According to experts, 10 to 20% of hypothyroid individuals fail to respond completely to T4-only (levothyroxine, Synthroid) treatment. Dr. Anthony Bianco, the president of the American Thyroid Association, and his associates believe this is due to genetic variations in the way thyroid hormone is converted in the body from T4 into T3. T3 is the much more potent form of thyroid hormone and unless the cells of the body receive enough T3, normal function cannot be achieved and symptoms of low thyroid such as fatigue, mental fogginess, constipation, muscle aches etc, persist. Based on the research conducted by Dr. Bianco and colleagues it is thought that in those with the genetic trait making T4 treatment ineffective, blood tests would show low T3 levels.
My colleagues, Dr. Paul Cassanova and Dr. Kathryn Reynolds and I at Palm Beach Diabetes and Endocrine Specialists researched this possibility. Our findings were presented at the recently concluded International Thyroid Congress held in Orlando, Florida. We looked back at the blood tests of our patients who continued to complain of hypothyroid symptoms despite receiving full doses of levothyroxine and who reported feeling much better after switching to combination T4 plus T3 therapy in the form of DTE. We were expecting to find the predicted low levels of T3 on these blood tests. Surprisingly, we found the opposite. The T3 levels in the poor responders to T4 actually had higher levels of T3 than those who had a good response to T4.
In the field of endocrinology, if the body’s response to a hormone is blunted despite high levels of the hormone being present, hormone resistance is said to exist. The best known example is insulin resistance which can be found in many of those with diabetes type 2 and obesity. In the case of insulin resistance, insulin levels are very high but the body acts as if there isn’t enough insulin with the result being elevated blood sugar (type 2 diabetes). Could hormone resistance be the explanation of high T3 levels in those who don’t respond to levothyroxine? Or are there multiple ways that people fail to respond to traditional therapy with T4 and in our analysis we identified more of those with T3 resistance than those with the type predicted by Dr. Bianco?
Clearly more research is needed to answer these questions. For now it is important to remember that, even if a simple blood test cannot identify T4 non-responders, a good clinical history and an opened mind should be sufficient to guide the medical provider toward combination T4 plus T3 as a viable alternative treatment of hypothyroidism.