Chaker Layal, Korevaar Tim I M, Medici Marco, Uitterlinden André G, Hofman Albert, Dehghan Abbas, Franco Oscar H, Peeters Robin P
1 Rotterdam Thyroid Center, Erasmus University Medical Center , Rotterdam, The Netherlands .
2 Department of Internal Medicine, Erasmus University Medical Center , Rotterdam, The Netherlands .
Thyroid. 2016 Sep;26(9):1195-204. doi: 10.1089/thy.2016.0133.
Information on determinants and change of thyroid function over time is sparse and conflicting but crucial for clinical interpretation and research. Therefore, our aim was to systematically investigate determinants of thyroid-stimulating hormone (TSH), free thyroxine (FT4) (as markers of thyroid function), their mutual relation (as marker of thyroid function set point) and changes in thyroid function over time.
We included 9402 participants from the Rotterdam Study not taking thyroid medication and with available thyroid function measurements. Repeated measurements (6.5-year interval) were available for 1225 participants. The association of selected determinants with TSH, FT4, and their mutual relation (reflecting thyroid function set point) was estimated using linear regression models using restricted cubic splines with three knots. The factors investigated were age, sex, body mass index (BMI), tobacco smoking, alcohol use, thyroperoxidase antibodies (TPOAb), and common genetic factors.
Most influential determinants of TSH were age, smoking, genetic determinants, and TPOAb levels (p < 0.001). For FT4, most influential determinants were age, BMI, sex, genetic determinants and TPOAb levels (p < 0.001). Older age, female sex, and increased TPOAb levels were associated with a stronger relation between TSH and FT4. TSH levels did not change over time, irrespective of age. FT4 levels increased over time, most prominently in those older than 65 years of age (mean increase of 4.5 pmol/L).
The main factors that influence the relationship between thyroid hormone and molar concentrations of TSH in our population-based cohort study are age, smoking, BMI, TPOAb levels, and common genetic variants. The set point that determines TSH secretion as it relates to negative thyroid hormone feedback is modified by age, sex and TPOAb positivity. FT4 levels increase over time, with a more pronounced increase in the elderly, while TSH values seem stable over time. Our results question the current notion of an increase of TSH with increasing age.
关于甲状腺功能的决定因素及其随时间变化的信息稀少且相互矛盾，但对于临床解读和研究至关重要。因此，我们的目的是系统地研究促甲状腺激素（TSH）、游离甲状腺素（FT4）（作为甲状腺功能的标志物）的决定因素、它们之间的相互关系（作为甲状腺功能设定点的标志物）以及甲状腺功能随时间的变化。
我们纳入了鹿特丹研究中9402名未服用甲状腺药物且有可用甲状腺功能测量值的参与者。1225名参与者有重复测量值（间隔6.5年）。使用具有三个节点的受限立方样条的线性回归模型估计所选决定因素与TSH、FT4及其相互关系（反映甲状腺功能设定点）之间的关联。研究的因素包括年龄、性别、体重指数（BMI）、吸烟、饮酒、甲状腺过氧化物酶抗体（TPOAb）和常见遗传因素。
TSH最有影响力的决定因素是年龄、吸烟、遗传决定因素和TPOAb水平（p < 0.001）。对于FT4，最有影响力的决定因素是年龄、BMI、性别、遗传决定因素和TPOAb水平（p < 0.001）。年龄较大、女性以及TPOAb水平升高与TSH和FT4之间更强的关系相关。无论年龄如何，TSH水平随时间没有变化。FT4水平随时间升高，在65岁以上人群中最为显著（平均升高4.5 pmol/L）。
在我们基于人群的队列研究中，影响甲状腺激素与TSH摩尔浓度之间关系的主要因素是年龄、吸烟、BMI、TPOAb水平和常见基因变异。与甲状腺激素负反馈相关的决定TSH分泌的设定点会因年龄、性别和TPOAb阳性而改变。FT4水平随时间升高，老年人升高更为明显，而TSH值随时间似乎稳定。我们的结果对目前认为TSH随年龄增加而升高的观点提出了质疑。
