Therapeutic challenges in the application of serum thyroid stimulating hormone testing in the management of patients with hypothyroidism on replacement thyroid hormone therapy: a review

Normalizing serum thyroid stimulating hormone (TSH) levels by lifelong treatment with levothyroxine (LT4) remains the primary goal of therapy for patients with hypothyroidism. The reference ranges for TSH are derived from populations with (supposedly) normal thyroid function. But, TSH results are affected by a number of factors including alterations in TSH levels with age, concurrent illnesses, circadian rhythm, inter- and intra-assay differences, and some commonly used medications that interfere with thyroid function or the TSH test. Furthermore, some patients are complex to manage and bringing serum TSH to within its reference range does not always resolve their symptoms of hypothyroidism. Furthermore, changes in TSH within the reference range may provoke symptoms in some sensitive patients, and others may have a personal set point for thyroid hormone levels that represents normal function for that individual, but which is outside the population reference range. The introduction of updated LT4 formulations, with better dosing accuracy and stability compared with older versions, should, in theory at least, provide better stability and accuracy of dosing over time. However, the new LT4 formulations are associated with manifold increases in the number of self-reported adverse events. Therefore, patients with hypothyroidism as well as the clinicians managing them need to better understand the utility as well as the limitations of the widely used TSH measurement. In addition, both pharmaceutical companies and the prescribing clinician need to take greater care when patients are switched from older to newer formulations.