Critical Approach to Hypothyroid Patients With Persistent Symptoms

Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms. Some population-based studies and international population-based surveys have confirmed dissatisfaction with LT4 treatment in some hypothyroid patients. It is well established that hypothyroid patients treated with LT4 exhibit higher serum thyroxine:triiodothyronine ratios and can have a persistent increase in cardiovascular risk factors. Moreover, variants in deiodinases and thyroid hormone transporter genes have been associated with subnormal T3 concentrations, persistent symptoms in LT4-treated patients, and improvement in response to the addition of liothyronine to LT4 therapy. The American (ATA) and European Thyroid Association (ETA) guidelines have recently evolved in their recognition of the potential limitations of LT4. This shift is reflected in prescribing patterns: Physicians' use of combination therapy is prevalent and possibly increasing. Randomized clinical trials have recently been published and, while they have found no improvement in treating hypothyroid patients, a number of important limitations did not allow generalizability. Meta-analyses have reported a preference rate for combination therapy in 46.2% hypothyroid patients treated with LT4. To promote discussions about an optimal study design, the ATA, ETA, and British Thyroid Association have recently published a consensus document. Our study provides a useful counterpoint on the controversial benefits of treating hypothyroid patients with combination therapy.