Recovery from T3 depletion

T3 DepletionThis post is a continuation of these posts

In this post, I explain how to recover (or help a patient recover) from T3 depletion.

  • Part 1: When illness is the trigger
  • Part 2: When L-T4 dose is the trigger
  • Part 3: Oversenstivity to T4 medication after recovery

Part 1: When illness is the trigger

a) If you have a healthy thyroid gland

If critical illness and Low T3 do not conspire to kill a patient (and they can and do), they can recover naturally — IF they have a sufficiently healthy thyroid gland.

Patients with healthy thyroids would not be taking L-T4 hormone therapy, so their T4 level will naturally drop during illness.

Then, at the beginning of the “healthy-thyroid” person’s recovery phase

  1. Their body’s set point for T4 will rise.
  2. The pituitary gland will then temporarily secrete more TSH to stimulate the thyroid gland, which then secretes both T4 and T3 hormone. (see Peeters et al 2005, Discussion section)
  3. Free T4 levels will rise before Free T3 levels in bloodstream. This is because T3 is still being broken down into T2. The thyroidal secretion compensates for some T3 loss, but it will take some time to build up Free T3 levels in bloodstream.
  4. The temporarily elevated TSH stimulates Deiodinase Type 2 to convert more T4 into T3, which rebalances the T3:T4 ratio.
  5. When T4 thyroid hormone levels are sufficient, TSH will normalize.

The rise in TSH (step 2) and the healthy thyroid gland play key roles in the early phases of the recovery from illness: “an increase in serum TSH drives the rise in T4 and marks the onset of recovery” and “The centrally initiated increase in TSH secretion was followed by a recovery of the peripheral metabolism” (Peeters et al 2005).

Peeters et al 2005 found these differences in T3 levels among survivors and non-survivors on the last day of their time in intensive care:  Survivors had a Total T3 average of 63.0 [48.7–79.2] ng/dL, while non-survivors had Total T3 of 54.5 [42.2–70.1]. The laboratory reference range for Total T3 was 92.8–162.9 ng/dl. Non-survivors’ T3 hardly rose at all during their time in Intensive Care, but survivors’ T3 levels rose. However, both categories of patients still had an average Total T3 that was below reference range — they still had not recovered their T3 levels by the time they died or were released from intensive care.

Therefore, the next logical question is, in critical illness, “What happens …

b) If you do NOT have a healthy thyroid gland

Let’s say you are a critically ill thyroid patient, and you depend on L-T4 medication.

You’ve either had a thyroidectomy, or your gland is so damaged that you have been taking what could be considered a “full” replacement dose of L-T4. The hospital dutifully maintains your thyroid hormone dosage and maintains TSH in normal range.

Unfortunately, the staff is not likely watching your T3 levels.

According to science’s current theory of Low T3 syndrome, these are the challenges you will likely face during recovery:

  • your T4 dose may be above your body’s set point in illness and this excess may maintain the rate of T3 depletion.
  • Your TSH will not rise to stimulate your remaining thyroid gland (if you have any) as long as your T4 dosage locks TSH in its place.
  • Although you may have normal or even high T4 levels from T4 dosage,
    • it may not be converting to sufficient T3, and
    • you may lack living thyroid tissue that can secrete “enough” T3 for recovery.

How can anyone think a smooth recovery is going to be easier for the thyroid patient on L-T4 monotherapy than for the person with the healthy thyroid gland?

What if some of us really do need T3 medication to recover, or else we are at higher risk of death?

But as of today, it appears we only have three studies to test whether these unfortunate implications of the current theory are true in clinical practice. Only one of these studies examined an “acute illness” setting in which T3 fell low, and that study enrolled SIX hypothyroid men on Synthroid who were good converters before their surgeries.

Why don’t we know enough?

Because thyroid patients are excluded from study of “nonthyroidal illness” / Low T3 Syndrome! Read more about it: Thyroid Patients Excluded from Research

But don’t lose hope! There is a solution.

Can L-T4 monotherapy help in “non-thyroidal illness”?

Help? No.

We’ve known about T4 therapy’s ineffectiveness in this situation for a very long time (see Brent & Hershman, 1986).

