A highlight in the concepts that I gathered at 2016 American Thyroid Association meeting in Denver Colorado includes the documentation that low T3 is associated with worse health measures and for the persistent hypothyroid symptoms in patients treated with levothyroxine or T4. In a lecture given by Dr. Elizabeth McAninch from Rush University, she traced the history of how we had evolved thyroid treatment from dessicated thyroid hormone to current levothyroxine monotherapy ( no T3) since the 1970’s, when it was discovered that our own tissues are able to convert t4 to T3, the active hormone. Guidelines since then suggest that only levothyroxine monotherapy be given to patients who need thyroid hormone replacement. Levothyroxine is also Synthroid, Unithroid, Levoxyl, Tirosint, L-thyroxine. So everyone who requires full thyroid replacement after thyroidectomy or after radioactive iodine treatment, or thyroiditis needs to rely on their own personal peripheral conversion of levothyroxine to get their T3, the active form of thyroid that works on the tissues and the brain. The body does this with an enzyme called deiodinase 2, a seleno-protein. We have recently learned that some individuals have genetic alterations (polymorphisms) of this important enzyme which make the enzyme less active, and patients who carry these mutations may be particularly at risk of tissue hypothyroidism if given only levothyroxine after they become hypothyroid.
We, as endocrinologists, often see many patients treated for hypothyroidism that continue to have hypothyroid symptoms despite having “normal” thyroid tests. It is on these patients that I have actively tried combination T4 and T3, or disiccated thyroid hormone. The larger question that needed an answer was whether patients that are treated with levothyroxine alone are actually different from normal individuals. Dr. McAninch showed research that answered the question. She presented data obtained from NHANES data, a large population of 10,700 patients treated with levothyroxine, and compared them to 10,000 people who did not require thyroid replacement. Amazingly, in contrast to normal controls, patients with hypothyroidism treated with levothyroxine alone had lower serum free T3, total T3, and free T3/free T4 ratio levels. They are heavier with higher BMI. They were more likely to be on statin therapy to manage their high cholesterol. More likely to be on beta blockers to manage higher blood pressures. More likely to be using anti-depressants for anxiety and depression. They consumed lower calories per day despite having higher body mass. They also had less movements.
This large body of data makes thyroidologists very aware that levothyroxine alone is not sufficient therapy to return hypothyroid patients to a normal state. Based on these and other data not discussed here, new protocols are being designed to randomize patients to 3 types of thyroid replacement treatments to determine which may be best: levothyroxine alone, combination of levothyroxine and liothyronine (T3), or desiccated thyroid (naturethroid). From Dr. Francisco Celi’s studies we have learned that 25-30 micrograms of T4 is equivalent to 10 micrograms of T3. This replacement will be used when adding T3 in the combination arm of the study. For example for someone on 150 micrograms, the new dosing would be 125 micrograms of levothyrxine and 10 micrograms of liothyronine or T3. The study principal investigators are Dr. Celi from U of Virginia, Dr. Cappola from U of Penn, and Jackie Jonklass from Georgetown University. Its about time we took a broader look at this very important issue!
A cogent review is found in the following reference!