What is the role of thyroid suppression therapy in patients with a history of thyroid cancer?

From the Guidelines

Thyroid suppression therapy is recommended for patients with a history of thyroid cancer to reduce the risk of recurrence, with the goal of maintaining serum TSH levels below 0.1 mIU/L for high-risk patients and within the normal range for low-risk patients. The standard approach involves administering levothyroxine (T4) at doses sufficient to suppress thyroid-stimulating hormone (TSH) below normal range 1. For high-risk patients with aggressive tumors or metastatic disease, TSH should be suppressed to below 0.1 mIU/L, as this has been shown to decrease progression and recurrence rates, and cancer-related mortality 1. In contrast, low-risk patients may maintain TSH at the lower end of normal range (0.5-2.0 mIU/L), as no significant improvement has been obtained by suppressing TSH in these patients 1.

Key Considerations

• Typical starting doses of levothyroxine range from 1.6-2.1 mcg/kg/day, with adjustments made based on TSH levels measured every 6-8 weeks until stable, then every 6-12 months 1.
• Side effects to monitor include cardiac issues (palpitations, atrial fibrillation), bone loss, and symptoms of hyperthyroidism 1.
• The duration of suppression therapy depends on recurrence risk and response to treatment, with lifelong therapy often needed for high-risk patients, while low-risk patients with no evidence of disease may eventually transition to normal TSH targets 1.
• Patients whose TSH levels are chronically suppressed should be counseled to ensure adequate daily intake of calcium (1200 mg/d) and vitamin D (1000 units/d) to mitigate the risk of bone demineralization 1.

From the FDA Drug Label

Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer The FDA drug label indicates that levothyroxine sodium can be used for thyroid suppression therapy in patients with a history of thyroid cancer, specifically for thyrotropin-dependent well-differentiated thyroid cancer as an adjunct to surgery and radioiodine therapy 2.

• The goal of therapy is to suppress TSH levels.
• Dosing must be individualized based on patient factors, including age, weight, and cardiovascular status.
• Monitoring of TSH and/or T4 levels, as well as clinical status, is necessary to determine the adequacy of therapy 2.

From the Research

Thyroid Suppression Therapy in Patients with a History of Thyroid Cancer

• The goal of thyroid suppression therapy is to lower serum thyrotropin (TSH) levels using doses of thyroid hormone in excess of what would normally be required to maintain a euthyroid state 3.
• TSH suppression is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer 4.
• However, aggressive TSH-suppressive therapy is of little or no benefit to the vast majority of patients with differentiated thyroid cancer (DTC) 5.
• The American Thyroid Association recommends a graded approach to TSH suppression, based on initial risk and ongoing risk assessment 3.

Benefits and Risks of TSH Suppression Therapy

• TSH suppression therapy can decrease progression and recurrence rates, and cancer-related mortality in high-risk thyroid cancer patients 6.
• However, TSH suppression implies a state of subclinical thyrotoxicosis, and can have negative outcomes such as osteoporosis, fracture, and cardiovascular disease 3.
• A study found that only 29.2% of DTC patients had serum TSH levels at target levels, while the remaining patients had TSH levels under or over the treatment range, exposing them to medication side effects 7.

Patient Compliance and TSH Suppression Therapy

• Patient compliance is crucial in achieving target TSH levels, and non-compliant patients may require higher doses of levothyroxine (LT4) 7.
• A study found that 50.1% of patients were good compliant, 32.7% were moderate compliant, and 17.1% were non-compliant with LT4 therapy 7.
• Reaching TSH targets requires simplified and applicable guidelines, and following guideline recommendations 7.

Ongoing Research and Future Directions

• A multicenter, randomized, controlled trial is currently underway to assess the usefulness of suppressing TSH target levels after thyroid lobectomy in low to intermediate risk thyroid cancer patients 4.
• The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients 4.
• Large randomized controlled studies are needed to confirm the presumed oncological benefits of TSH-suppression and its causal role in adverse cardiac, skeletal, and quality of life effects 5.