A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism.

A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism.
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每日一次与每日两次甲状旁腺激素 1-34 治疗甲状旁腺功能减退症的随机、交叉试验。

DOI:
10.1210/jcem.83.10.5185
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发表时间:
1998
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
G. Cutler
G. Cutler
中科院分区:
--
文献类型:
--
作者:
K. Winer;J. Yanovski;Babak Sarani;G. Cutler

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每日一次皮下注射 PTH 1-34 可使甲状旁腺功能减退症患者的平均血清和尿钙水平正常化;然而,每日一次的 PTH 在 12 小时后对血清钙的影响逐渐减弱,使得某些患者的血清钙水平降至正常范围以下。每日一次 PTH 还会导致骨转换显着增加,骨形成和吸收标志物持续增加。为了验证每日两次 PTH 方案比每日一次方案能产生更多生理控制的假设,我们在 17 名患有甲状旁腺功能减退症的成年受试者中进行了一项持续 28 周的随机交叉试验。每个 14 周的研究组分为 2 周的住院剂量调整阶段和 12 周的门诊阶段。调整 PTH 剂量(每天 0900 小时皮下注射一次,或每天两次,一剂在 0900 小时,另一剂在 2100 小时),以将血清和尿钙维持在或接近正常范围。在一天的后半段(12-24 小时),每天两次 PTH 比每天一次 PTH 更能有效地增加血清钙和镁水平。在患有钙受体突变 (CaR) 的患者中,每天一次 PTH 可以使尿钙正常化,前提是血清钙保持在正常范围以下的水平。然而,每日两次 PTH 治疗使 CaR 患者的平均血清钙水平较高,而尿钙排泄量没有显着增加,并且 CaR 与获得性或特发性甲状旁腺功能减退症患者之间的血清或尿钙水平没有显着差异。因此,对于 CaR 患者来说,每天两次 PTH 治疗是更好的治疗方案,可以克服高钙尿倾向,同时产生接近正常水平的血清钙。每日两次方案的每日总 PTH 剂量显着降低(每日两次 46+/-52 对比每日一次 97+/-60 微克/天,P < 0.001)。我们得出的结论是,每日两次 PTH 方案可有效治疗甲状旁腺功能减退症,并以较低的每日 PTH 总剂量减少血清钙水平的变化。
Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTH also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, we performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range. During the second half of the day (12-24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalciuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46+/-52 vs. once daily 97+/-60 microg/day, P < 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose.
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