Do you have a Reverse T3 problem?

Reverse T3

Across Canada, Reverse T3 testing is often offered for a fee — patients usually pay for it. It has been this way for more than a few years now.

As patients (and doctors), we need to know when we can save our money and avoid testing Reverse T3 by learning about its elevation indirectly.

Here’s how.

Look for all the signs of thyroid hormone inactivation.

Elevated Reverse T3 levels are just one sign of a high degree of “thyroid hormone inactivation” leading to T3 depletion.

See our infographic and post that explains the big picture of “T3 depletion” in more detail.

Keep in mind that Reverse T3 itself is not evil. It is part of a healthy thyroid hormone metabolism. Every healthy person makes some every day, and that’s why there is a normal reference range for Reverse T3.

However, “excess” Reverse T3, and the bigger picture of thyroid hormone inactivation, IS something that thyroid patients should be concerned about.

There are two major causes of excess thyroid hormone inactivation:

  1. Illness, whether critical or chronic. It can be triggered by inflammation, hypoxia, fasting, protein restriction, severe depression, exercising too hard, or damage to kidney, heart, or cardiovascular system.
  2. Excess T4 from thyroid medication. Your T4 level is above your personal set point right now (even if it is within reference range) and it is triggering hormone inactivation every day you take your pill. This is the only way the human body can try to get rid of the excess T4 that keeps coming in.

When excess thyroid hormone inactivation occurs, your body is trying to lower your metabolic rate. It does this the most effective way possible — by depleting your T3 hormone, which directly regulates your metabolic rate.

Unfortunately, the hormone depletion process is not entirely benign. It can become a runaway train. It can go too far. The process aims to deplete T3, not to monitor how low your T3 goes.

Many doctors assume that hormone inactivation is normal and temporary and is unrelated to our thyroid condition. However, they may not realize that almost all research on Low T3 syndrome has excluded thyroid patients, and because of this, our vulnerability is not acknowledged, and the risk we face is significant.

If T3 goes too low and/or stays low for too long, it is very damaging and puts your health at significant risk.

What to look for

You can see the effects of excess “hormone inactivation” and T3 depletion in your Free T3 and Free T4 blood tests.

1. Lower Free T3 level

This is the biggest sign. When excess Reverse T3 production is occurring, Free T3 levels will be far lower than optimal — in the lower half of reference range, often at the lower end or below.

This is because the very same enzyme that converts T4 into RT3 also converts T3 into T2 at the same time, and the net result of the entire syndrome is T3 depletion.

2. Higher Free T4 level

If you are a T4-treated patient (including desiccated thyroid / DTE / NDT, which is mostly T4), your T4 levels won’t drop much.

Even if an increasing amount of T4 is becoming RT3, you are resupplying T4 to your body every time you take a dose of T4. Your dose can maintain the T4 level, whether Free T4 is mid-normal, high-normal, or over range.

Be aware that in all patients on L-T4 monotherapy, there is an unnatural gap between higher T4 and lower T3, but when hormone inactivation is occurring, the gap gets much larger.

Only if the hormone inactivation rate exceeds your dose (i.e. in severe illness) would you start to drop in your T4 levels as well.

3. What about TSH level ??

TSH level is NOT a sign.  Not at all.  If Reverse T3 is high, TSH will often be low or normal.

Science has known about this for a very long time. In cases of “Low T3 syndrome” in which Reverse T3 is elevated and T3 is depleted, TSH is not elevated but rather normal or low.

Here’s one reason why:

  • TSH rises when your body wants to raise its set point for T4.
  • TSH lowers when your body wants to lower your set point for the most abundant hormone that it senses, whether that’s T3 or T4.

Here’s another reason why: The pituitary pays more attention to the higher hormone level.

  • When Free T4 is significantly higher than Free T3 in their respective ranges, the pituitary gland calibrates mainly to the higher T4 level.
  • When Free T3 is significantly higher than Free T4, the pituitary gland will calibrate to T3 and decrease its secretion.

The human pituitary gland can protect itself in a T3 deficiency. It can survive, if it must, on largely T4 alone, as long as there’s enough T4.  When blood supply of T3 is low, it increases D2 internal conversion from T4 to T3.  When the pituitary gland has its own supply of T3, it really could care less if the rest of your body suffers T3 depletion.

4. The T3:T4 ratio as sign

In T4-monotherapy, or in untreated thyroid patients, excess RT3 can be assumed if you have a huge gap between higher Free T4 and lower Free T3 within their reference ranges.

This is the T3/T4 ratio. It’s easy math.

Divide your T3 number by T4 and see if you get a result lower than 0.23 pmol/L.

  • Free T3 = 3.5 pmol/L
  • Free T4 = 15 pmol/L
  • 3.5 / 15 = 0.23.

The normal ratio in healthy untreated patients with normal thyroid glands is consistently between 0.32-0.38 pmol/L no matter what their TSH, T4 or T3 levels are (see Gullo et al, 2011 which tested a large cohort of over 3800 normal control patients).

A ratio of 0.23 or lower can be evidence of rather poor conversion from T4 to T3.

A ratio of 0.23 can also be a result of the lack of thyroid gland tissue, since this low ratio is the average for athyreotic (post-thyroidectomy patients) who can’t secrete any T3 from their gland.

Extremely low ratios below 0.23 are likely not just due to “poor conversion” rate (sluggish D1 or D2 enzymes responsible for T4-T3 conversion). It’s likely you also have active chronic inactivation of T3 into T2, or genetic defects, on top of that poor conversion.

