I recently found an excellent 2015 article focusing on the phenomenon of “poor conversion” from T4 to T3 thyroid hormones in hypothyroid patients treated with thyroxine (T4, Synthroid).
- Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015). Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. Endocrine Connections, 4(4), 196.
Their study was based on 353 subjects on T4-only therapy who had reached a stable “euthyroid” status (defined as TSH <=4.0 and fT4 >10pmol/l). Their subjects were divided into three categories:
- patients who had had carcinoma (who had had thyroid surgery and were taking a large dose of T4 in order to suppress TSH),
- patients with “AIT” (autoimmune thyroiditis), and
- patients who had had non-cancerous “Goitre” (after surgery to remove thyroid nodules).
The results showed that people with less of a functioning thyroid gland had the lower conversion rates. The carcinoma group had the poorest conversion rate.
They also showed that if AIT or Goitre patients take higher and higher doses of L-T4 per kg of body weight, they risk depressing their T3 levels further if they are a “poor converter.”
Wow. The authors openly blame T4-only therapy for poor conversion status:
While acknowledging the role of genetically determined differences in deiodinase activity affecting conversion rates, the poor converter status described here
appears to emerge mainly as a consequence of the T4 monotherapy itself, induced by the mechanisms discussed above (42, 43, 44, 45). Compared to untreated subjects,
deiodinase activity and conversion efficiency tend to be diminished in L-T4 treatment (20, 22).” (p. 203)
The authors also emphasize “the inhibitory actions of … reverse T3 (rT3) on deiodinase type 2 activity (27).” (p. 202)
Question: Based on the effect of rT3 on slowing D2 deiodinase-based conversion, would it not be logical to infer that T4-T3 conversion might get poorer and poorer the longer you stay on T4 therapy and gradually build a higher rT3? There could be a cumulative effect over time.
The researchers also explain the phenomenon of some patients who have chronically low T3 levels regardless of increased L-T4 dose:
Central and peripheral regulatory mechanisms do not constitute divided levels of control, as has previously been assumed. Rather they are integrated via feed-forward control of deiodinase activity by TSH and operate jointly to maintain T3 homeostasis as an overarching goal (30). (p. 202)
Based on this theory of T3-homeostasis, if one increases the L-T4 dose in a person who is maintaining a very low T3, it would make the Low-T3 problem worse in many ways:
- More T4 intake is not likely going to raise T3 levels in a “poor converter,” and thus it does nothing to help those body tissues already starved of sufficient active hormone T3.
- By raising T4 intake past a certain point, one may be artificially suppressing their TSH (so they’re probably more hypothyroid than TSH lab test results will show).
- By raising their free T4, deiodinase D3 will create more RT3 out of it
- Now their body has not only more Reverse T3 but also lower TSH, which further inhibits the secretion of T3 from the minimally-functional thyroid gland.
Due to competition between Reverse T3 and free T3, the ratio between them matters. In the presence of an already very low fT3, it may be truly dangerous to one’s health even to have Reverse T3 in a “normal” lab reference range.
- The serum fT3 levels may be deceptively high: there may be more fT3 in the blood that cannot enter cell nuclei due to inactivation by D3 as soon as it enters the cell.
- Hypothyroidism levels could vary across the body. In a given organ, it is difficult to determine what percentage of T3-receptors could be “blocked” by inactive Reverse T3.
- Certain organs are especially dependent on T3 serum levels and if these are low, they are likely to suffer the most from T3-starvation, such as blood vessels and the heart.