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. 2025 May 26;25(1):136.
doi: 10.1186/s12902-025-01962-9.

Psychological factors and obesity, not thyroid biomarkers, predict thyroid-dependent quality of life in treated hypothyroidism: a cross-sectional study

Bence Bakos  1 , Tibor Solymosi  2 , Balázs Szili  2 , Ágnes Vincze  3 , Szilvia Mészáros  2 , Márk Stempler  2 , Richárd Ármós  2 , András Kiss  2 , Anna Bakos  4 , Nikolette Szücs  2 , Péter Reismann  2 , Judit Tőke  2 , Péter Pusztai  3 , Péter Lakatos  2 , István Takács  2
Affiliations

Psychological factors and obesity, not thyroid biomarkers, predict thyroid-dependent quality of life in treated hypothyroidism: a cross-sectional study

Bence Bakos et al. BMC Endocr Disord. .

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 (r2 = 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.

Keywords: Depression; Hypothyroidism; Obesity; Quality of life; Reverse-T3; Somatosensory amplification.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the National Scientific and Ethical Committee of the Hungarian Medical Research Council (No.: 38233–1/2019/EKU) and was conducted in accordance with the World Medical Association’s Declaration of Helsinki. Written informed consent was obtained from all participants before entering and prior to all study-related procedures. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Distribution of AWI-14 scores in our sample, with exponential curve shown. Visual inspection of the histogram, but not the K-S test (p < 0.001), suggested an exponential distribution
Fig. 2
Fig. 2
Mediation models exploring potential pathways between variables that showed a significant multivariable association with AWI-14. Model a. considers both depression (PHQ-9) and somatosensory amplification (SSAS) to be antecedent to AWI-14. Model b. considers somatosensory amplification to be antecedent and depression to be consequent to AWI-14. Standardized effect sizes are presented, non-significant pathways are omitted for clarity. ** p < 0.01
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