If your ratio is higher than 0.32 it could be because you’re taking a medication that includes T3, such as desiccated thyroid (DTE/NDT) or a T3-T4 combo. That’s ok. When you have less T4 your body needs more T3 to make up for the T4. When T3 is higher than T4, you can actually achieve optimal T3 without triggering RT3.

5. Expect RT3 to be low if FT4 is low in range

Reverse T3 can only be made out of T4 molecules.

If you don’t have much Free T4, you won’t make much Reverse T3, and RT3 will not show up as elevated in your RT3 test results.

Some reasons your Free T4 may be low (other than being on T3-dominant meds):

  1. You’re simply hypothyroid!  You need a dose increase! This is most frequently the case.  It happens if you are hypo and not diagnosed or treated yet. It happens if you’re slowly increasing your dose and haven’t yet reached optimal levels yet. It can happen if your thyroid gland is being killed off by autoimmune attack. It can happen if you are stuck in an underdosed state due to medical ignorance about how to adjust hormone levels not just normalize your TSH.
  2. You may have an absorption issue interfering with your meds getting into bloodstream. If you’re on Synthroid or another L-T4 medication, look up the full PDF “product monograph” and read the full list of potential interferences with absorption. If your thyroid condition is autoimmune, realize that the gut can also be plagued with autoimmunity: celiac disease, autoimmune gastritis, etc. Some medications may also interfere with gut flora, stomach acid, etc.
  3. Your body may now be only depleting T3, but also inactivating T4 hormone at a faster rate than you’re supplying T4 by oral dosing. Are you chronically ill? do you have a lot of inflammation? Do you have hypoxia from constricted blood flow, low heart rate, or sleep apnea? Whatever is causing this excessive rate of depletion, The T4 from your medication is now going into a bottomless pit, too.  In blood tests, TSH, Free T3 and Free T4 could all be below range, even if your pituitary gland is functional (these blood test results could look like hypopituitarism).

If you’re not sure what is going on, then it may be worthwhile to get a Reverse T3 test, and then calculate your RT3/T3 ratio (a different ratio).

“But my Free T4 is normal or high, so that’s good, right?”

Not necessarily. It could be a bad sign if your TSH is rather low at the same time.

It could be possible in a given patient that 15pmol/L is higher than your current metabolic set point for T4, even if it is within the statistical reference range for T4. If your body wants to lower your T4 set point, TSH will be lower than normal.

You might also be very sick or have chronic inflammation or hypoxia (constricted blood flow, or sleep apnea), and your illness may be lowering your metabolic T4 set point to a ridiculously low level within “normal” range.

Another sign of RT3: Temporary relief from T4 dosing decrease

A few patients’ experience has proven that lowering the T4 dose slightly can reduce the rate of reverse T3 conversion, at least temporarily, if that is indeed one of the triggers causing thyroid hormone depletion.

If adverse cardiovascular symptoms were occurring due to T3 hormone depletion, you could get a reprieve from those symptoms.

In patient experience, cardio symptoms can alleviate for about a week, after which time, they might return if the body is still in “hormone inactivation” mode and considers the lower dose of T4 still “excessive.”

If it does not alleviate hormone inactivation, you may not gain back enough T3 hormone by reducing T4 dose. You could end up more hypothyroid in other organs and tissues (brain fog, fatigue, etc.) if you step back your dose too far.

Ultimately, if the trigger of your T3 depletion was excess T4, not just illness, then lowering T4 can’t be a permanent solution.  You could be stuck between a rock and a hard place without T3 meds: too much T4 depletes your T3, but reducing T4 also depletes your T3.

If this happens to you, you will simply need to take T3 hormone if you want to reduce your T4 levels without becoming hypothyroid. Scroll down to the “Recovery” heading.

Yet another sign: Adverse response to T4 dosing increases

In addition, if thyroid symptoms worsen, especially cardiovascular symptoms like chest pain, within 1-2 days after a T4 dose is increased, that is a sign of acute T3 depletion via hormone inactivation, triggered by a T4 dose above your individual set point and/or illness.

Low Free T3 can create heart and stroke symptoms that mimic Excess Free T3 (See “Low T3’s effects on the cardiovascular system“.)  When T3 levels are extremely low below reference range, this is just as damaging to the cardiovascular system and vascular integrity as excess T3.

If you notice this effect after it happened, now you know why.

CAUTION: Please do NOT try this as an experiment, ever!

If you suspect Reverse T3 based on these signs, raising your T4 dose can be very dangerous, especially if you have a weakened cardiovascular system due to long-term T3 insufficiency!

According to some patients’ experience, once you trigger cardiovascular symptoms by excess T4, you may be plagued with these effects for a long time until you can recover from the “hormone inactivation” phase that you’ve set off.

The half-life of L-T4 is one week. It takes at least a week, if not two, to feel the effects of T4 increases because more of it is converting to T3.

In contrast, rises and drops in Free T3 have an almost instant and direct effect on heart rate, and over hours and days, body temperature.  If chronic illnesses involving inflammation and/or hypoxia as well as excess T4 are conspiring to lower your set point, inactivation can occur at a higher rate.  After acute illness or injury, especially to the heart, T3 levels can drop within hours.

Recovery from T3 depletion

See our separate post on this topic,  “Recovery from T3 depletion

If your method of recovery was successful, you could have been suffering from excess Reverse T3.

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