Better Outcomes Associated with Moderate Suppression of Thyroid-Stimulating Hormone

Only moderate suppression of thyroid-stimulating hormone (TSH) after initial therapy appears to be associated with better outcomes in all stages of differentiated thyroid cancer (DTC), including low-risk stage I disease, according to new data presented at the 84th Annual Meeting of the American Thyroid Association.

The National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG) conducted an analysis of 4,941 patients treated with standard initial therapies for differentiated thyroid cancer. An updated analysis presented at this meeting showed aggressive TSH-suppressive thyroid hormone therapy (THST) does not appear to be warranted, even in those patients diagnosed with distant metastatic disease during follow-up.

Moderate THST was defined as TSH maintained at the subnormal-to-normal range and aggressive THST was defined as TSH maintained at the undetectable-to-subnormal range.

“With our larger and more mature database, findings support earlier NTCTCSG registry findings.² We confirm that there is survival benefit in high-risk groups treated with total/near-total thyroidectomy and radioactive iodine, and no disease-free survival benefit in low-risk groups receiving radioactive iodine,” said Aubrey Carhill, MD, who is an assistant professor in the Department of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center in Houston.

There is no overwhelming consensus on the optimal regimens of surgery, postoperative radioiodine (RAI) and THST in patients with varying stages of DTC. To learn more, Dr. Carhill and her colleagues analyzed overall survival (OS) and disease-free survival (DFS) in patients after who underwent initial therapy for DTC (thyroidectomy, RAI) and long-term THST.

The patients have now been followed for a median of 6 years (34,631 person-years of documented follow-up time), and the data confirm previous findings that total/near-total thyroidectomy (T/NTT) followed by RAI is associated with a significant survival benefit in high-risk, but not low-risk, patients.

For this investigation, the researchers used the NTCTCSG staging system and determined OS and DFS by univariate and multivariate analyses. They found that there was an improvement in OS in stage III patients who received RAI (risk ratio [RR]=0.66; P=.04). In stage IV patients, they found there was also a significant improvement for those patients who received both T/NTT and RAI (RR=0.66 and 0.70; combined P=.049).

The investigators found that moderate but not aggressive THST was associated with significantly improved OS in all stages of disease. RRs were 0.13 in stage I disease, 0.09 in stage II disease, 0.13 in stage III disease and 0.33 in stage IV disease.

Moderate THST was also associated with improved DFS in stage I (RR=0.5), stage II (RR=0.40), and stage III (RR=0.18) disease. The researchers found that only moderate THST was associated with significantly improved OS when distant metastatic disease occurred at long-term follow-up.

“We report for the first time, in multivariate analysis of primary treatments for DTC, only moderate THST was associated with both improved OS and DFS. Further, when examining the degree of THST, aggressive THST conferred no additional survival advantage as compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease. This has tremendous implications given the known risks associated with long-term thyrotoxicosis,” Dr. Carhill told Endocrinology Advisor.

“Lastly, we found when evaluating the optimal duration of THST, and examining the effect of continuing degrees of suppression beyond 1, 3 and 5 years of follow-up, continued moderate THST is beneficial for at least 3 years following diagnosis.”