Also, as a refusal of your statement, you may want to read this meta-analysis that report both sides of the T3/T4 debate:
In mammals, the majority of active thyroid hormone (T3) within cells is derived not directly from T3 in the circulation, but indirectly from T4, via the action of the D2 deiodinase (29, 30). The concentration of circulating T4 is about five times higher than T3 and it is the circulating T4 rather than T3 that serves as the main source of thyroid hormone for the body (5). In addition a proportion of serum T3 is also derived from serum T4 (5). These considerations have been used as a key theoretical argument against the use of LT3 in the management of hypothyroidism.
However, serum thyroid hormone levels may not entirely reflect intracellular thyroid hormone status. Via variation in uptake, activation and metabolism of T4, cells can modulate intracellular T3 levels independently of circulating thyroid hormone levels. Downstream control by thyroid hormone transporters such as MCT8 and MCT10, the deiodinases (DIO2,DIO3), and transcription co-factors locally modify thyroid hormone bioavailability and action at the intracellular level. The potential for dichotomy between serum thyroid hormone levels and intracellular action is dramatically illustrated in reports of individuals with rare mutations in the MCT8 transporter (Allan-Herndon-Dudley syndrome) or the thyroid hormone receptor alpha (present in many tissues but not the hypothalamus/pituitary) (31, 32). Here, marked tissue-specific hypothyroidism is seen with dramatic effects on bone and brain development despite “normal” or even raised serum thyroid hormone levels (31, 32). The effects of more common variants are less clear.
At the same time evidence has been accumulating of tissue-specific regulation of thyroid hormone contents in tissues via differential expression of thyroid hormone transporters and iodothyronine deiodinases (29, 33). It has been hypothesized that LT4 monotherapy may not restore intracellular T3 levels in the brain in all patients and this may explain the dissatisfaction some patients have on LT4.
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.
I have read it and its not a refutation of my feedback to you. I was giving you a different perspective based on relevant experience. Because maybe 1-5% of hypothyroid patents (estimate) may do better on combination therapy does not justify a euthyroid person doing combination therapy. You are not hypothyroid. Hypo patients would give their left testicle or ovary for your fT3/fT4 ratio (these are without thyroid meds, correct?).
Can I understand what relevant experience you’re referring to? Just to know who I am talking to (a doctor, an endocrinology student, someone passionate about the subject ecc).
I’m not on thyroid meds, I did a trial 3 years ago with Euthyrox monotherapy before TRT and felt horrible. I still remember the body aches I was getting and the inability to recover from trainings.
Ditched it in the trash and started TRT.
My TSH has been creeping up during the past months and this paired up with the cognitive function decline I’m experiencing, despite the proper amount of androgens in the body. I basically match all the cognitive sides associated with hypothyroidism.
What would you do then if a patient was coming to you, with everything else in check, but with symptoms of hypothyroidism? Would you shrug your shoulders and say you are perfectly fine, there’s nothing I can do for you.
This reminds of the docs that were telling me that a total T of 300/400 ng/dL is perfectly normal and that androgens are not an issue.
My relevant experience on these medications and my knowledge of the subject. I am a simple anonymous stranger on the internet.
I notice feedback on here that agrees with what the poster wants to do is always much more welcomed than throwing a wrench in said plans, but I figured i would give you a different perspective.
I wish you the best and hope things work out for you.
Didn’t say I feel I’m rare, quite the opposite actually.
But you’re extrapolating what you want from that quote.
They wrote: “The potential for dichotomy between serum thyroid hormone levels and intracellular action is dramatically illustrated in reports of individuals with rare mutations in the MCT8 transporter”.
It doesn’t mean it doesn’t happen to average Joe, it means it can happen to a less degree to normal people and it has been reported anecdotally many times, but it is clearly obvious in people with the Allan-Herndon-Dudley syndrome.
Wait, I’m in the same position as you. No medical degree in anything medical related, but just passionate about the subject and I had to drag myself out of the hole incompetent doctors threw me in. So I want to listen to all the opinions and I understand your positions.
We had Ksman and phisiiolojic in the past that played doctor and messed up people, so you need to accept the fact that people don’t take what you say as the Gospel, but rather want to have a conversation about it.
And as I said, I was following the same exact school of thoughts you;re preaching (and still do to a certain degree), but following ranges just left me symptomatic and made me waste 2 years and a half on TRT.
We won’t fully know the effects for this until we can properly quantify T4 to T3 conversion in specific tissues. The variability of said conversion may be dramatic and T3 receptor sensitivity by tissue may be quite variable.
I understand the need to feel better, so I wish you the best on your journey. I felt compelled to share with you as I have been down this road (you may have a very different outcome) and I think the advice that gets shared on here to run up your TT and fT3 levels (without acknowledging the risk with the benefit) is irresponsible.
Ignorant people I can understand giving this advice after reading some internet articles, but there’s MDs out there giving people supra levels of Test and shooting their fT3 above range. Comes back to objective function and sustainability of outcome (1. short-term performance vs 2. longevity vs 3. compression of morbidity-somewhere in between).
I am well aware :-). I think at this point some just see my screen name and skip because the details are not as entertaining as reading/watching some of this internet stuff.
I understand your concerns and as I said I agreed with your view in the past, but let’s say you were having your testosterone numbers great on paper, but you were symptomatic like me when in range. You go slightly above range (i’m not talking about 2000 ng/dL of T and a free T of 50) and you start seeing symptoms fading away. What would you do? Contemplating a piece of paper telling you how good your numbers are for the rest of your life and feel junk, or have a couple of values marked in red on your blood work and finally starting feeling normal?
I agree with you that TRT is overly prescribed and I’m one of the few with a clear diagnosis of secondary hypogonadism at age 27, being basically unable to function. I’ve tried everything to restart my HPTA before committing to TRT for life, so I can’t say I’ve left anything untried.
And I eventually experienced on a 3 years journey that I feel ok when I cross the “normal range” in terms of androgens and estrogens levels.
Would you consider me irresponsible? Are you able to guarantee that I’m doing harm to myself?
Regarding thyroid, I’m not willing to go above range at all. Just trying to bring both T4 and T3 higher to see if it solves cognitive issues. It’s a trial. If it doesn’t, the thyroid is not the issue and I’ll keep looking for a possible cause.
Just an anecdotal data point, I have full blown Hashimoto’s thyroiditis with TPO/thyroglobulin antibodies through the roof. I had/have no cognitive sides either before of after treatment. Moving rT3 from 28 to 6 did nothing (mood, temperature, energy, etc).
Without clinical experience I think a lot of us thinkers can get in our head we’ve got something that perhaps we do not. Again, not referring to you specifically, maybe just me.
No judgment from me, we are two different people. I was providing some alternative feedback and discussion of risk vs reward. The more time on here the more I like @mnben87 's suggestion of using Hitchen’s Razor. We are two different people, take my time and info I provided as a sign of love/care from an internet stranger and some food for thought to be cautious as you experiment with your HPTA/HPG.
Note Testosterone controlled by HPG which is coupled with HPTA.
