✅Evidence-Based: Written by a Board-Certified Endocrinologist
In Comments and Controversies on Hormones Demystified, I laid out the case for why I needed to write this series of posts about T3. In this and other articles on the topic, I address the myriad claims and questions that have come up over the years in the Comments section of T3 Or Not T3 – Exploring The Controversy. Per my current Comment policy, I will aggressively moderate reader-generated content that doesn’t meet the standard. I would also ask you to restrict your thoughts, questions, and theories about T3 to the narrow subject of each post in the T3 Controversies Series. I believe this will make the reader experience better for everyone, allowing people to more easily find the information they need. Let’s get started on today’s subject! [HD: Note that today’s post has a lot of footnotes. I encourage you to read them, as I address many questions you may have in those.]
Question: When T3 (liothyronine) is added on to T4 (levothyroxine) therapy, how much T3 should I take1?
HD: I plan to keep the scope of my answer to this common question extremely narrow, as the topic lends itself to getting lost in the weeds. For the purpose of this discussion, we will focus on T3 add-on therapy – not desiccated thyroid hormone2 or T3-only therapy.
Focus on Normal Physiology First
In order to provide context for what a reasonable dose of T3 might be, it is critical to understand how much T3 is produced in euthyroid people3. Without getting into a detailed physiology lesson, the thyroid contributes roughly 5 micrograms (mcg) of T3 to the body’s pool, with the rest produced by peripheral conversion of T4 to T3 by deiodinase enzymes. The D2 enzyme (brain, pituitary, muscle, heart, brown adipose tissue) does the bulk of the heavy lifting, producing about 20mcg of T3 per day. The D1 enzyme (liver, kidney, thyroid) contributes a small amount to the T3 pool, about 5mcg/day4.
If my readers weren’t so intelligent, I’d probably just do a mic-drop after the preceding paragraph and call it a day. I know y’all wouldn’t be satisfied with that, but humor me for a minute, simply as a thought exercise. I’ve written extensively about widespread misconceptions regarding “conversion issues” and debunked alt med’s assertion that there are millions/billions of people out there who can’t make adequate amounts of T35.
The bottom line is: should someone have a specific defect somewhere along the pathway of thyroid hormone production, metabolism, transport, and/or action, their body will most likely compensate for that defect. Remember that the body is excellent at achieving and maintaining homeostasis; it can increase T4:T3 conversion, decrease thyroid hormone breakdown, increase thyroid hormone transport into the cell, upregulate thyroid hormone receptors, and increase thyroid hormone binding to receptors.
What About People Who Have No Thyroid?
What the body cannot do, however, is secrete T3 from the thyroid if the thyroid has been surgically removed. Therefore, I’d like to use that situation to form the basis of what might be a reasonable T3 dose. If the thyroid contributes about 5mcg of T3 per day, then it stands to reason that a dose delivering 5mcg should be a good starting point for most thyroidectomized people6.
In order to figure out how to deliver 5mcg of T3, I’ll paraphrase one particularly critical comment on my original T3 post: “What you put in your gob is not what you get in your blood.” This is more true for levothyroxine than for liothyronine, but it’s good to at least be familiar with the bioavailability of these drugs. Under perfect conditions (empty stomach and no interfering medications or food), about 80% of a levothyroxine dose is absorbed. Liothyronine has significantly better bioavailability – about 95% of a dose is absorbed, even in the presence of food.
Therefore, a 5mcg liothyronine pill will deliver 4.75mcg of T3 into the blood – pretty darn close to replacing the 5mcg that the absent thyroid was responsible for making.
At this time, I’d like to bring the discussion back around to my earlier, tongue-in-cheek implication that thyroidal T3 production is all you really need to know when choosing a dose of liothyronine. It is my opinion (based on published data as well as clinical experience) that people with postsurgical hypothyroidism are more likely than other subsets of hypothyroid folks to benefit from T3. I believe that this is due to loss of thyroidal T3 secretion and (for some people) the presence of the Thr92Ala SNP in the D2 gene7.
My point is: loss of thyroidal T3 production is likely to be the biggest “hit” the body can take when considering what could go wrong along the entire pathway of thyroid hormone production, metabolism, transport, and action. Any other defect in the pathway – consider re-reading my post about EDCs and impaired thyroid hormone action, for example – will likely provoke a compensatory response by the body.
Therefore, it is my opinion that hypothyroid people who seem to require T3 supplementation should rarely require more than 5-10 micrograms per day.
But I Take More Than 5-10 micrograms of T3!
It is my opinion8 that the vast majority of people taking T3 do not truly need it. As such, many folks on T3 have been misdiagnosed as “non-converters” or even diagnosed inappropriately with hypothyroidism. When using a short half-life hormone such as T3, the body may perceive it as a stimulant, assuming that it is not truly needed as a replacement therapy. As with any stimulant, the initial good feeling tends to wane over the course of weeks to months. This often results in an endless cycle of dose escalation, which temporarily makes people feel better…until they gradually drift back toward baseline.
While the above explanation likely accounts for most people who inappropriately take higher doses of T3, I can think of some valid – but rare – reasons and one less-than-rare reason why people may require more.
