Thyroid Hormone Supplementation Therapy for Differentiated Thyroid Cancer After Lobectomy: 5 Years of Follow-Up

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. 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. 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.

TSH suppression therapy has been used to decrease thyroid cancer recurrence. However, validation of effects through studies providing a high level of evidence has been lacking. This single-center, open-label, randomized controlled trial tested the hypothesis that disease-free survival (DFS) for papillary thyroid carcinoma (PTC) in patients without TSH suppression is not inferior to that in patients with TSH suppression. Participants were randomly assigned to receive postoperative TSH suppression therapy (group A) or not (group B). Before assignment, patients were stratified into groups with low- and high-risk PTC according to the AMES (age, metastasis, extension, size) risk-group classification. For patients assigned to group A, L-T(4) was administered to keep serum TSH levels below 0.01 μU/ml. TSH levels were adjusted to within normal ranges for patients assigned to group B. Recurrence was evaluated by neck ultrasonography and chest computed tomography. Eligible participants were recruited from 1996-2005, with 218 patients assigned to group A and 215 patients to group B. Analysis was performed on an intention-to-treat basis. DFS did not differ significantly between groups. The 95% confidence interval of the hazard ratio for recurrence was 0.85-1.27 according to Cox proportional hazard modeling, within the margin of 2.12 required to declare 10% noninferiority. DFS for patients without TSH suppression was not inferior by more than 10% to DFS for patients with TSH suppression. Thyroid-conserving surgery without TSH suppression should be considered for patients with low-risk PTC to avoid potential adverse effects of TSH suppression.

The influence of thyrotropin (thyroid-stimulating hormone [TSH]) suppressive therapy on bone mineral density (BMD) remains contentious. We have conducted a randomized controlled trial evaluating the effects of postoperative TSH suppressive therapy on disease-free survival for papillary thyroid carcinoma (PTC) since 1996, while prospectively verifying the effects of TSH suppression on BMD. Lumbar spine BMD as expressed by T-score was examined annually in female patients randomly assigned to receive TSH suppressive therapy (group A; n = 144) or no therapy (group B; n = 127). The mean TSH level was 0.07 ± 0.10 mU/L in group A and 3.14 ± 1.69 mU/L in group B. Group B did not show any significant decrease in T-score until 5 years postoperatively, whereas group A had a significant deterioration from 1 year postoperatively. Among group A patients, significant decreases in T-score within 1 year were seen in patients ≥ 50 years of age, but not in those <50 years of age. After 5 years of TSH suppression, 20 patients had T-scores below -2.0 and 100 patients did not. These former patients were significantly older and had lower preoperative BMD measurements than the latter. This prospective controlled trial suggests that TSH suppression after surgery for PTC has adverse effects on BMD in women ≥ 50 years of age. Copyright © 2011 Mosby, Inc. All rights reserved.