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 only what Iraq's in alone, but there is a significant percentage of patients or do not do okay. And it really depends on the way we look at these patients. We can find uh residual symptoms that can be attributed to hypothyroidism all the way up to 3040 of the population. It is debatable whether these symptoms are indeed secondary to hypothyroidism or due to confound ear's comorbidities, patient's perception. Again, most of the symptoms of hypothyroidism are really specific and it's incredibly difficult to sort out the symptoms of, particularly in a in a disease condition which is chronic. And it's there is low progressing. So it's very difficult to define when the patient was doing okay. All said, the this situation is something that we need to deal with as a specialist and as a provider and denying a the reality that patients are not doing fine, doesn't bring anywhere and actually can cause this affection of patients and can prompt patients to look for very uh shall we say, wild and unproven therapeutic approach which can result in real uh real mobility. So the theoretical reason to consider a combination therapy whereby with a fine combination therapy, a mix of T. four and T. three. The rise by the fact that the thyroid normal production Uh the paranormal production from the Tarot Gland is a mix of T4 23 and so in patients were devoid of indigenous production of tara doorman. The entire pool of Tara Jarmon derives from exogenous synthetic T four. The den is metabolized in peripheral tissues in tea tree that again, that works well in most of the patients, but there are some measurable differences between endogenous production of tyra dormant and the exogenous paranormal replacement, particularly in patients, were absolutely no indigenous paranormal production, meaning patients who underwent thyroidectomy. For, for an example, in these cases, there is pretty good evidence that in order to achieve normalization of TSH, the Free T four tends to be slightly higher and the T three levels in circulation tend to be a bit lower compared to what would be a basil stage, a normal state if you want to call it normal. So this is uh some evidence that yes, we are very good in normalizing TSH in the aggregate were very good in making patients feeling okay, but we do not know whether this is a exactly what we want to achieve in terms of Complete normalization of Tara doorman. And most important, whether we can ascribe some symptoms to the lack of the indigenous production of T. three or to the fact that we are a ministering tyra doorman through the gastrointestinal system rather than direct secretion in the blood. And that's obviously something we do not know. So to this end, there has been some some intense studies in the experimental setting, experimental meaning in animal, in experimental animals. And uh that goes back to 1919 1994 when dR Morales escobar clearly demonstrated that in rats that are made hypo thyroid, the restoration of serum level and tissue levels of tyra doorman, meaning the ratio of 34 23 could be achieved only by combination therapy, whereby by adding some tea tree to deliver to Iraq's in treatment. And that has prompted a series of experiments. Clinical experiments to see whether this combination could relate to symptoms and science survival, terrorism, impatience and the data are a bit all over the place. Uh This question from the perspective of the methodology employed in the studies on the numerous city of patients in the studies, meaning the risk of not achieving enough uh statistical power, multiple differences in study design, which makes it very difficult to ascertain whether the lack of significant differences is due to um lack of power or a lack of effectiveness of multiple combination therapy, But patients often are not doing well and that according, it really depends on how that measures. Again, it can be all the way up to 40 if we want to look for some any symptoms, a describable to hypothyroidism and patients are vocal, and patients expect that we do something about so at this point, we need to decide. What do we do next? How do we go? What are the boundaries of our therapeutic intervention? The most important? How can we prevent too? Cause I estrogenic morbidity?