Callies F, Arlt W, Scholz H J, Reincke M, Allolio B
Department of Endocrinology, Medical University Clinic Würzburg, Germany.
Eur J Endocrinol. 1998 Sep;139(3):284-9. doi: 10.1530/eje.0.1390284.
There is no established therapeutic regimen for treatment of hypoparathyroidism during pregnancy. This is due particularly to uncertainty about the use of vitamin D or its analogues, as in animal experiments teratogenic side-effects have been reported. Nevertheless, vitamin D or its analogues are required to control tetany predisposing to abortion and preterm labour. We herein report the course of two pregnancies in a hypoparathyroid woman treated with calcitriol (1,25(OH)2D3). Additionally, we describe the outcome of pregnancy in ten women receiving calcitriol, reported to the Drug Safety Department (DSD), Hoffmann-La Roche AG. A 29-year-old hypoparathyroid woman receiving chronic treatment with calcitriol (0.25 microg/day) and calcium (1.5 g/day) was referred in the 6th week of her first pregnancy. Calcitriol was initially discontinued, but during the 20th week of pregnancy recurrent tetany occurred (serum calcium 1.74 mmol/l). Calcitriol (0.25 microg/day) was added, stabilizing serum calcium around 2.15 mmol/l with 1,25(OH)2D3 concentrations around 60 ng/l (normal range 35-80 ng/l). To maintain normocalcaemia the calcitriol dose was increased to 0.5 microg/day during the 33rd week and to 0.75 microg/day shortly before delivery of a healthy girl in the 3 7th week. During her second pregnancy calcitriol was given initially at a dose of 0.25 microg/day with further adaptation to 0.5 microg/day during the 20th and to 1.00 microg/day in the 31st week. Serum calcium and 1,25(OH)2D3 were continually within the lower normal range. She gave birth to another healthy girl during the 39th week. In eight of the ten pregnancies reported to the DSD no adverse effects of calcitriol (0.25-3.25 microg/day) were seen and healthy babies were delivered. In two retrospectively reported cases, serious adverse events were described: premature closure of the frontal fontanelle, and stillbirth in the 20th week due to complex fetal malformation respectively. However, in both cases the causative role of calcitriol administration remains highly questionable. We conclude that, during pregnancy, management of maternal hypoparathyroidism with calcitriol and calcium is feasible, if the 1,25(OH)2D3 concentrations are adapted to the physiological needs during pregnancy and serum calcium levels are kept in the lower normal range.
目前尚无针对孕期甲状旁腺功能减退症的既定治疗方案。这尤其归因于维生素D或其类似物使用的不确定性,因为在动物实验中已报道有致畸副作用。然而,维生素D或其类似物对于控制易引发流产和早产的手足搐搦是必需的。我们在此报告一名接受骨化三醇(1,25(OH)₂D₃)治疗的甲状旁腺功能减退症女性的两次妊娠过程。此外,我们描述了向霍夫曼 - 罗氏公司药物安全部(DSD)报告的10名接受骨化三醇治疗的女性的妊娠结局。一名29岁的甲状旁腺功能减退症女性,长期接受骨化三醇(0.25μg/天)和钙(1.5g/天)治疗,在其首次妊娠的第6周前来就诊。骨化三醇最初停用,但在妊娠第20周时出现反复手足搐搦(血清钙1.74mmol/L)。随后添加骨化三醇(0.25μg/天),血清钙稳定在2.15mmol/L左右,1,25(OH)₂D₃浓度在60ng/L左右(正常范围35 - 80ng/L)。为维持血钙正常,在第33周时骨化三醇剂量增加至0.5μg/天,并在第37周健康女婴出生前不久增加至0.75μg/天。在她第二次妊娠期间,最初给予骨化三醇剂量为0.25μg/天,在第20周进一步调整至0.5μg/天,在第31周调整至1.00μg/天。血清钙和1,25(OH)₂D₃持续处于较低正常范围内。她在第39周时又生下一个健康女婴。向DSD报告的10例妊娠中,有8例未观察到骨化三醇(0.25 - 3.25μg/天)的不良反应,且均分娩出健康婴儿。在另外两例回顾性报告的病例中,描述了严重不良事件:分别为前囟过早闭合以及因复杂胎儿畸形在第20周时死产。然而,在这两例中骨化三醇给药的致病作用仍极具疑问。我们得出结论,在孕期,通过骨化三醇和钙来管理母体甲状旁腺功能减退症是可行的,前提是1,25(OH)₂D₃浓度适应孕期的生理需求,且血清钙水平保持在较低正常范围内。