First and most common, a large person with an absent thyroid may need a larger dose of T3. I don’t want to get mired in whether to use actual body weight or ideal body weight to calculate thyroid hormone dose requirements, because reality has taught me that the required dose is usually based on a number somewhere between actual and ideal weight. Suffice it to say that a tall person with a fair amount of body mass could conceivably require more than 10mcg per day of exogenous T3.
The trouble with the rest of the “reasons” for a higher T3 requirement is that they should be extraordinarily rare, but they’re typically invoked will-nilly by alt med enthusiasts who really want the thyroid to be the answer to their problems. I wrote about one such scenario in T3 Controversies: Can Impaired Thyroid Hormone Action be Treated with T3? In that post, I addressed the potential effects of Endocrine Disrupting Chemicals (EDCs) on thyroid hormone metabolism and action. I recommend (re)reading the whole post for context, but here is an excerpt elucidating the pitfalls of claiming “I need high-dose T3 because…EDCs:”
[Y]ou simply cannot invoke a “block” at a single point in the thyroid hormone metabolic pathway as the sine qua non of needing to give large doses of T3. Even multiple blocks in the pathway by different types of EDCs might not cause enough of an effect to be clinically apparent. The human clinical data in this space are thin, so I will have to explain my opinion on this matter using a combination of my clinical experience and knowledge of physiology.
In my opinion, here are the necessary conditions that would need to exist in order to see EDCs cause clinically meaningful hypothyroidism:
• The person has hypothyroidism, making them unable to ramp up production of thyroid hormone if required.
• The person has a high burden of EDCs with constant or recurrent exposure.
• Multiple different EDCs present in high concentrations will cause multiple blocks at different steps in the synthesis, conversion, transport, and intracellular action of thyroid hormone.
• These blocks will – at least at some of the steps – be complete or near-complete blocks, likely due to the high blood EDC concentration.
• Compensatory actions taken by the body will be inadequate due to the number and completeness of the blocks, thereby failing to increase thyroid hormone action at the cellular level.
I hate to beat a dead horse, but you must remember that the body has numerous mechanisms by which it can compensate for a deficiency or block in one or more parts of the pathway. So my usual answer to someone who thinks they’re special enough to fall outside the above guidelines is, “You don’t need high-dose T3 because…homeostasis.”
What About People with a Thyroid?
I’ve focused mainly on people with postsurgical hypothyroidism, because I believe that is the subset of hypothyroid people more likely to respond to T39. However, I do have patients with postablative hypothyroidism10 and autoimmune hypothyroidism11 who sometimes benefit from T3 add-on therapy.
In my opinion, the usual reason why fewer people in these latter categories will truly need T3 is because their thyroids are still capable of producing some. Obviously, the ability to produce T3 will correlate with how much thyroid tissue destruction has occurred. Hypothyroid people whose thyroids were completely destroyed by radioactive iodine might be more likely to benefit from T3. Similarly, those with Hashimoto’s might benefit from T3 once the majority of the thyroid has been destroyed.
Coming back to the main point of this post: regardless of what type of hypothyroidism you have, if you haven’t seen any benefit by the time you reach 10mcg of T3, it’s time to seriously reconsider whether you’re on the right path. If you continue to escalate the dose of T3 with no improvement or an improvement that wanes over weeks to months, T3 is almost certainly not the answer for you.
By using this site and interacting with me and others in the Comments, you agree to abide by my Disclaimer. As a reminder, please restrict your comments and questions to the narrow topic at hand. There are plenty of opportunities to discuss additional hotly contested topics in my other posts in the ongoing T3 Controversies Series.
- Today’s focus is on the total daily dose of T3, not how to divide up the doses. Note that optimal dosing of T3 would be accomplished via a sustained-release preparation, which is not currently commercially available. Therefore, T3 should be dosed 2-3 times/day.
- Most versions of desiccated thyroid hormone have a ratio of T4:T3 in the neighborhood of 4:1.
- This term refers to having normal thyroid function.
- The absolute numbers I’ve given will vary slightly depending on the source you read. I pulled my numbers from this source. Also keep in mind that the numbers will get smaller or larger with lighter or heavier people, respectively.
- Please read everything in the Thyroid category on this site before asking questions about conversion issues; I’ve covered this ground in numerous posts. If I haven’t covered your specific conversion-issue question yet, I probably will in a future T3 post.
- Keep in mind that people with postsurgical hypothyroidism may adequately compensate for the loss of thyroidal T3 via any of the mechanisms outlined in the preceding paragraph. This explains why only a small subset of these folks seems to do better with T3 add-on therapy.
- I discuss this single nucleotide polymorphism in more detail in Is TSH the Best Test?
- This opinion is based on years of weaning people off of T3, only to find that they feel no different off of it.
- Note: I am not saying these folks need T3; most will do fine with levothyroxine alone. But in those who do not feel well on T4 alone, they may benefit from adding T3.
- Previously treated with radioactive iodine for hyperthyroidism, leaving them with a non-functional or partially functional thyroid.
- Hashimoto’s thyroiditis