Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism – A pilot study: CSF/s-T4 associated with QoL in hypothyroidism

Research output: Contribution to journalArticle


Background & Objective: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). Methods: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. Results: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. Conclusions: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.


External organisations
  • Halmstad County Hospital
  • Karolinska University Hospital
  • Sahlgrenska Academy
  • Västmanland Hospital
  • Örebro University Hospital
  • Karolinska Institutet
  • Örebro University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • MADRS, Mild hypothyroidism, Quality of life, Subclinical hypothyroidism, Thyroxine, Triiodothyronine
Original languageEnglish
Article number100218
JournalJournal of Clinical and Translational Endocrinology
Publication statusPublished - 2020 Mar 1
Publication categoryResearch