Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement

Endocrine. 2018 Oct;62(1):136-143. doi: 10.1007/s12020-018-1649-6. Epub 2018 Jun 29.


Objective: Intrinsic imperfections of thyroid hormone replacement therapy may affect long-term general well-being. In patients with Hashimoto thyroiditis (HT), cognitive functioning may be affected via altered thyroid hormones action as well as by the autoimmune process. The aim of this study was to evaluate cognitive function and quality of life (QoL) in patients on long-term levothyroxine replacement for HT in relation to thyroid function tests and TPO (thyroid-peroxidase) antibody (TPOAb) status.

Design: Retrospective cross-sectional study.

Patients and measurements: One-hundred-and thirty patients with HT on long-term levothyroxine replacement and 111 euthyroid control subjects. Both groups were divided into two age subgroups, 20-49 years (N = 59 vs N = 79) and > 50 years (N = 71 vs N = 32). Evaluation included biochemical and neuropsychological tests, evaluating attention, global cognitive status, verbal and working memory, executive function, depression and anxiety, and quality of life. We used ANOVA and partial correlations to test for significant associations.

Results: FT4 (free-thyroxine), FT3 (free-triiodothyronine) levels and FT3/FT4 ratio were not different between patients and controls. Mean TSH (thyroid-stimulating hormone) was normal in all subjects but significantly higher in the patients (20-49 yrs:3.64 ± 2.74 vs 1.93 ± 1.10, >50 yrs:3.93 ± 2.84 vs 1.91 ± 0.90). Antibodies (TgAb,TPOAb) were higher in patients. Global cognitive function (MMSE-Mini mental state examination), conceptual tracking (TMT-Trail Making Test:A/B), verbal divergent thinking (like Phonemic fluency test), and anxiety and depression scores were significantly worse in patients vs controls. QoL was impaired in patients. there was a significant negative correlation between antibodies (TPOAb, TgAb) and quality in life (total SF36 score).

Conclusion: Patients on long-term levothyroxine replacement show persistent impairments in both cognitive functioning and general well-being.

Keywords: Anti-TPO; Cognitive function; Hypothyroidism; L-thyroxine; Long-term replacement; Quality of life.

MeSH terms

  • Adult
  • Attention / physiology
  • Cognition / physiology*
  • Cross-Sectional Studies
  • Executive Function / physiology
  • Female
  • Hashimoto Disease / drug therapy
  • Hashimoto Disease / psychology*
  • Hormone Replacement Therapy / psychology*
  • Humans
  • Male
  • Memory, Short-Term / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Quality of Life / psychology*
  • Retrospective Studies
  • Thyroxine / therapeutic use*
  • Young Adult


  • Thyroxine