Can you discuss the consensus report on identifying a subset of patients with hypothyroidism who fsaol to achieve optimal symptomatic resolution with LT4 monotherapy; and, therefore, should be considered for combination T4/T3 combination therapy?
The vast majority of patients With hypothyroidism do well on levothyroxine alone, but there is a significant percentage of patients who do not do OK. And it really depends on the way we look at these patients. We can find residual symptoms that can be attributed to hypothyroidism all the way up to 30-40% of the population. It is debatable whether these symptoms are indeed secondary to hypothyroidism or due to confounders comorbidities. Patient's perception. Um, again, most of the symptoms of hypothyroidism are really as specific, and it's incredibly difficult to sort out these symptoms, particularly in a In a disease condition which is chronic uh and uh it's very slow progressing. So it's very difficult to define when the patient was doing OK. All said The, uh, this situation, uh, it's something that we need to deal with, uh, as a specialist, uh, and as a provider. And, uh, denying, uh, uh, The reality that patients are not doing fine, uh, uh, doesn't bring uh anywhere. And actually can cause, uh, uh, disaffection of patients and can prompt patients to look for mm, very, uh, shall we say, wild and uh unproven therapeutic approach which can result uh in real, uh, um, in real morbidity. So, uh, the, um, theoretical, uh, reason, uh, to consider, uh, combination therapy whereby we define combination therapy, a mix of, uh. T4 and T3 derives by the fact that uh the thyroid hormone production, uh, the, the thyroid hormone production from the thyroid gland is a mix of T4 and T3. And so in patients who are devoid of endogenous production of thyroid hormone, the entire pool of thyroid hormone derives from exogenous synthetic T4 that then is metabolized in peripheral tissues in T3. That, uh, uh, again, that works well in most of the patients. But there are some um measurable differences between endogenous production of thyroid hormone and exogenous thyroid hormone replacement, particularly in patients who have absolutely no endogenous thyroid hormone production, meaning patients who underwent a thyroidectomy for, for an example. In these cases, uh, um, there is pretty good evidence that in order to achieve a normalization of TSH, the 3T4 tends to be slightly higher. And the T3 levels in circulation tend to be a bit lower compared to what would be. A basal state, a normal state if you want to call it normal. So this is uh uh some evidence that uh uh yes, we're very good uh in normalizing TSH. In the aggregate, we're very good uh in making patients feeling OK. But we do not know. Whether this is a Exactly what we want to achieve in terms of Complete normalization of thyroid hormone and most important, whether we can ascribe some symptoms to the lack of the endogenous production of T3 or to the fact that uh uh we are administering thyroid hormone through the um gastrointestinal system rather than direct secretion in the blood. And that's obviously something we, we do not know. So, to this end, uh, uh, there has been some, uh, um, some intense studies, uh, in the, uh, experimental setting, experimental meaning, uh, in animal, in experimental animals. And, uh, uh, that goes back to 1990, 1994 when Doctor Morella Escobar clearly demonstrated that, that, uh, in, uh, rats that uh are made uh hypothyroid. The restoration of serum level and tissue levels of thyroid hormone, meaning the ratio T4 and T3, could be achieved only by combination therapy, whereby, by, uh, adding some T3 to the levothyroxine uh uh treatment. And that has prompted a series of experiments, clinical experiments to see whether this combination could relate to symptoms. And signs of hypothyroidism in patients and the data are a bit all over the place. Uh, there is a question uh uh from the perspective of the methodology employed in the studies on the numerosity of patients in the studies, meaning the risk of not achieving enough, uh, um. Statistical power, um, multiple, uh, differences in study design which make it very difficult to, to ascertain. Whether the lack of significant uh differences uh is due to um lack of power or uh uh lack of effectiveness of uh multiple uh um combination therapy. But patients often are not doing well, and that according it really depends on how that measured again it can be all the way up to 40% if we want to look for some any symptoms ascribable to hypothyroidism, and patients are vocal and patients expect that we do something about it. So, uh, at this point, uh, we need to decide what do we do next? Uh, how do we go? What are the boundaries of, uh, uh, our therapeutic intervention. And most important, uh, um, how can we prevent to cause hydrogenic, uh, uh, morbidity.
