左旋甲状腺素钠治疗先天性甲状腺功能减退症的初始剂量研究

目的 探讨先天性甲状腺功能减退症(CH)左旋甲状腺素钠(L-T_4)替代治疗的初始剂量.方法对筛查确诊的CH患儿分为A(n=36)、B(n=51)、C(n=40)3组,分别采用L-T_4 10、8和6 μg·kg~(-1)·d~(-1) 3种不同的初始剂量治疗,分别在治疗后第2周、4-6周、8～12周复查血清TSH、T_4和FT_4水平,根据结果进行L-T_4剂量的个体化调整.12周后每3个月复查1次,随访2年.期间定期进行患儿体格发育评价,甲状腺超声检查、骨龄检测和智能发育测定.结果127例患儿治疗2周,(1)TSH水平,A、B组迅速下降至正常范围(1.3±1.5)mU/L和(3.7±5.6)mU/L],两组间差异无统计学意义(P=0.28),A组中8例(22.2%)TSH下降到0.5 mU/L以下;C组TSH均未降至正常(11.4±16.5)mU/L],与A、B组比较有显著性差异(P<0.01),其中10例(25.0%)TSH>10 mU/L,平均值为(34.0±19.2)mU/L.(2)T_4、FT_4水平迅速提高,A组有9例(25.O%)T_4>250 nmol/L;11例(30.6%)FT_4>45 pmol/L,达到正常值高限的1.5倍,并出现高甲状腺素血症,13例(36.1%)患儿分别表现腹泻、烦躁、多汗、哭吵不安等甲状腺功能亢进的临床症状.治疗12周后3组间TSH、T_4和FT_4水平无显著差异,L-T_4剂量也无显著差异.治疗随访2年,127例身高、体重均达到相应年龄的正常范围(x±s);腕部骨龄成熟程度达到相应年龄,3组无显著性差异;智力发育达到正常水平,3组间差异无统计学意义(均P>0.05).结论L-T_4初始剂量(8.0±0.5)μg·kg~(-1)·d~(-1)是我国先天性甲状腺功能减退症初始治疗比较安全、合理、有效的剂量.CH替代治疗时,L-T_4剂量必须个体化,保持甲状腺功能与其年龄相匹配的水平,应能保证其体格和智能的正常发育.

Optimal initial dose of levothyroxine for treatment of congenital hypothyroidism

Objective The purpose of this study was to investigate the optimal initial dose of levothyroxine(L-T_4)for treatment of congenital hypothyroidism(CH).Methods One hundred and twenty-seven CH infants were assigned to A(n=36),B(n=51),and C(n=40)groups.Different initial doses were given to the patients,10 μg·kg~(-1)·d~(-1) for A group,8 μg·kg~(-1)·d~(-1) for B group and 6 μg·kg~(-1)·d~(-1) for C group.Blood TSH,L and FT_4 Ievels were determined at 2 weeks,4-6 weeks and 8-12 weeks after medication.L-T_4 dose was adiusted individually according to the blood hormone levels.Thyroid hormone levels were rechecked every three months after 12 weeks of medication.All the patients were followed up for 2 years,with regular assessment of growth,development,and thyroid ultrasonography.Results After 2 weeks'medication,TSH levels in both A and B groups were reduced to reference range(1.3±1.5)mU/L and(3.7±5.6)mU/L].No difference was found between the 2 groups(P=0.28).Eight patients(22.2%)in the A group had a reduced TSH level to less than0.5 mU/L.TSH level in the C group remained abnormal(11.4±16.5)mU/L]and significant difierence was observed when compared with those in the B and C groups(P<0.01).10 patients in the C group had a TSH level more than 10 mU/L(34.0±19.2)mU/L].T_4 and FT_4 levels in all the three groups increased markedly.9patients(25.0%)in the A group had T_4 level more than 250 nmol/L,and 11 patients(30.6%)showed hyperthyroxinemia with FT_4 level more than 45 pmol/L(1.5 folds of upper limit of the reference range).13patients in the A group showed clinical symptoms of hyperthyroidism such as diarrhea,irritability,sweating,cry,and so on.After 12 weeks medication,no significant difference was found in blood TSH,T_4,and FT_4 levels among the 3 groups.Also no difference was observed in adjusted L-T_4 dosages among the 3 groups.After 2-year follow-up,clinical examinations including height,weight,bone age,and mental development were all normal for the patients.No differences were found among the 3 groups(all P>0.05).Conclusions Optimal initial dosage of L-T_4 for CH treatment in our country is(8.0±0.5)μg·kg~(-1)·d~(-1) which is proved to be safe and effective.L-T_4dosage should be individualized.To maintain the thyroid function in the age-matched normal reference will lead to normal growth and development.