Objective: To determine whether subclinical thyrotoxicosis alters health status, mood, and/or cognitive function.

Design: Double-blinded, randomized, cross-over study of usual dose L-thyroxine (L-T4) (euthyroid arm) vs. higher dose L-T4 (subclinical thyrotoxicosis arm) in hypothyroid subjects.

Patients: Thirty-three hypothyroid subjects receiving L-T4.

Measurements: Subjects underwent measurements of health status, mood, and cognition: Short Form 36 (SF-36), Profile of Mood States (POMS), and tests of declarative memory (Paragraph Recall, Complex Figure), working memory (N-Back, Subject Ordered Pointing, Digit Span Backwards), and motor learning (Pursuit Rotor). These were repeated after 12 weeks on each of the study arms.

Results: Mean TSH levels decreased from 2.15 to 0.17 mU/L on the subclinical thyrotoxicosis arm (p<.0001), with normal mean free T4 and free T3 levels. The SF-36 physical component summary (PCS) and general health (GH) subscale were slightly worse during the subclinical thyrotoxicosis arm, while the mental health subscale was marginally improved. The POMS confusion, depression, and tension subscales were improved during the subclinical thyrotoxicosis arm. Motor learning was better during the subclinical thyrotoxicosis arm, while declarative and working memory measures did not change. This improvement was related to changes in the SF-36 PCS and POMS tension subscales and free T3 levels.

Conclusions: We found slightly impaired physical health status, but improvements in measures of mental health and mood in L-T4 treated hypothyroid subjects when subclinical thyrotoxocosis was induced in a blinded, randomized fashion. Motor learning was also improved. These findings suggest that thyroid hormone directly affects brain areas responsible for affect and motor function.