-year-old was referred for a second opinion regarding his incidental mild hypercalcemia ranging between 2.56 mmol/l and 2.88 mmol/l, with a corresponding PTH ranging between of 3.3 pmol/l and 6.8 pmol/l (laboratory reference range 1.3-9.3 pmol/l). He did not have a history of renal calculi or fractures. He reported chronic recurrent diarrhoea, weight loss, low mood and chronic headache. There was no known family history of calcium disorders. His examination did not reveal abnormalities. His 24-h calcium creatinine ratio was 0.02 and 24 h urinary calcium was high at 15.91 mmol/24 h. A previous ultrasound of the neck did not identify parathyroid lesion. Familial hypocalciuric hypercalcaemia was clinically unlikely due to the hypercalciuria. A germline mutational analysis was carried out to rule out monogenic causes of hyperparathyroidism using the available eight gene panel for monogenic causes of hypercalcaemia. He was found to be heterozygous for MEN1 mutation, c.758C>T p.(Ser253Leu), which is a known pathogenic mutation. The variant has been reported with hyperparathyroidism and MEN1, with a biallelic loss being reported in a sporadic parathyroid tumour. The proband’s first degree relatives have been offered mutational analysis. Imaging and biochemical investigations so far have not revealed other tumours or endocrine abnormalities associated with MEN1. Mutational analysis is associated with a low yield of positivity in isolated primary hyperparathyroidism. In this case, the single pointer of a likely underlying inherited cause is the relatively young age at presentation. There are numerous points of discussion in this case including the approach to diagnosis of hypercalcaemia in a person with a fluctuating level of calcium, with a low unsuppressed PTH and the indications for mutational analysis to aid diagnosis. Here, the diagnosis of MEN1 is likely to be transformative to his outcome and his affected first-degree relatives.