What does THYROID have to do with ALLERGY? (Part 2)

reverse t3 thyroid testing Feb 27, 2023

Several doctor friends have recently expressed an interest in my method for optimizing thyroid for allergy, or any patients who don’t feel well and would like to. Here are the technical details of how I manage patients I suspect have this thyroid imbalance problem. See part 1 to discover why I think this is important.


Hormones are a complex subject. Today’s blog will address thyroid in as concise a way as possible without leaving out important details, but of course thyroid is only one component of the very complex human endocrine system, without which we would not be alive. This discussion is aimed at physicians. Please remember that while I am a physician, I am not your physician, and this is not medical advice. Please seek the attention of your physician for any medical condition you may have. I am unable to answer individual questions about medical care outside a doctor-patient relationship.


Last post we discussed elevations in Reverse T3 and how that can block thyroid function. There are several situations that trigger elevations in reverse T3. The one I think I personally have is a genetic defect in the 5'deiodinase enzyme that produces T3, so my body was making too much of the blocker, reverse T3. The reason Armour thyroid worked for me is that it has an 80/20 ratio of T4 to T3, which for some people is about right.  RT3 synthesis is a parallel pathway and is overproduced in that scenario by a different enzyme. 


RT3's metabolic/ evolutionary purpose is to protect us:

  • From hyperthyroidism in Graves or other situations of thyroiditis.
  • In a starvation or severe illness/injury situation to slow our metabolism down to block T3 so we don't just burn up all our calorie stores. This is seen in critically ill patients in ICU and in that scenario is called “Euthyroid Sick Syndrome” or “Nonthyroidal Illness”. 


There are several other situations that can trigger elevations of RT3:

  • When people fast it shoots up and is very slow to come back down. It's a big reason why calorie restriction diets fail so often. This may be a main mechanism for shifts in "Metabolic set point".
  • I have seen it in patients after gastric bypass as well, and is also responsible for a good deal of the weight regain issue these patients face. 
  • Consistent lack of quality sleep, or OSA.
  • Chronic stress, and adrenal dysfunction.
  • I have seen one patient where it happened because she took botox for headaches and it seeped down and paralyzed her ability to swallow for several months. She went on tube feeds but it was already too late. It took almost 2 years for her to wean back off thyroid medication after this incident.
  • For some reason beta blockers also trigger this, Amiodarone, ADHD medications as well.
  • One last thing- too much Synthroid. (T4) Consistently I see people on way too much. And their freeT3 is low normal and RT3 is high. Some thyroid medications can also be contaminated with Reverse T3. Since the FDA thinks it is an inactive metabolite, it is not regulated as a contaminant.
  • And there are others.


Laboratory diagnosis is key! 

When you check RT3 it's important to know that it is protein bound, the same as most endogenous thyroid hormones. There's no test for Free RT3. So you can't compare directly with FreeT3. The only accurate way I know is to also draw a total T3. The ratio of Total T3 divided by RT3 should be calculated. The ideal is between 10-14 or so, the lower or higher it is from that range the worse and more symptomatic the patient will likely be. The absolute value of RT3 should never get below 8. Those folks don't feel good either. Free T3 can range from 3.3 or so to maybe 4.0 at the highest without causing sleep disruption. Free T4 should actually be at the lower end of the normal range, 1.1 or lower.


I almost never give people T3 alone for a longer term. But will frequently start there if the ratio is poor. I've seen it as low as 2. Those people feel like crap and think you walk on water when you fix them. The idea here is that you drive TSH down with T3, which reduces endogenous T4 while also supporting metabolism. Keeping the levels as even as possible is important - giving it twice or 3 times daily because of the short half-life. As TSH falls, so does endogenous T4, thus reducing Reverse T3 by lowering the metabolic precursor. The T4 level staying at the lower end of the normal range consistently allows for an eventual reduction of RT3 production, and the patients begin to feel better after several weeks, or sometimes it takes even longer.


I generally use Liothyronine. (Synthetic T3) Sigma generic is good, others including Sun and Mylan not so much. Mylan has actually been shown to be contaminated with RT3 at some point. The branded Cytomel is fine but very expensive. It is also important to stay with the same manufacturer, as actual T3 content can vary up to 30%, and a change of generic can take a previously well-balanced patient back into symptoms and imbalance. 


