Take this schematic to an Endo and ask him to review the various potential outcomes when a euthyroid patient does combination therapy or ends up going too high on the exogenous T3. I have tried my best to explain difficult concepts on here but this one I won’t expound on here (opportunity cost of my time) cause it’s complex and a black box I’d argue to everyone on this forum unless they’ve really studied feedback control loop of the HPTA.
I guess the other option is for you to try it and report back your result. Tinkering with both HPG/HPTA when your thyroid is working fine is not a good plan in my opinion.
Figure 2
T4-induced DIO2 ubiquitination in thyroid hormone homeostasis. In response to thyroid hormone signals from the periphery and DIO2-expressing tanycytes, hypophysiotropic TRH-expressing neurons release TRH into the portal blood. TRH is transported to the anterior pituitary gland where TSH is secreted and stimulates the thyroid gland to produce and secrete T4 and T3. Hypothalamic T3 is generated locally by tanycytes and enters the systemic circulation. T3 can also be generated in the periphery via DIO1. In most peripheral tissues, exposure to T4 accelerates inactivation of DIO2 (UbDIO2) and UbDIO2 targeting to the proteasomal system; however, UbDIO2 can be reactivated and rescued fromproteasomal destruction by deubiquitination. Peripheral deiodination is very sensitive to T4-induced DIO2 ubiquitination: a mild increase in the serum T4:T3 ratio favours DIO2 inactivation and decreases fractional T4-to-T3 conversion and peripheral T3 production. However in the hypothalamus, DIO2 is less susceptible to T4-induced ubiquitination than in other tissues. Thus, T4 signalling via DIO2-mediated T3 production is very effective in the hypothalamus, whereas T3 production via DIO2 is easily inhibited in the periphery. Abbreviations: DIO, iodothyronine deiodinase; T2, di-iodothyronine; T3, tri-iodothyronine; T4, tetra-iodothyronine; TRH, TSH-releasing hormone; UbDIO2, ubiquitinated DIO2. Permission obtained from American Society for Clinical Investigation © Werneck de Castro, J. P. et al. J. Clin. Invest. 125 , 769–781 (2015).17