I recently consulted with a man in his sixties who had a 35-year history of chronic fatigue and a 20-year history of depression and anxiety. He had been diagnosed with hypothyroidism about 30 years ago, for which he was prescribed Synthroid (levothyroxine). He was also taking three different psychotropic medications, which were prescribed by his psychiatrist. Several months previously, laboratory tests had revealed an elevated thyroid-stimulating hormone (TSH) level, with normal T4, and a T3 level below the reference range. Based on the high TSH level, his Synthroid dose was increased, which normalized the TSH level, while T4 remained normal and T3 remained below normal. Unfortunately, the increase in the Synthroid dose did not help his fatigue or depression, and it seemed to make his anxiety worse.

Based on the patient’s laboratory tests, it seemed that he had an impaired capacity to convert T4 to its biologically active metabolite, T3. The conversion of T4 to T3 depends on the action of deiodinase, an enzyme that catalyzes the removal of one iodine atom from T4. Two such enzymes, deiodinases 1 and 2, occur in humans. Common variants of the genes for each of these enzymes have been identified,^{1 2} and there is circumstantial evidence that some of these variant genes code for the production of a functionally defective enzyme. I suggested to the patient that he might do better with a thyroid preparation that contains both T3 and T4. I was not in a position to write the prescription myself because I am no longer in clinical practice. So, I suggested that he discuss this possibility with his doctors.