CHICAGO — An individually tailored approach to providing thyroid hormone replacement in thyroid cancer patients should be guided by the findings of several key studies, according to endocrinologist Giuseppe Barbesino.
The evidence at hand doesn't permit sweeping generalizations about what the target TSH level should be, said Dr. Barbesino of Harvard University, Boston.
He said his thinking was influenced by a study led by Dr. Jacqueline Jonklaas of Georgetown University, Washington. She and her colleagues analyzed a prospective multicenter registry and showed for the first time that it isn't necessary to drive TSH levels below 0.1 mU/L to improve overall survival in patients with stage II thyroid cancer. Survival can be improved in such patients with moderate TSH suppression in the range of 0.1 but less than 0.5 mU/L (Thyroid 2006;16:1229–42).
That's important because aggressive TSH suppression to less than 0.1 mU/L in patients with differentiated thyroid cancer carries several downsides. It is associated with an increased risk of new-onset atrial fibrillation, an increase in left ventricular mass index and other echocardiographic abnormalities, and some as-yet-inconclusive evidence suggesting increased risks of cardiovascular mortality, fracture, and decreased bone mineral density, Dr. Barbesino said at a satellite symposium held in conjunction with the annual meeting of the American Thyroid Association.
The abnormalities of cardiac structure and function associated with TSH suppression in thyroid cancer patients are subtle, and their clinical significance remains unclear. But researchers at the University of Cagliari (Italy) have shown that these abnormalities—including left ventricular posterior wall thickening, increased intraventricular septum thickness, increased left ventricular end-diastolic dimension, and an associated diminished exercise tolerance—are reversible by titrating the levothyroxine dose down to the minimum still capable of inducing TSH suppression (J. Clin. Endocrinol. Metab. 2000;85:159–64).
It remains an open question as to whether TSH suppression with levothyroxine reduces bone mineral density and increases fracture risk, Dr. Barbesino said at the symposium supported by Abbott Laboratories, maker of a test for TSH.
He suggested reserving aggressive TSH suppression to less than 0.1 mU/L for patients with high-risk stage III-IV or incurable tumors, since that approach has been shown to improve overall survival. Consider a target level of 0.1 to less than 0.5 mU/L in patients with low-risk tumors prior to restaging, and in patients with high-risk tumors who have had several years with no disease activity, particularly if the patients are over age 60, when the increased risk of atrial fibrillation associated with aggressive TSH suppression is likely to be most damaging.
Reserve mild TSH suppression to 0.5 to less than 2.5 mU/L for patients with microcarcinomas or tumors deemed low risk following negative restaging. Dr. Barbesino said he tries to avoid TSH levels of 2.5 mU/L or more in thyroid cancer patients. He is especially careful to keep levels under 5.0 mU/L because values above that are associated with rapid growth of metastases.
He disclosed having received honoraria from Genzyme Corp., maker of Thyrogen (thyrotropin alfa for injection).