Endocrine Abstracts

Background: Mutation in the CYP24A1 gene can have variable phenotypes including infantile hypercalcemia and adult-onset hypercalcemia, hypercalciuria, nephrocalcinosis, or nephrolithiasis. CYP24A1 gene mutation is a rare but important cause of PTH-independent hypercalcemia.

Case Presentation: We describe a case of a 67-year-old gentleman who presented with lethargy, fatigue and weight loss. He was found to have PTH-independent hypercalcemia with acute renal impairment. His biochemistry was as follows: adjusted calcium of 3.13 mmol/l (Reference Range (RR) 2.20-2.60)), PTH 0.7 pmol/l, phosphate 1.32 mmol/l, Vitamin D 134 nmol/l and creatinine 249 umol/l. His past medical history included Type 1 diabetes. At the time, he was taking over-the-counter vitamin D3 spray (up to 36,000 units/weekly), which he started during the Covid pandemic. He was initially managed with intravenous fluids and advised to stay off any vitamin D supplementation and keep well hydrated upon discharge. He was extensively investigated but no malignancy was identified. During the follow-up, his calcium level normalised and his renal function improved. His PTH-related peptide level was reassuringly undetectable but 1,25(OH)2D3 level was inappropriately high at 158 nmol/l (RR 55-139). A 24-hour urine calcium output was raised at 13.3 mmol/day (NR 2.5-7.5). Genetic analysis for a possible CYP24A1 mutation was requested but no mutation was identified. As our level of suspicion remained high, we went on to measure the level of 24,25 dihydroxy vitamin D. A raised 1,25:24,25 dihydroxy vitamin D ratio of 64 was found in keeping with 24- hydroxylase deficiency.

Discussion: The COVID era saw the zealous use of vitamin D supplements which can potentially unmask CYP24A1 mutations with milder phenotypes. The use of a 1, 25:24, 25 dihydroxy vitamin D ratio can be a useful diagnostic tool in patients suspected of CYP24A1 mutations, with negative genetics.