It is also important to start small and move up slowly. 1/2 of a 5 mcg Liothyronine tablet at first and they have to take it twice a day because the half-life is short. I tell them 6 am and 4 pm, or some variation of that, or as close to a 12-hour dosing interval as possible. To cut off the highs and lows that affect TSH stimulation and increase RT3 production.


And because taking it at bedtime is a recipe for no sleep. And of course, absorption is best on empty stomach or at least nothing with soy or Calcium. Most will also need some Levothyroxine but not nearly as much as is traditionally given to thyroid patients. 25 mcg twice a day same

schedule as the T3 is typical or even 1/2 of 25. The same issue exists with T4  with variations

In strength between manufacturers and even different lots of the generics and even synthroid sometimes. I see people all the time do poorly after a new batch comes in. Their pharmacy needs to pick one and stick with it.


I also use a fair amount of Armour-desiccated thyroid and find it helpful in many cases. It contains a 4:1 ratio of T4 to T3, which works well in many cases. 60mg of desiccated thyroid contains 38mcg of T4 and 9mcg of T3 and is easily broken in half or even fourths. Not so much good luck with NP thyroid, but this may have changed lately as it has become more popular. But don’t let the pharmacist tell your patient that NP thyroid is a “generic” for Armour. The carrier sugars vary between these 2, and they also contain different levels of Thyroglobulins and other carrier proteins that can stimulate antibodies in autoimmune thyroiditis, Hashimoto’s in particular, and sometimes even measurable levels of Calcitonin. So I don’t use desiccated thyroid if a patient has measurable anti-TPO or anti-Thyroglobulin antibodies. (Hashimoto’s autoimmune thyroiditis).


While on treatment, patients will have fairly wide swings of lab values throughout the day. This is in contrast to the assertion that Levothyroxine has a 2-week half-life. This erroneous assumption happened because of how long it takes for Radiolabeled Iodine to clear once given and incorporated into the protein bound thyroid hormone in the gland. Absolutely not so with thyroid replacement. So l ask them to have the labs done as close to 6 hours after the morning dose as possible if they are taking thyroid hormone twice daily. This generally works out to between 11 and 1 pm, but the key is consistency. They also need to use the same lab each time, as protocols and reference ranges vary as well. Those swings in hormone levels, particularly if they are taking T4 Levothyroxine once a day, trigger more RT3 production, another reason I think BID dosing works better.


In regards to lab reference ranges:

2 standard deviations from the “normal” mean is much too wide. And normal in my experience very likely includes a decent proportion of patients who are actually symptomatic but with undiagnosed thyroid dysfunction, so is suspect. My ideal ranges are as follows:


TSH - can vary depending on whether the patient has a growing thyroid nodule or other condition where suppressing TSH is desirable. If not, 0.5-1.0 is ideal. Anything over 2 is not good. Two SD above normal is actually around 3, so why does the "normal range" go up above 4? Good question.

Free T4 - .8-1.0 is ideal.

Total T4 - no need to order this, nor FTI or any other estimate lab.

Free T3 - 3.3-3.8 is pretty ideal, keep in mind can swing quite a bit even with mild differences in lab draw time or meds taken time.

Total T3 - The only reason I am drawing this is for comparison with Reverse T3. That said, if the value is below 100 or over 200 I know I am going to find an overdosing/ underdosing issue or a ratio that is really OFF. The reason for the wide variations is the wide range of thyroid-binding proteins that will occur, depending on a patients’ nutrition and steroid hormone status, and other factors.

Reverse T3 - once again, must be ordered in conjunction and at the same time as the Total T3, for the same reason. Absolute values should not be less than 8, and if over 20 indicates a dysfunction for one or more of the reasons mentioned above. 


This is the typical lab set I ask of my patients Every Time we check. And when things are off and we are adjusting meds, I will repeat in 8 weeks after a change in meds. 


Baseline labs also include a thyroid autoantibody panel that includes: Thyroid peroxidase antibody, thyroglobulin antibody, and either Thyroid receptor antibody or Thyroid stimulating Immunoglobulin if they have had a suppressed TSH in the past.


If you find this fascinating, please check out THE NEW ENDOCRINOLOGY lecture series, a deep dive into all aspects of thyroid and other hormone management, available 


Thyroid autoimmune disease is another interest of mine that is pretty much ignored by mainstream rheumatologists AND endocrinologists, and a topic for another day. Thank you for your kind attention. 

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