On the Relative Ineffectiveness of TSH- Normalizing T4 Therapy

In the treatment of primary hypothyroidism, guidelines issued by some organizations advise merely normalizing the TSH, reducing it to any value within the reference range. However, many studies show that this approach often produces little improvement in symptoms or in the risk of diseases associated with hypothyroidism. For this reason, some organizations and experts recommend titrating T4 doses to reduce the TSH to low values within the reference range. The data indicate that once-daily oral T4 therapy differs from endogenous thyroid hormone production in several ways that can cause the degree of TSH-lowering to be excessive relative to the thyroid hormone effects in most tissues. Lacking an objective test that can reliably assess thyroid hormone sufficiency in all tissues of the body with thyroid replacement, dosing must be guided not by a “normal” TSH but the free thyroid hormone levels, by physiological indicators of thyroid hormone effect, and ultimately by the patient’s subjective and objective clinical response.