长期延误治疗的甲状腺功能减低症患儿的追赶生长

Catch-Up Growth of Children with Longstanding Untreated Hypothyroidism

目的研究长期延误治疗的甲状腺功能减低症(甲减)患儿治疗后身高增长的规律及青春期对其身高的影响,探讨使用促性腺激素释放激素拟似物(GnRHa)和生长激素(GH)治疗辅助生长的可能性。方法分析28例长期被忽视(3a以上)的甲减患儿的追赶生长,其中青春前期13例(A组),青春期诊断并开始治疗15例(B组)。治疗过程中每3个月门诊随访1次,监测患儿身高、体质量、性发育情况、骨龄、血清甲状腺功能等指标。在左旋甲状腺素治疗的基础上,应用GnRHa和GH联合治疗2例长期延误治疗且已进入青春期的患儿。结果2组患儿初诊时均有明显的生长落后、骨龄落后。A组年龄(7.1±2.0)岁,骨龄(3.0±1.5)岁,身高标准差评分(HTSDS)为-3.89±1.29;B组开始治疗的年龄(14.3±1.6)岁,骨龄(5.6±2.3)岁,HTSDS-5.55±1.38。2组靶身高(TH)比较无差异。治疗第3年末,A组HTSDS提高至-1.12±1.14,B组上升至-1.94±1.39;治疗后2组患儿骨龄改变3a依次为A组(2.5±0.5)岁.a-1、(1.6±0.5)岁.a-1、(1.4±0.6)岁.a-1;B组分别为(5.2±1.8)岁.a-1、(2.4±1.0)岁.a-1、(2.6±0.8)岁.a-1,各年骨龄的加速生长B组显著快于A组(Pa<0.01),尤其第1年在年生长速率相近的情况下,B组所消耗的骨龄较A组多3岁。A组成人期终身高(FH)SDS为-0.40±0.99,达到其TH范围(-0.12±0.77);B组-1.85±1.18,未达到其TH范围(0.18±0.84)。2例长期被忽视至青春期方开始治疗的甲减患儿用GnRHa和GH联合治疗2a余,达到其TH。结论童年期开始治疗的甲减患儿的追赶生长是完全的。长期被忽视至青春期方诊断并开始治疗的甲减患儿的追赶生长不完全,耽误治疗的时间越长,丢失的身高越多,追赶的难度越大。建议联合使用GnRHa和GH改善这种不完全追赶生长。

Objective To analyze the catch-up growth of children with longstanding untreated hypothyroidism and to assess whether catch-up growth is complete and the use of gonadotropin releasing hormone agonist（GnRHa） and growth hormone（GH） is feasible in longstanding untreated and puberty-onset substitution hypothyroidism.Methods Catch-up growth was analyzed in 28 cases with hypothyroi-dism[13 prepubertal children（group A） with hypothyroidism and 15 pubertal children（group B）].During the period of treatment,the clinical parameters including height（HT）,weight,pubertal stage,bone age were documented every 3 months.The serum levels of thyroidtropin,tetraiodotyrosine and triiodotyrosine were monitored using immunofluorescence assay or radioimmunoassay.GnRHa and GH were used in addition to L-thyroxine in two longstanding untreated and puberty-onset substitution hypothyroidism patients.Results Two groups presented with significant growth retardation and bone age delay.The prepubertal children with hypothyroidism started treatment at the age of （7.1±2.0） years,bone age （3.0±1.5） years and a height standard deviation score（HT SDS）（-3.89±1.29）,while group B with hypothyroidism at the age of （14.3±1.6） years,bone age （5.6±2.3） years and a HT SDS of-5.55±1.38.There was no target height difference between 2 groups.At the end of the 3rd year,HT SDS of group A advanced to-1.12±1.14 and group B to-1.94±1.39.In group B,bone age progression was （5.2±1.8） years·a-1,（2.4±1.0） years·a-1,（2.6±0.8） years·a-1,faster than （2.5±0.5） years·a-1,（1.6±0.5） years·a-1,（1.4±0.6） years·a-1 in group A during the 1st,2nd and 3rd year（Pa0.01）,respectively.Especially in the first year,group B achieved the similar HT velocity compared with group A but cost 3 more years of bone age.Adult final height（FH） of group B reached a HT SDS of-1.85±1.18,not within their range（TH 0.18±0.84）,while group A （-0.40±0.99） reached their TH（-0.12±0.77）.Two years of combined use of GnRHa and GH in 2 cases of hypothyroidism starting to be treated at puberty improved their adult height to a HT SDS,both within their TH.Conclusions Catch-up growth in childhood onset hypothyroidism is complete,but in longstanding untreated and puberty-onset substitution hypothyroidism children is incomplete.GnRHa and GH treatment are needed to improve this incomplete growth and increase the TH.