左甲状腺素治疗先天性甲状腺功能减退症儿童的最佳初始剂量

Optimal initial dose of levothyroxine replacement therapyin children with congenital hypothyroidism

目的:回顾分析先天性甲状腺功能减退症(congenital hypothyroidism,CH)儿童的发病情况及治疗效果,探讨CH患儿左甲状腺素(levothyroxine,LT4)替代治疗的最佳初始治疗剂量。方法:收集1987年至2018年上海市儿童医院新生儿筛查中心随访并接受LT4治疗的231例CH患儿,根据首次甲状腺功能的血游离甲状腺激素(free thyroxine,fT4)水平分为3组,即轻度CH组(60例)、中度CH组(97例)、重度CH组(74例)。在不同分组内进行剂量效应分析,利用Poisson回归分析各组内LT4不同初始治疗剂量下随访2岁内的用药调整情况。结果:(1)新生儿筛查促甲状腺激素(thyroid stimulating hormone,TSH)水平、首次召回后静脉血fT4水平、甲状腺发育情况对治疗后患儿TSH水平的影响差异有统计学意义(P<0.05);(2)治疗后2周~1个月,轻度CH组患儿LT4初始治疗剂量在6~8μg·(kg·d)^(-1)、中度CH组患儿初始治疗剂量在>8~10μg·(kg·d)^(-1)时TSH恢复正常比例较高(分别为70.37%、70.00%),fT4均可在该年龄段参考值的正常范围内或高于参考值范围,2岁内调整用药的次数也相对较少(分别为22.30%、20.09%),差异具有统计学意义(P<0.05)。结论:LT4治疗CH有效,根据疾病程度,轻度CH患儿和中度CH患儿的最佳初始治疗剂量依次为6~8μg·(kg·d)^(-1)和>8~10μg·(kg·d)^(-1);对于重度CH患儿可适当提高LT4初始治疗剂量[>10μg·(kg·d)^(-1)],以尽快使TSH、fT4恢复至正常。

Objective:To analyze the incidence and treatment of congenital hypothyroidism(CH)to explore an optimal initial replacement therapy dose of levothyroxine(LT4)for CH.Methods:231 children with CH,who were followed-up and treated with LT4 at the Neonatal Screening Center in Children s Hospital of Shanghai during 1987 to 2018,were enrolled and divided into three groups according to the initial level of free thyroxine(FT4):mild CH group(n=60),moderate CH group(n=97)and severe CH group(n=74).The dose-effect curves were performed in different groups,after which Poisson regression was used to analyze the adjustments of LT4 within 2 years under different initial doses in each group.Results:(1)The effects of neonatal screening TSH concentrations,the first serum free thyroxine(fT4)concentrations and thyroid ultrasonography on TSH level after treatment were statistically significant(P<0.05).(2)For the children in the mild CH group and the moderate CH group who received an initial therapeutic doseof about 6-8μg·(kg·d)^(-1) and 8-10μg·(kg·d)^(-1) respectively,the proportion of restoration of TSH to normal level was high(70.37%and 70.00%,respectively)after treatment for 2 weeks to 1 month,and fT4 could be within or higher than the age-specific reference range,and the adjustments of LT4 were less during the first 2 years(22.30%in mild CH and 20.09%in moderate CH).The difference was statistically significant(P<0.05).Conclusion:LT4 is effective in treating CH.According to the severity of CH,6-8μg·(kg·d)^(-1) for mild CH and>8-10μg·(kg·d)^(-1) for moderate CH is an optimal initial dose.Infants with severe CH may be treated with a higher initial dose[>10μg·(kg·d)^(-1)]to maintain TSH and fT4 concentration in the age-specific reference range as soon as possible.