Moderate TSH Suppression Best

Published: Oct 31, 2014 | Updated: Nov 3, 2014

By Kristina Fiore, Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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Study Author: Brian Haugen, MD 
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Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• In patients with differentiated thyroid cancer, total/near-total thyroidectomy with moderate TSH-suppressive thyroid hormone therapy was independently predictive of improved disease free survival.

SAN DIEGO -- Moderately suppressing thyroid-stimulating hormone (TSH) after treatment for differentiated thyroid cancer may be the best strategy, researchers reported here.

In an analysis of registry data, moderate TSH suppression was associated with better overall survival and disease-free survival -- but aggressive suppression was not, Aubrey Carhill, MD, of the University of Texas MD Anderson Cancer Center, reported during an oral session here at the American Thyroid Association meeting.

And moderate suppression was independently associated with overall survival when given for 1 or 3 years, but not 5 years, Carhill said.

"Aggressive TSH suppression confers no additional survival advantage compared with moderate TSH suppression," Carhill said during the presentation.

There's a dearth of prospective trials of initial treatments for patients with differentiated thyroid cancer, and thus there is considerable debate about the appropriate extent of TSH suppression following treatment, she explained, with much guidance based on expert consensus.

Currently, the ATA recommends TSH suppression following treatment for differentiated thyroid cancer by risk category. Those with persistent disease (<0.1 mU/L) should be suppressed indefinitely, while those who are disease-free but still high-risk (0.1 to 0.5 mU/L) should be suppressed for 5 to 10 years.

There is no specification for low-risk, disease-free patients (0.3 to 3 mU/L).

Carhill and colleagues analyzed data from the National Thyroid Cancer Treatment Cooperative Study Group, a multi-institutional registry running from 1987 to 2012 that prospectively collected data related to clinical outcomes following initial treatment of differentiated thyroid cancer.

They looked at the effects of initial therapies of thyroidectomy and radioiodine, along with long-term TSH suppression in 4,941 treated patients who had a median of 6 years of follow-up.

Overall survival was improved for stage III patients who received radioiodine therapy (RR 0.66, 95%CI 0.46 to 0.98, P=0.04), and there was a trend toward improved overall survival in stage IV patients who had either a thyroidectomy or radioiodine therapy (RR 0.66 and o.70, respectively, P=0.049 combined).

Carhill and colleagues reported that moderate -- but not aggressive -- TSH suppression was associated with significantly improved overall survival in all disease stages:

• Stage I: RR 0.10, 95% CI 0.02 to 0.60, P=0.01
• Stage II: RR 0.05, 95% CI 0.02 to 0.15, P<0.0001
• Stage III: RR 0.15, 95% CI 0.08 to 0.29, P<0.0001
• Stage IV: RR 0.30, 95% CI 0.14 to 0.73, P=0.01

Moderate suppression was also associated with improved disease-free survival:

• Stage I: RR 0.35, 95% CI 0.21 to 0.61, P=0.0004
• Stage II: RR 0.37, 95% CI 0.19 to 0.76, P=0.009
• Stage III: RR 0.19, 95% CI 0.11 to 0.34, P<0.0001

The advantages of moderate suppression also held for distant metastatic disease, the researchers said. Only moderate TSH suppression was associated with significantly improved overall survival when distant metastatic disease was diagnosed during follow-up (RR 0.34, 95% CI 0.19 to 0.65, P=0.0018).

And the length of time also mattered, the researchers said. Moderate suppression was independently associated with overall survival benefit if given for 1 year (RR 0.31, 95% CI 0.19 to 0.54) or 3 years (RR 0.29, 95% CI 0.15 to 0.60) -- but not if it is given for 5 years, Carhill reported.

She said the fact that only moderate suppression holds survival advantages is contrary to earlier reports and analyses from this database, some of which have shown that aggressive TSH suppression was associated with improved overall survival in high-risk patients.

Although the study was limited by the potential for institutional bias, since physicians could assign disease status at entry and could select the therapy, Carhill and colleagues still concluded that moderate TSH suppression is beneficial for at least 3 years after diagnosis.

"Aggressive TSH suppression may not be warranted even in patients diagnosed with distant metastatic disease during follow-up," she said. "Moderate TSH stimulation continued at least 3 years after diagnosis may be indicated in higher-risk patients."

Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center in New York, and chair of this year's scientific program committee, noted that thyroid cancer specialists "have been doing less intense therapy these days," given questions such as how-long and how-much when it comes to TSH suppression.

"We used to keep TSH suppressed forever," Tuttle told MedPage Today, "but we saw some complications, including osteoporosis and atrial fibrillation."

But this new study "helps us understand which patients need that suppression," he said, "and which patients you can do less to."