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Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine

Funkquist, A; Wandt, B; Blennow, K; Zetterberg, H; Svensson, J; Bjellerup, P; Freund-Levi, Y; (2023) Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine. Journal of Neuroendocrinology , Article e13272. 10.1111/jne.13272. (In press). Green open access

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Abstract

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.

Type: Article
Title: Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/jne.13272
Publisher version: https://doi.org/10.1111/jne.13272
Language: English
Additional information: © 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Cerebrospinal fluid biomarkers, cognition, neurogranin, primary hypothyroidism, quality of life
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10169325
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