Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Koyang-si, Gyeonggi-do, Republic of Korea.
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Koyang-si, Gyeonggi-do, Republic of Korea.
Endocrinology. 2020 Oct 1;161(10). doi: 10.1210/endocr/bqaa145.
Postsurgical hypoparathyroidism is the most common complication of thyroid surgery. Conventional therapy with high-dose calcium and vitamin D can correct hypocalcemia but can increase the risk of hypercalciuria, renal stones, or ectopic calcification. The aim of the present study was to investigate the efficacy of a calcium-sensing receptor antagonist, also called a calcilytic (AXT914), in rat models of postsurgical hypoparathyroidism. Two postsurgical hypoparathyroidism rat models were made by hemi-parathyroidectomy or total parathyroidectomy with autotransplantation in 10-week-old female Wistar rats. AXT914 or vehicle was administered orally for 2 to 3 weeks. Serum PTH, calcium, and phosphorus levels, and the urinary excretion of calcium were measured. Autotransplanted parathyroid tissues were collected and examined histologically. In the hemi-parathyroidectomy model, the oral administration of the calcilytic AXT914 (5 and 10 mg/kg) for 2 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels and urinary calcium excretion. In the total parathyroidectomy with autotransplantation model, the oral administration of AXT914 (10 mg/kg) for 3 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels. The serum PTH and calcium levels increased by AXT914 were maintained for 1 week, even after discontinuation of the drug. In conclusion, AXT914 increased PTH secretion in rat models of postsurgical hypoparathyroidism, thereby correcting abnormal calcium and phosphorus homeostasis. Furthermore, AXT914 improved the functional recovery of autotransplanted parathyroid tissues.
手术后甲状旁腺功能减退症是甲状腺手术后最常见的并发症。高剂量钙和维生素 D 的常规治疗可以纠正低钙血症，但会增加高钙尿症、肾结石或异位钙化的风险。本研究旨在研究钙敏感受体拮抗剂（也称为calcilytic，AXT914）在手术后甲状旁腺功能减退症大鼠模型中的疗效。通过半甲状旁腺切除术或全甲状旁腺切除术加自体移植在 10 周龄雌性 Wistar 大鼠中建立了 2 种手术后甲状旁腺功能减退症大鼠模型。AXT914 或载体通过口服给药 2 至 3 周。测量血清 PTH、钙和磷水平以及尿钙排泄量。收集自体移植甲状旁腺组织并进行组织学检查。在半甲状旁腺切除术模型中，calcilytic AXT914（5 和 10mg/kg）口服给药 2 周可增加血清 PTH 和钙水平，降低血清磷水平和尿钙排泄量。在全甲状旁腺切除术加自体移植模型中，AXT914（10mg/kg）口服给药 3 周可增加血清 PTH 和钙水平，降低血清磷水平。AXT914 增加的血清 PTH 和钙水平在停药后 1 周仍保持不变。总之，AXT914 增加了手术后甲状旁腺功能减退症大鼠模型中 PTH 的分泌，从而纠正了异常的钙磷平衡。此外，AXT914 改善了自体移植甲状旁腺组织的功能恢复。
