Endocrine Abstracts

CYP24A1 gene encodes 24-hydroxylase that inactivates 1-25-OHvitaminD. Mutations induce infantile hypercalcemia, with high 1-25-OHvitaminD, contrasting with low PTH levels. Adult phenotypes are not well known yet. We report two cases of post-surgical persistent hypercalcemia, related to CYP24A1 mutations. Two unrelated patients, a 40-year-old female (#1) and 54-year old male (#2), were referred for nephrolithiasis, enthesis and hypertension in both, associated to nephrocalcinosis in #1, osteopenia in #2. Before surgery, their respective biological characteristics were as follows: (#1/#2) calcemia: 139/111 mg/l (n: 85–105); phosphatemia: 28/27 mg/l (n: 25–45); PTH: 92/22 pg/ml (n: 15–68); 25-OHvitaminD: 38/26 ng/ml (n: 30–80); 1–25-OHvitaminD: 120/56 pg/ml (n: 18–70); creatinine: 12/15 mg/l (n: 7–10); calciuria: 434/400 mg/24 h (n: 60–300). In #1, cervical echography and Tc-MIBI-scintigraphy were negative but tomodensitometry showed a left inferior parathyroid hypertrophy. Surgery did not enable to find the pathological gland leading to subtotal parathyroïdectomy, left thyroid lobo-isthmectomy and thymectomy. Pathological examination showed hyperplasia of the two superior parathyroid glands and three papillary thyroid microcarcinomas (PTC). In #2, cervical echography, scintigraphy and tomodensitometry showed a 10 mm right parathyroid lesion corresponding to an adenoma after surgery. Calcium levels remained high post-surgery in both with a partial efficacy of cinacalcet. A compound heterozygote mutation of CYP24A1 (#1: p.Cys380Arg/p.Leu409Ser; #2: c.13DUPc.1/27GA in exons 7–8) were identified. Conclusion i). CYP24A1 phenotype can evolve with time from hypercalcemia with low PTH to a biological profile suggesting hyperparathyroidism. ii). Whatever morphological investigations, surgery is ineffective. iii). An increased frequency of PTC has been reported. iv). Increased 1-25OH and 25OHvitaminD without supplementation should suggest the diagnosis, which can be confirmed by investigating CYP24A1 gene mutation. 5. Sun and vitaminD eviction, hyperhydratation±cinacalcet or ketokonazole are recommended.