The reference range for T3 is not based on a normal (bell-shaped) distribution curve. The values are actually negatively skewed, meaning the majority of the values fall in the upper half of the reference range, and the peak (where the most values lie) is somewhere to the right of the midpoint , and not at the top of the range. This curve suggests that most people’s T3 “sweet spot” may be anywhere from 60-100% of the range. If someone’s optimal dose is at the 60% mark, but they are dosing to 100-120% of range, then the high reverse T3 could very well be from high T3 levels (that are encouraging any T4 to convert to reverse T3 because of increased D3 activity). If someone is taking Natural Desiccated Thyroid (NDT), a decrease in dose may actually reduce reverse T3 by lowering high T3 levels that are triggering the D3 enzyme and reverse T3 production. Since desiccated thyroid contains reverse T3, lowering the dose also eliminates another source of reverse T3. Splitting the dose up so smaller amounts are taken in multiple doses throughout the day may also reduce the reverse T3. Additional T4 could be added to make up for any drop in Free T4 levels if one is taking desiccated thyroid, as long as conditions that favor reverse T3 production (such as diabetes, alcoholism, or others mentioned earlier) are not present. Here is a fact that many will find shocking: A normal thyroid gland produces an average of 100 mcg T4 and 6 mcg T3 daily, although it secretes closer to 10 mcg T3 daily, because some T4 to T3 conversion occurs in the thyroid gland before release. Total daily T3 produced by the body averages 30 mcg, but 80% (24 mcg) of this is from conversion in other tissues.  A 3 grain dose of desiccated thyroid will provide 114 mcg T4 and 27 mcg T3, which closely matches daily thyroid production, but assumes nearly zero conversion. If one has any T4 to T3 conversion (some do and some do not), T4 would need to be added to a reduced dose of desiccated thyroid to mimic normal thyroid production. Gut absorption problems may also affect one’s optimal dose, with some needing higher doses to reach optimal thyroid levels.
Are some people really recovering with T3? Some swear that T3-only therapy gave them their lives back, because anything with T4 (even desiccated thyroid) simply did not work. And then you have people like me, who went “brain dead” on only slightly elevated doses of T3, and many men who ended up with sexual problems because the high T3 levels affected their testosterone and estradiol levels. Perhaps the people who can tolerate high doses of T3 have either: 1) nonthyroidal illness, where the illness itself causes a rise in the D3 enzyme, resulting in high reverse T3 levels and the inactivation of any T3; or 2) genetic differences in the deiodinase enzymes, which would produce drastically different T4 to T3 conversion rates in different people. This is not that far-fetched, with the genetic variations that were referenced above.  An analogy most are familiar with is lactose-intolerance, caused by a deficiency of the lactase enzyme. If you have the lactase enzyme, you can drink a gallon of milk with no problem, but if you’re deficient, well that amount of milk would cause some serious gastrointestinal distress! Perhaps the people who can take extremely high doses of T3 have D1 or D2 deficiencies; those are the deiodinase enzymes that convert T4 to T3, both in the plasma, and at the cellular/peripheral level. If one does not have an enzyme deficiency, then they can quickly become overdosed with the high T3 levels recommended by those who believe in this protocol.
To accommodate these deiodinase enzyme genetic differences, thyroid dosing should be thought of as a continuum with 100% T4 on one end, 100% T3 on the other end, and combinations of T4/T3 in the middle. If this were a normal distribution curve, most people would need a combination of T3 and T4, with the individual T4/T3 concentrations customized for each patient’s biochemistry. Unfortunately, patience is essential in finding this optimal dose, because this is a trial and error process, and changes should only be made every six weeks.
Still questioning the reverse T3 theory and T3-only protocol? Whom to believe? Thoughts on Thyroid internet forums
24. Wendy M van der Deure, Robin P Peeters and Theo J Visser. Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters. J Mol Endocrinol 201044 1-11. http://jme.endocrinology-journals.org/content/44/1/1.full
48. Williams, clinical pathologist, Director of Quality Assurance for Quest Labs in Florida. Phone interview. Oct. 19, 2010.
49. Robertas Bunevičius, Gintautas Kažanavičius, Rimas Žalinkevičius, and Arthur J. Prange, Jr.. Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism. N Engl J Med 1999; 340:424-429. http://www.nejm.org/doi/full/10.1056/NEJM199902113400603