Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial.

CONTEXT: In patients with primary hypothyroidism, anecdotal evidence suggests that well-being is optimized by fine adjustment of T(4) dosage, aiming for a serum TSH concentration in the lower reference range. This has not been tested in a clinical trial.

OBJECTIVE: Our objective was to test whether adjustment of T(4) dosage aiming for a serum TSH concentration less than 2 mU/liter improves well-being compared with a serum TSH concentration in the upper reference range.

DESIGN: We conducted a double-blind, randomized clinical trial with a crossover design.

PARTICIPANTS: Fifty-six subjects (52 females) with primary hypothyroidism taking T(4) (>/=100 microg/d) with baseline serum TSH 0.1-4.8 mU/liter participated.

INTERVENTIONS: Each subject received three T(4) doses (low, middle, and high in 25-microg increments) in random order.

OUTCOME MEASURES: Outcome measures included visual analog scales assessing well-being (the primary endpoint) and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference.

RESULTS: Mean (+/- sem) serum TSH concentrations were 2.8 +/- 0.4, 1.0 +/- 0.2, and 0.3 +/- 0.1 mU/liter for the three treatments. There were no significant treatment effects on any of the instruments assessing well-being, symptoms, quality of life, or cognitive function and no significant treatment preference.

CONCLUSIONS: Small changes in T(4) dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action. These data do not support the suggestion that the target TSH range for the treatment of primary hypothyroidism should differ from the general laboratory range.