What laboratory and/or clinical features, especially persistent symptoms, suggest the need for combination therapy—including with a DTE—to optimize management? What have trials evaluating patient preferences suggested about combination therapy?
The patient population that may respond or may be the target for therapeutic treatments beyond levothyroxine. Usually are patients that do not feel OK on levothyroxine alone. Do not have any obvious underlying comorbidity that can explain their not feeling well. And, um, And usually they are requesting this therapy. Very seldom providers prompt themselves to start a different type of formulation. So, uh, generally speaking, uh, the patients initiate the request to do something about it. And again, uh, uh, symptoms can be very, uh, disabling from the patient's perspective, and they, they need to be addressed uh uh by the provider. Another, uh, um, I would call it, uh, um, circumstantial evidence that may lower the threshold, uh, from the provider's standpoint to initiate, uh, alternative treatments is the observation of low T3 levels in patients, uh, uh, that are treated with levothyroxine alone. Again, uh In the absence of symptoms, I would be hardly hard pressed to make any therapeutic change. But if the patient is not doing well and I see a lower T3 level, T3 level low low or below normal range, that would probably prompt me to consider alternative treatments. The problem of going on alternative treatments, particularly when we Add uh T3, which is leotyronine, is that the current formulation of leotyronine uh require uh. If we look at the pharmacokinetics, twice a day administration. We, uh, have experimental evidence that the, uh, leotyronin has a very, uh, short, uh, um, equilibration phase in its pharmacokinetics. Equilibration phase means, uh, that, uh, the, uh, Immediately after absorption, the leotironin is rapidly distributed in the serum pool, resulting in a rise of T3 level, often above normal range. And then a relatively quick disappearance from serum. That uh causes peaks and troughs of uh uh T3 levels if we are giving a relatively high dose on a single daily administration. So if our goal is maintaining a relatively steady level of T3, we should look for a twice a day administration. In terms of dosing, currently available doses of leotyronine are 5, 25, and 50 mcg. The usual dosing of leotironine is everywhere between 2.5 and 5 mcg on twice daily administration. This is really not carved in stone. Uh, the only, um, the only society that gives some degree of recommendation is the European Thyroid Association. Which aims to the equivalent of 3.75 mcg twice a day, which is very difficult to achieve in um In the setting of what we have here in the United States. Um One, once, uh, we decide to go on, uh, uh, combination therapy, we also may want to consider, uh, uh, whether using, uh, um, desiccated thyroid extracts. Desiccated thyroid extracts have been around since 1851. And, uh, uh, they were the primary way of treating, uh, uh, patients with hypothyroidism. One thing that we need to recognize is that those are thyroid extracts, meaning that the content of T3 is higher as compared to the circulating levels of T3 in the ratio T3 to T4 in circulation in humans. So even the cicaded thyroidexacts, which are definitely natural. Uh, are not as physiological as we'd like them to be. And the ratio of T4 to T3 to T4 is skewed toward a relative higher presence of T3 as compared to what would be normal in circulation in humans. When it comes to assessing the success of the therapy, then we need to look at two different parameters. One is Serum thyroid hormone and TSH levels and then comparing these parameters with the patient's symptoms.
