Abstract
BACKGROUND: A significant number of patients with primary hypothyroidism report persistent symptoms and decreased quality of life (QoL) despite biochemically adequate levothyroxine replacement. Individual variations in thyroxine conversion, autoimmune inflammation, and psychological factors have all been implicated as a potential cause. METHODS: In this cross-sectional study we have examined the association of numerous demographic, disease-specific, and laboratory parameters as well as three patient reported outcome measures with thyroid-dependent QoL as measured by the Underactive Thyroid-Dependent Quality of Life Questionnaire. Patients were stringently selected to minimize the confounding effect of comorbidities or inadequate hormone replacement. We used validated questionnaires to assess somatosensory amplification, depression, and symptom number. Determinants of QoL were evaluated using uni- and multivariable linear modeling, and mediation analysis. RESULTS: Our final sample consisted of 157 patients. 70.7% had Hashimoto's, whereas 29.3% had iatrogenic hypothyroidism. Mean age was 49.5 ± 14.5 years, disease duration: 11.2 ± 8.2 years, thyroxine dose: 1.2 ug/kg bodyweight, TSH: 1.8 ± 0.9 mIU/L. Thyroid-specific biomarkers including TSH, FT3, FT4, rT3, SPINA-GD, anti-TPO, and SHBG had no association with thyroid-dependent QoL. Somatosensory amplification was a strong predictor of the presence and perceived bother of the most common hypothyroidism-associated symptoms. In our final multivariable model (r(2) = 0.31) the factors associated with thyroid-dependent QoL were somatosensory amplification (p = 0.002), BMI (p = 0.021), and depression (p < 0.001). CONCLUSION: These results suggest that psychological factors, particularly somatosensory amplification, might play a major role in influencing QoL in hypothyroid individuals on adequate levothyroxine replacement. Our findings do not corroborate a significant role for autoimmune inflammation or tissue-level hypothyroidism.