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-东南大学学报医学版

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

单位：1. 上海交通大学医学院附属儿童医院/上海市儿童医院新生儿科, 上海 200062;
2. 中央民族大学药学院临床中药学教研室, 北京 100081;
3. 上海交通大学医学院附属儿童医院/上海市儿童医院新生儿筛查中心, 上海 200040

关键词：先天性甲状腺功能减退症左甲状腺素初始治疗剂量治疗效果

分类号：R582.2

出版年·卷·期（页码）：2024·43·第一期（118-124）

摘要：

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 6-8 μg·(kg·d)^-1 and 8-10 μg·(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,6-8 μg·(kg·d)^-1 for mild CH and >8-10 μg·(kg·d)^-1 for moderate CH is an optimal initial dose. Infants with severe CH may be treated with a higher initial dose[>10 μg·(kg·d)^-1] to maintain TSH and fT4 concentration in the age-specific reference range as soon as possible.

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