Persistent Hypothyroid Symptoms Despite Adequate Thyroid Hormone Replacement

The majority of patients with hypothyroidism who are treated with thyroid hormone replacement to maintain serum TSH levels within the population reference range experience complete resolution of their hypothyroid symptoms. However, a significant minority have persistent symptoms and express dissatisfaction with their treatment. These patients usually benefit from seeing attentive and compassionate providers who listen carefully to their concerns and work with them to explore solutions. They should be evaluated for other coexistent autoimmune and systemic disorders and be encouraged to engage in healthy lifestyle practices. It is often productive to carefully explain that nonspecific symptoms are common in the population and are often not related to thyroid disease. A polymorphism (Thr92Ala) of the deiodinase 2 enzyme, which converts thyroxine (T4) to triiodothyronine (T3) in the brain, is present in approximately 16% of the population. These patients have been reported in one study to respond better to combination therapy with levothyroxine (LT4) and liothyronine (LT3); however genetic testing for this polymorphism is expensive and not recommended. Current clinical practice guidelines stress that replacement with LT4 is the treatment of choice for patients with hypothyroidism; however, a trial of combination LT4 and LT3 or of desiccated thyroid extract with maintenance of serum TSH levels within the reference range is considered reasonable to determine if these patients may experience better symptom relief than they have had with LT4 monotherapy.