Endocrine Abstracts

A 33 year-old man was referred to the endocrine bone clinic following presentation with a 4 mm kidney stone and hypercalcaemia. Apart from mild fatigue, he had no other hypercalcaemic or concerning symptoms. He was not on any medications or supplements. He had a positive family history for kidney stones and reported that his grandmother had been noted to have hypercalcaemia in the past. There was significant consanguinity in his family. Examination was entirely normal while blood tests revealed intermittent hypercalcaemia between 2.50 and 2.83 mmol/l (2.2–2.6), with raised 24 h urinary calcium (7.8 mmol/24 h (2.5–7.5)). PTH was low at 0.3 pmol/l (1.6–7.2), with undetectable PTHrP (<1 pmol/l). 25OH-vitamin D was 83 nmol/l (70–150). Based on the concerning finding of hypercalcaemia with low PTH, cross-sectional imaging was performed which did not reveal any signs of malignancy or granulomatous disease. Therefore, further exploration of vitamin D metabolism was performed. This began with the finding of high-normal biologically active vitamin D (1,25(OH)₂-vitamin D 138 pmol/l (55–139)), and subsequent finding of a raised active:inactive (1,25:24,25(OH)₂-vitamin D ratio of 66 (7–30)). This suggested loss-of-function mutation in the CYP24A1 gene, which encodes the enzyme responsible for reducing activated vitamin D (1,25(OH)₂-vitaminD-24hydroxylase). Management included good fluid intake, low sun exposure, with low calcium and vitamin D intake. With these measures, his latest calcium is 2.53 mmol/l with an intentionally low 25OH-Vitamin D of 33.4 nmol/l. This case illustrates a rare but important cause of intermittent hypercalcaemia. This patient had increased active 1,25(OH)₂-vitamin D with low inactive 24,25(OH)₂-vitamin D resulting in hypercalcaemia when presented with a significant dietary calcium load (hence intermittent). This case also demonstrates a rare but important differential in patients presenting with the otherwise highly concerning combination of hypercalcaemia and low PTH. He is shortly planning a family and so genetic counselling will be of paramount importance.