Context and Objective: An association between mood disorders and overt thyroid dysfunction is well established but there is little data on the potential for thyroid hormone levels closer to the "reference range" to correlate with psychological well-being.

Design, Setting and Patients: We analyzed the relationship between psychological wellbeing and free thyroxine (fT4), free triiodothyronine (fT3), TSH (TSH) and total reverse triiodothyronine (rT3) in 697 patients on thyroid hormone replacement therapy at entry to a randomized controlled trial of combined T4 and T3 replacement therapy. All patients were on 100 µg of thyroxine or more.

Interventions and Main outcome measures: Psychological well being was assessed with General Health Questionnaire-12 (GHQ-12), thyroid symptom questionnaire (TSQ) and Hospital Anxiety and Depression Scale (HADS).

Results: Free T4 and TSH showed a strong correlation with GHQ-12 scores (fT4 - b: -0.16, P = 0.005; TSH - b: 0.663, P = 0.04). No correlations were seen between the GHQ scores and free T3 (b:0.318, P = 0.275), rT3 (b:0.095, P = 0.95), rT3/fT4 ratio (b:71.83, P = 0.09) or fT3/rT3 ratio (b:0.05, P = 0.32). The correlations remained when the dataset was limited to patients with TSH in the range 0.3-4.0 mIU/L. Similar correlations were seen with the TSQ though not with the HADS scores.

Conclusions: Differences in free T4 and TSH concentration, even within the reference range, may be a determinant of psychological well-being in treated hypothyroid patients though not necessarily with symptoms typical of anxiety or depression.