Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer

Background: Despite clinical practice guidelines for the management of differentiated thyroid cancer (DTC), there are no recommendations on the optimal serum thyrotropin (TSH) concentration to reduce tumor recurrences and improve survival, while ensuring an optimal quality of life with minimal adverse effects. The aim of this review was to provide a risk-adapted management scheme for levothyroxine (L-T4) therapy in patients with DTC. The objective was to establish which patients require complete suppression of serum TSH levels, given their risk of recurrent or metastatic DTC, and how potential adverse effects on the heart and skeleton, induced by subclinical hyperthyroidism, in concert with advanced age and comorbidities, may influence the degree of TSH suppression. Summary: A risk-stratified approach to predict the rate of recurrence and death from thyroid cancer was based on the recently revised American Thyroid Association guidelines. A stratified approach to predict the risk from the adverse effects of L-T4 was devised, taking into account the age of the patient, as well as the presence of preexisting cardiovascular and skeletal risk factors that might predispose to the development of long-term adverse cardiovascular or skeletal outcomes, particularly increased heart rate and left ventricular mass, atrial fibrillation, and osteoporosis. Nine potential patient categories can be defined, with differing TSH targets for both initial and long-term L-T4 therapy. Conclusion: Before deciding on the degree of TSH suppression during initial and long-term L-T4 treatment in patients with DTC, it is necessary to consider the aggressiveness of DTC, as well as the potential for adverse effects induced by iatrogenic subclinical hyperthyroidism. More aggressive TSH suppression is indicated in patients with high-risk disease or recurrent tumor, whereas less aggressive TSH suppression is reasonable in low-risk patients. In patients with high-risk DTC and an equally high risk of adverse effects, long-term treatment with L-T4 therapy should be individualized and balanced against the potential for adverse effects. In patients with an intermediate risk for thyroid cancer recurrence and a high risk of adverse effects of therapy, the degree of TSH suppression should be reevaluated during the follow-up period. Normalization of serum TSH is advisable for long-term treatment of disease-free elderly patients with DTC and significant comorbidities.