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.

The patient was pleasantly surprised by my recommendation. He remarked that around 25 years ago he was not doing well on Synthroid, as it made his chronic fatigue much worse. He consulted a holistic doctor who switched him to liotrix (brand name, Thyrolar®), which contained both levothyroxine (T4) and triiodothyronine (T3) in a 4:1 ratio. While on liotrix, he had no fatigue and no side effects, and all of his laboratory tests for thyroid function stayed in the normal range. He continued on liotrix for a number of years and did “extremely well” (his words). However, the holistic doctor moved to a different state, and the patient was unable to find another doctor willing to continue the liotrix prescription. So, he was forced to go back on Synthroid and has felt bad ever since.

I told the patient that his compelling story, combined with his subnormal T3 level on the lab test, should be enough to persuade any reasonable physician to agree to a trial of switching to liotrix. Out of an abundance of caution, the switch could be done gradually; perhaps one-third of the dose every two to four weeks. Unfortunately, I was wrong; the psychiatrist and the patient’s primary care physician were both unwilling to approve a trial of liotrix.

I found this hard to understand. Here the patient tells his doctors exactly what he needs, and he provides laboratory evidence to back it up. Did the doctors just not listen to him? Or maybe they did listen, but didn’t believe him. Or maybe they believed him but were unwilling to risk the consequences of deviating from whatever “standard of care” they were locked into by whoever it is that dictates “standards of care.” It is true that the research is conflicting on whether patients fare better with T3/T4 than they do with T4 alone. However, those studies likely included at least two different types of patients: those who did not need T3 and felt worse when they took it, and those who did need T3 and felt better when they took it.³ Averaging the results from those different types of patients would lead to the erroneous conclusion that T3 therapy is not helpful for anyone. One would think that an open-minded doctor would allow compelling clinical and laboratory evidence to overrule the conflicting results from research.

Or maybe the doctors did not want to put in the extra time that would be required to become proficient in managing hypothyroid patients with a T3/T4 combination (Carlton Fredericks often remarked, “People tend to be down on what they are not up on.”). A lack of proficiency would be a particularly weak excuse for the psychiatrist because there is a long history in psychiatry of using T3 to treat depression. Or maybe the doctors were skittish because liotrix is no longer commercially available, so it has to be compounded by a compounding pharmacy.

Whatever their reasons were for refusing to try T3, these doctors lost an opportunity to help a long-suffering patient who had fallen through the cracks of modern medicine. Practicing high-quality medicine requires taking your patients seriously, even if what they tell you falls “outside the box” of what you have been taught. From my personal experience as a practicing physician, I would venture to suggest that there is great joy to be found outside of that box.