Endocrine Society and the American Thyroid Association, seeing tens of thousands of patients and seeing the importance of these minor 12.5 microgram differences that were alluded to.
The Carr study has been criticized. It's not an optimal study, I would agree, but it is one of the only ones we have. The importance there was that TRH was not used to stimulate TSH. TRH was just another test assessing the physiologic level of those patients. They were looking at TRH tests. That was not really the criterion.
There is indeed a well-established correlation of the extent of clinical disease, hypothyroidism, with TSH elevations. It's as evident as that high blood pressure causes strokes and heart attacks. It hasn't been studied because it's so self-evident to endocrinologists.
And the differences that were alluded to in some of the studies, yes, TSH will vary and thyroid function will vary, and it depends on whether we're talking about acute administration or chronic. It's a matter of dose and duration. A 12.5 microgram difference in thyroxine over years will cause atrial fibrillation,