Background: Hypothyroidism is a common endocrine disorder and the standard treatment is replacement therapy with levothyroxine (LT4). Although many hypothyroid patients improve upon treatment with LT4, a proportion seems to experience residual hypothyroid complaints despite treatment, even when plasma TSH and FT4 are within reference ranges.

Methods: Using an on-line survey we investigated 1. the health-related quality of life (QoL) (ThyPRO), 2. the activities of daily living (SF-36), 3. hypothyroid-related symptoms (ThySHI) in diagnosed, treated hypothyroid patients (>18 years, treated >6 months) and control persons (without thyroid disease, >18 years). In patients, the time course of symptoms from diagnosis until 3 years was asked (retrospectively, ThySHI). Patients and control persons were recruited by e-mails from patient organizations, posters in pharmacies and health centers and Twitter/Facebook. For data analysis (ThyPRO, 0-100 scale, t-test; daily functioning, 1-5 scale and ThySHI 0-3 scale, Mann-Whitney; time course symptoms, Friedmann-Dunnett; confounding factors, ANCOVA) IBM SPSS 24 was used.

Results: In this cohort consisted of 1667 patients (mean duration of illness 12.2 ± SD 9.9 years) and 275 controls. Treated hypothyroid patients had 1. a significant decrease in health-related QoL and all domains (fatigue, vitality, cognition, anxiety, depressivity, emotional susceptibility, social life, daily life), as compared to controls (mean total QoL 39.9 vs 19.1 resp. and all domains p<0.001), 2. Significantly more impairment with activities of daily living (p<0.001), and 3. significantly higher scores for symptoms related to hypothyroidism, as compared to control persons (all p<0.01). Symptoms generally decreased after 3 years of treatment, with fatigue, reduce daily functioning, coldness, muscle pain/cramps and being overweight as the most intense residual complaints. Many patients (78.5%) reported having complaints despite taking thyroid medication and reported not feeling well (77.8%) while their blood values were within range. TSH level, age, gender and duration of illness did not significantly affect total QoL, whereas the M3 comorbidity index did. Desiccated thyroid hormone users (9.4%) had a significantly better mean total QoL than LT4 users (90.5%) (36,0 vs 40.6, p=0.003).

Conclusions: Persistent complaints, such as reduced health-related quality of life, reduced daily functioning, and residual hypothyroid related symptoms, are common in this group of hypothyroid patients despite replacement therapy. Caregivers should be aware that persistent complaints can be present in treated hypothyroid patients, despite following current guidelines, and that these remaining symptoms may affect their quality of life and daily functioning.