Endocrine Abstracts

Background: Despite receiving biochemically adequate levothyroxine replacement, many patients with primary hypothyroidism suffer from persistent symptoms and a reduced quality of life (QoL). The underlying causes of this phenomenon are not fully understood, but psychological factors, autoimmune inflammation, and variations in thyroxine conversion have all been suggested as potential contributors. At this time, however, there is no consensus on the root cause.

Methods: In this cross-sectional study we aimed to explore the potential impact of various demographic, anamnestic, psychometric, and laboratory predictors on disease-specific quality of life, as measured by the Thyroid-Dependent Quality of Life questionnaire. To minimize confounding factors, we applied stringent inclusion criteria including a disease duration of at least two years, a stable thyroxine dose and normal TSH level for at least six months, and no significant medical or psychological comorbidities. The assessed psychometric covariates were somatization (Somatosensory Amplification Scale), depression (Patient Health Questionnaire-9), and symptom number (Underactive Thyroid Symptom Rating Questionnaire). Determinants of QoL were assessed using uni- and multivariate linear modeling with robust corrections, as well as mediation analysis.

Results: Our final study sample consisted of 157 patients, of whom 70.7% had Hashimoto’s thyroiditis and 29.3% had hypothyroidism of iatrogenic origin (eg. cancer, thyroidectomy, or post-radioiodine treatment). The mean age of participants was 49.5 ± 14.5 years, average disease duration 11.2 ± 8.2 years, thyroxine dose 1.2 ± 0.4 mg/kg body weight, and a TSH level 1.8 ± 0.9 mIU/l. We found no significant association between QoL and thyroid-specific laboratory parameters, including TSH, FT3, FT4, rT3, anti-TPO, and SHBG. Using a multivariate model we identified somatization (B=-0.59, P=0.005), BMI (B=-0.08, P=0.015), and symptom number (B=-0.11, P=0.043) as the primary determinants of quality of life (r² = 0.34). Mediation analysis also revealed a significant indirect effect of depression on QoL, mediated primarily by somatization and BMI. In this later model 49% of the variation in symptom number was related to depression and somatization. After adjusting for psychometric factors, etiology had no effect in either analysis.

Conclusions: Our study suggests that psychological factors play a paramount role in determining quality of life of hypothyroid individuals receiving adequate levothyroxine replacement. Our findings do not support the notion that autoimmune inflammation or tissue-level hypothyroidism has a significant influence on QoL.