Even the 2014 ATA guidelines for the treatment of hypothyroidism agree on this point — no benefit and “safety concerns that limit support for this approach” (Jonklaas et al, 2014, sec 22a)

Why? Giving any patient, even a person with a normal thyroid gland, may mean that extra T4 either does nothing, or it makes Low T3 lower.

During the depths of Low T3 syndrome, the body’s hormone metabolism is currently disposed to reject T4. In this state,

  • The body considers it “excess” T4 because it is above the patient’s set-point.
  • Very little T4 can convert to T3 while D1 and D2 are downregulated.
  • Too much T4 gets broken up into Reverse T3 while D3 is upregulated.

If you add more T4 in this state,

  1. it goes into a bottomless pit, and
  2. it can feed the fire of reverse conversion and deplete even more T3.

Can T3 therapy help in “non-thyroidal illness”?

Yes it may, if doctors are strategic about it.

T3 does not require either D1 or D2 to activate it. It’s already active.

Yes, it’s safe, even in critical illness because:

  • There is little chance the patient will go hyperthyroid on T3 … unless you grossly overdose them. Currently, the patient’s T3 is lower than their set point.
  • The 2014 ATA guidelines by Jonklaas et al (sec. 22b) found in their review that there was no harm linked to trials of T3 treatment in this situation as long as doses were not excessive.

Key points:

  • The main challenge is to overcome the speed at which T3 gets converted into T2 while the patient’s body is in reverse-conversion mode, while not shocking their sensitive body. Intravenous delivery helps to prevent sudden rises in T3 levels that can occur with delivery in pill form.
  • If you are giving T3 intravenously, it will be more potent than it is when oral dosing. Gross and Pitt-Rivers, the discoverers of T3 hormone in 1952, found in early testing that oral doses were approximately 80-90% as potent as injection.

One would hope that the patient’s body responds well to the therapy as they recover. Ensure that T3 does not rise too high in the later stages of recovery.

An example of therapy

In the study of Low T3 in critical illness by Peeters et al, 2005 (Patients and methods section),

Sixty-two patients had been treated with thyroid hormone at some point during the course of their critical illness. Treatment was initiated when

  • they had a serum T4 concentration below 50 nmol/liter in the face of a normal T4-binding globulin level
  • and concomitantly clinical symptoms of hypothyroidism, defined as coma or central nervous system suppression, failure to wean from the ventilator, or hemodynamic instability, which were unexplained and resistant to conventional supportive therapy.

In these cases, thyroid hormone treatment consisted of

  • an iv bolus of 150 μg T4 daily
  • plus 0.6 μg T3 per kilogram of body weight per 24 h as a continuous iv infusion.

Unfortunately, Peeters et al did not evaluate the effective of this combined T4/T3 therapy in patients in their article. They did not state how many of the 71 patients who died received this therapy, nor how long patients had been on this therapy before they either died or were released from intensive care.

Their omission of this data is surprising since thyroid therapy logically could have influenced thyroid hormone levels reported in their results tables, and readers would naturally be curious about whether this therapy was effective in aiding recovery.

However, given the data provided in Peeters et al’s study, it is possible that some patients who were put on this T4/T3 therapy regime still died. Those with lower T3 levels were more likely to be chosen as candidates for this therapy, given their criteria. Peeters et al reported that RT3 levels increased in non-survivors from Day 1 to Day 5 and again increased by Day 15, and “In patients who did not survive, there was a substantial increase in rT3 levels on the day they died.” Non-survivors’ T3 was slightly lower, on average, than it had been on Day 1 of admission to intensive care.

If any number of Peeters et al’s patients on this therapy died, it could be explained by these factors:

  • The onset of therapy may have been delayed for too long since patients’ eligibility for it was based on a Low T4 value, not a Low T3 value.
  • The addition of 150mcg T4 to a patient who had not been taking any before (only 3 patients were taking any thyroid hormones upon admission) might have triggered an even higher rate of conversion to RT3.
  • The T3 dose given along with their T4 might have been insufficient to overcome the rate of T3 depletion.
  • Given that the therapy was a static dose, their T3 dose was apparently not increased, nor was T4 dose decreased with sensitivity to their changing T3 and RT3 measurements over time.

