Zavatta Guido, Clarke Bart L
G Zavatta, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
B Clarke, Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, United States.
Endocr Connect. 2020 Sep 1;9(10):R229-40. doi: 10.1530/EC-20-0366.
The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] was approved by the FDA in January 2015. Since the approval of rhPTH(1-84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.
慢性甲状旁腺功能减退症的首个辅助激素疗法——重组人甲状旁腺激素(1-84)[rhPTH(1-84)]于2015年1月获美国食品药品监督管理局(FDA)批准。自rhPTH(1-84)获批以来,科学界和制药公司对治疗该疾病的其他药物的兴趣与日俱增。由于多种原因,补充钙和活性维生素D、按需补充镁以及偶尔使用噻嗪类利尿剂的传统疗法仍是主要治疗手段,而内分泌科医生和患者不断受到传统治疗局限性的挑战。血清钙波动、尿钙增加、高磷血症以及一系列限制心理和身体功能的症状常与传统疗法相关。了解传统治疗和激素疗法在药代动力学和药效学方面的作用机制是有效管理慢性甲状旁腺功能减退症的关键。关于甲状旁腺激素辅助疗法在预防或延缓甲状旁腺功能减退症经典并发症(如慢性肾病、含钙肾结石、白内障或基底节钙化)的发生和进展方面的有效性,仍存在多个问题。多项研究表明替代治疗期间生活质量有所改善。本综述将讨论慢性甲状旁腺功能减退症治疗目前面临的临床和研究挑战。