不同年龄和青春发育阶段与青春期女性甲状腺功能指标参考区间的关联

Association of different ages and pubertal developmental stages with reference intervals of thyroid function indices in adolescent females

目的探讨青春期女性主要甲状腺功能指标与年龄、青春发育阶段的关联性以及与成人参考区间的差异。方法在2017年10—11月、2019年1—3月于上海市闵行区、江苏省海门市、浙江省玉环市、浙江省德清县各选定1所初中,将4所初中共791名女生纳入研究,对研究对象进行体格检查以及甲状腺激素水平检测;采用《青春发育事件自我评定量表》评价青春发育分期。分别于2年后随访,调查内容一致。评估11~15岁5个年龄组甲状腺功能水平,计算95%CI,采用混合线性模型分析年龄及青春期发育阶段对激素水平的影响。结果青春期女性促甲状腺激素(thyroid stimulating hormone,TSH)、游离三碘甲状腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(free thyroxine,FT4)的参考区间与成人存在较大差异,错分率为2.98%~5.17%。在校正了BMI、腰围后,年龄、青春发育分期以及年龄与青春发育分期的交互作用均存在统计学差异(P均<0.05),TSH水平在青春发育完成前受年龄影响较大,12岁组水平高于11岁组(P=0.0012)和13岁组(P<0.0001);FT3水平在青春发育晚期随年龄变化较大,在13岁时的水平显著高于11、12岁(P<0.0001),在13岁后逐渐下降(P<0.0001);而FT4的水平在11~15岁总体上受年龄影响较小,13~15岁的水平略高于11~12岁(P<0.0001)。结论青春期女性的甲状腺功能指标TSH、FT3、FT4水平均与成人存在较大的差异,受年龄、青春期发育程度的影响有所不同,有必要进一步完善年龄和青春发育时期特定甲状腺指标参考区间。

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the CAI Yi-zhou and HE Dan-dan contributed equally to this work staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.0012)and the 13-year-old group(P<0.0001);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.0001).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.0001).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.