Part 2: When L-T4 monotherapy is the trigger

What if a patient is likely suffering from chronic T3 depletion at least partly due to their T4 dose?

The scientific theory already suggests the following therapeutic strategy:

  1. Lower the L-T4 dosage to remove this trigger of T3 depletion.
  2. Add T3 hormone dosage to fix the T3 deficit as soon as possible. Low T3 is hypothyroidism. A transition to T3 monotherapy is the fastest way to recover, since it completely avoids the inactivation of T4 into Reverse T3.

If this recovery method is effective, you will see a patient’s RT3 levels decrease and T3 levels rise. Symptoms of T3 deficiency alleviate, and thyroid balance returns.

After recovery, prevent this depletion from recurring by maintaining the patient on L-T4/T3 combination therapy that results in a healthier T3:T4 ratio, keeping both hormone levels within the patient’s set-point.

Because combination therapy often puts T3 higher in range than T4 in their respective reference ranges, it will be easier for the patient to achieve optimal T3 levels without having a higher T4 trigger T3 depletion again.

Doctors and patients have already been doing this in clinical practice for a long time, and it is advised on the patient-run STTM website.

Part 3: Oversensitivity to T4 medication after recovery

After recovery, what if you try to return to your former T4-based therapy, but symptoms and signs of T3 depletion return?

You might experience an adverse and extreme response to a lower level of T4 than you were taking before — such as angina (cardiovascular chest pain), which has been reported in studies especially among the elderly with cardiovascular disease (Ellyin et al, 1986; Myerowitz et al, 1983; Trescoli-Serrano & Tulloch, 1998).

Despite a normal yet not too high T4, your T3 level may drop low again. In that case, you might now be oversensitive to T4 hormone dosing and need to lower the dose.

In thyroid patient experience, this has been known to happen in rare cases, even after many years of apparently “successful” T4-based therapy. A “low-normal” amount of T4 in your medication could now be excessive and deplete your Free T3 again.

Get your Reverse T3 tested. It can help you know what’s going on.

  • See if Reverse T3 is high in range or elevated despite mid-range or higher Free T4, and/or
  • See if your T3 / Reverse T3 ratio is okay.

What’s a good T3: RT3 ratio?  Peeters et al calculated the ratio with both Total T3 and RT3 measured in ng/dL. They found that this ratio was still very low on the last day in intensive care among those who died (average 0.61 [range 0.39–1.23]), compared with those who survived (2.54 [1.57–3.82]).  Keep in mind this ratio was calculated with Total T3, not Free T3.

If Reverse T3 is excessive and your Free T3 is depleted, you may need to adjust your T4/T3 ratio in combination therapy so that you can raise your T3 without triggering depletion by a higher T4.

If it’s not “excess hormone inactivation” happening, then you could now be oversensitive to T4 for another reason, such as a cardiovascular system that is now very weak and oversensitive after chronic T3 depletion.

Whatever the cause, if someone’s body refuses to convert T4 into sufficient T3, they will never achieve optimal T3 levels on L-T4 monotherapy.

  • Some patients may need to live on a higher ratio of T3 to T4 based on their lower tolerance for T4 hormone. Higher amounts of T3 can suppress the TSH due to the T3 dosing effect.
  • Others may need to be completely reliant on T3 medication alone, as a last resort. Patients have survived and thrived even without TSH or T4, but they usually have to take 3-4 smaller doses of L-T3 per day to maintain T3 levels at a relatively steady state. See “Rationale: L-T3 monotherapies

What thyroid patients need

This is why we are campaigning for all thyroid patients’ access to T3 thyroid hormone should they require it.

  1. We all may need access to T3 hormone to recover from a critical or chronic illness without a fully functioning thyroid gland.
  2. Some patients may need a T3-T4 combination therapy to prevent T3 depletion from happening again.
  3. Some patients may become oversensitive to T4 and may not be able to return to their former mode of therapy, requiring more T3, or even 100% L-T3 monotherapy.

Browse our Campaign Statement

7 thoughts on “Recovery from T3 depletion

Leave a public reply here, on our website.

This site uses Akismet to reduce spam. Learn how your comment data is processed.