Department of Medicine, Neurology, Halland County Hospital, Halmstad, Sweden.
School of Medical Sciences, Örebro University, Örebro, Sweden.
J Neuroendocrinol. 2023 May;35(5):e13272. doi: 10.1111/jne.13272. Epub 2023 Apr 22.
Up to 20% of individuals with primary hypothyroidism treated with L-thyroxine still suffer from severe symptoms. These are supposedly brain derived and involve both cognitive and emotional domains. Previously, no consistent relationship has been found between thyroid hormones (TH) or TSH levels in blood and quality of life (QoL). Recently, we reported an association between cerebrospinal fluid (CSF)/serum free-thyroxine (f-T4) ratio and QoL, in juvenile hypothyroid patients. Here, we investigated if CSF/serum f-T4 ratio and QoL estimates correlate also during L-thyroxine treatment. Moreover, the CSF biomarker neurogranin (Ng) was used as a biomarker for synaptic function and integrity in clinical research. Ng is partially controlled by TH and therefore we investigated the relationship between QoL parameters and Ng levels. Patients diagnosed with primary hypothyroidism were investigated using vital parameters, serum and CSF analyses of TH, TSH, Ng and QoL questionnaires. Similar procedures were performed after 6 months of treatment. The most marked associations with QoL were found for CSF/serum f-T4 ratio, which was strongly related to several QoL parameters such as the mental subscore of SF-36 (r = 0.83, p < .0005). Ng, which did not differ from that in our healthy controls, was lower in some patients during treatment and higher in others. However, the change in Ng during treatment was significantly correlated with QoL parameters including the mental subscore of SF-36 (r = -0.86, p < .0001). In addition, the CSF/serum f-T4 ratio correlated with the change in Ng (r = -0.75, p = .001). Our results suggest that the ratio between CSF and serum f-T4 is an important biomarker for QoL during treatment of patients with primary hypothyroidism, so far in research, but in the future maybe also in clinical settings. Moreover, this ratio also correlates with the changes in Ng levels during L-thyroxine treatment, further supporting the impact of the TH balance between serum and CSF on QoL.
高达 20%的原发性甲状腺功能减退症患者在接受 L-甲状腺素治疗后仍有严重症状。这些症状据称源自大脑，涉及认知和情绪领域。此前，人们并未发现血液中的甲状腺激素 (TH) 或 TSH 水平与生活质量 (QoL) 之间存在一致关系。最近，我们报告了在青少年甲状腺功能减退症患者中，脑脊液 (CSF)/血清游离甲状腺素 (f-T4) 比值与 QoL 之间的关联。在这里，我们研究了在 L-甲状腺素治疗期间，CSF/血清 f-T4 比值和 QoL 估计值是否也相关。此外，神经颗粒蛋白 (Ng) 作为临床研究中突触功能和完整性的生物标志物。Ng 部分受 TH 控制，因此我们研究了 QoL 参数与 Ng 水平之间的关系。通过生命参数、TH、TSH、Ng 和 QoL 问卷的血清和 CSF 分析，对诊断为原发性甲状腺功能减退症的患者进行了研究。在治疗 6 个月后进行了类似的程序。与 QoL 最显著相关的是 CSF/血清 f-T4 比值，该比值与 SF-36 的心理子评分等多个 QoL 参数密切相关（r=0.83，p<0.0005）。Ng 与我们的健康对照组没有差异，但在一些患者中在治疗期间较低，而在另一些患者中较高。然而，治疗期间 Ng 的变化与包括 SF-36 的心理子评分在内的 QoL 参数显著相关（r=-0.86，p<0.0001）。此外，CSF/血清 f-T4 比值与 Ng 的变化相关（r=-0.75，p=0.001）。我们的研究结果表明，CSF 与血清 f-T4 的比值是原发性甲状腺功能减退症患者治疗期间 QoL 的重要生物标志物，迄今为止，该比值仅在研究中得到了证实，但在未来，它可能也会在临床环境中得到应用。此外，该比值还与 L-甲状腺素治疗期间 Ng 水平的变化相关，进一步支持了血清和 CSF 之间 TH 平衡对 QoL 的影响。
