PDF(Pubmed)
Abstract：
Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A case involving a heterozygous pathogenic variant of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been previously reported. A 23-year-old woman presented with fatigue and was found to be hypercalcemic at 13.8 mg/dL [reference range, 8.4-10.2 pg/mL]. Her parathyroid hormone (PTH) was 62 pg/mL [reference range, 19-88 pg/mL] and 1,25-DHVD was elevated to 242.7 pg/mL [reference range, 18-72 pg/mL]. Other laboratory workup was unrevealing. She had a bone scan, whole body CT scan, and thyroid ultrasound that were normal. Her 25-hydroxy-vitamin D to 24,25-dihydroxy-vitamin D ratio was elevated at 25.18 (normal, < 25). Because of concern for primary hyperparathyroidism, she was referred to an endocrine surgeon and underwent a parathyroidectomy with the removal of a 3.5-gram adenoma. Pathology showed a parafibromin-deficient parathyroid neoplasm. Genetic testing demonstrated a heterozygous pathogenic variant in CYP24A1. Three weeks after surgery, PTH was 14 pg/mL (1.48 pmol/L), calcium and 1,25-DHVD normalized. In summary, we report a case where a patient with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism exacerbated by an underlying heterozygous pathogenic variant in CYP24A1.
摘要：
CYP24A1的致病变体与高钙血症有关，这是由于24-羟化酶分解1,25-二羟维生素D（1,25-DHVD）的能力被破坏。以前尚未报道一例涉及CYP24A1杂合子致病变种和原发性甲状旁腺功能亢进导致严重高钙血症的病例。一名23岁的女性出现疲劳，被发现在13.8毫克/分升[参考范围，8.4-10.2pg/mL]。她的甲状旁腺激素（PTH）为62pg/mL[参考范围，19-88pg/mL]和1,25-DHVD升高至242.7pg/mL[参考范围，18-72pg/mL]。其他实验室检查没有透露。她做了骨骼扫描,全身CT扫描,和正常的甲状腺超声。她的25-羟基维生素D与24,25-二羟基维生素D的比率升高至25.18（正常，<25).由于担心原发性甲状旁腺功能亢进，她被转诊至内分泌外科医生,并接受了甲状旁腺切除术,切除了3.5克腺瘤.病理显示纤维旁蛋白缺乏的甲状旁腺肿瘤。遗传测试表明CYP24A1中存在杂合致病变异。手术三周后,PTH为14pg/mL（1.48pmol/L），钙和1,25-DHVD正常化。总之,我们报道了一例有严重症状的高钙血症患者被发现患有原发性甲状旁腺功能亢进症,其原因是CYP24A1中潜在的杂合子致病变异体加重.
