Reverse T3 Test (rT3): Dr. Friedman’s New Publication Shows it’s Important To Measure it in Patients With Hypothyroidism.
What is Reverse T3?
There is a lot of controversy about whether reverse triiodothyronine (rT3) should be measured to assess treatment in hypothyroidism. The normal thyroid gland secretes T4 (an inactive precursor), T3 (the active hormone), and reverse T3, a biologically inactive isomer of T3 that may block T3 from binding to the thyroid hormone receptor. Most of the circulating T3 is derived from 5′-deiodination of circulating T4 in the peripheral tissues by type 1 deiodinase. Deiodination of T4 can occur at the outer ring (5′-deiodination), producing T3 (3,5,3′-triiodothyronine), or at the inner ring, producing reverse T3 (3,3,5′-triiodothyronine) by type 3 deiodinase. Type 2 deiodinase in the pituitary also converts T4 to T3 and is regulated differently from type 1 deiodinase.
Sick Euthyroid Syndrome
Many years ago, endocrinologists realized that in severe illnesses, type 3 deiodinase increases and rT3 is often high and T3 is often low. Endocrinologists termed this “sick euthyroid syndrome” and noted that it was common in many types of chronic illnesses, especially in patients hospitalized in intensive care units. It was usually recommended that these patients not be treated with thyroid hormone and in most cases, the elevated rT3 resolved when the patients’ health returned.
How Do Most Endocrinologists Treat Hypothyroidism?
Most endocrinologists treat patients with hypothyroidism with levothyroxine (known as L-T₄), including different brands such as Synthroid and solely monitor treatment based on the blood test TSH. Multiple studies have shown that about 15 to 20% of patients on levothyroxine with a normal TSH still have symptoms of hypothyroidism and these are the patients that see Dr. Friedman. Thus, solely measuring TSH may be inadequate to get a good understanding of the patient’s thyroid status.
Dr. Friedman realized many years ago that many patients with hypothyroidism need individualized treatment such as using levothyroxine plus liothyronine (L-T3), or desiccated thyroid, like Armour thyroid or NP thyroid. These patients often feel better with an improvement in their hypothyroid symptoms. Conventional Endocrinologists now often use levothyroxine plus liothyronine, but they are reluctant to use desiccated thyroid due to misinformation like there is variability between lots and it isn’t FDA-approved (most thyroid preparations are not FDA approved).
Recent Trends In Reverse T3 Measurement and Testing
However more recently, more alternative doctors, including doctors who used to be known as antiaging doctors and now are called functional medicine doctors, have made quite an issue about rT3. In contrast, most Endocrinologists do not believe in measuring rT3. The functional medicine doctors argue somewhat appropriately that high rT3 is bad and can block T3 from binding to the thyroid hormone receptor. They also state that rT3 can go up in various conditions including systemic illness, stress, inflammation, chronic pain, dieting, weight gain, and depression.
Issues With Treating Patients Solely Based on Reverse T3 Test
Functional medicine doctors often quote articles showing that these diseases are correlated with a high rT3, but do not necessarily show that the rT3 plays a significant role in the disease. These functional medicine doctors rely extremely heavily on rT3 to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe them T3-only preparations to try to lower the rT3. They have not published on whether this is effective or not and may treat a person with completely normal thyroid function tests and put the patient on T3 to try to lower the rT3. They often use a high rT3: T3 ratio as further indication to treat these patients.
Individualizing Hypothyroidism Treatment:
Dr. Friedman realizes that hypothyroidism treatment needs to be individualized and that many patients on the standard treatment don’t do well. They need individualized treatment such as using levothyroxine plus liothyronine, or desiccated thyroid. However, Dr. Friedman is very cautious about starting patients on thyroid medicine, which often shuts down the body’s own thyroid hormone production.
He has seen many patients put on thyroid hormone by functional medicine doctors, solely due to a high rT3 or high rT3 to T3 ratio, they are often put on T3 alone. T3 does not penetrate the brain well, not nearly as well as T4 does, and these patients often suffer from hyperthyroidism systemically and hypothyroidism in their brain. Dr. Friedman also believes that a healthy thyroid works best on its own and prescribing exogenous thyroid hormones to a patient with a normal thyroid gland, causes the gland to stop making its own hormones. Sometimes it is very hard for the patient to stop thyroid hormones, especially if given in high enough dose or for a long period of time. Therefore, he is quite cautious about who he puts on thyroid medicine and who he does not.
Dr. Friedman’s New Publication in PLOS One
Dr. Friedman decided to measure rT3 in almost 1000 consecutive patients who came to see him with potential thyroid problems over an 11-year period. All of these had signs and symptoms of hypothyroidism, and many of them were already treated with different thyroid preparations. He used the upper limit of normal for rT3 at either Quest or Labcorp, which is usually 24 ng/dL. He did not calculate any type of ratios in this publication..
Dr. Friedman and his team found that patients taking the standard medication, levothyroxine, were more likely to have high levels of reverse T₃. By contrast, patients on other therapies that included T₃—such as desiccated thyroid extract (DTE) or L T₄ plus liothyronine (L-T₃)—had much lower levels. The findings suggest that standard treatment may not work equally well for everyone.
“I was inspired to figure out why my patients with underactive thyroid levelss aren’t doing well, even though they’re on what’s considered optimal thyroid hormone replacement,” said Dr. Friedman. “I wanted to look at this older test and see if it can explain why these patients have fatigue.”
Reverse T₃ is often viewed as outdated and rarely tested in conventional medicine, but Dr. Friedman believes it’s worth reconsidering. “There are articles that came out saying we shouldn’t be measuring this,” he said. “But the test is important, especially in patients who aren’t doing well on optimal replacement.”
Key discovery for Thyroid Testing
One of the study’s more surprising discoveries was just how common elevated rT₃ levels were in patients on L-T₄-only therapy. “Most of the high reverse T₃ was seen in those patients,” Dr. Friedman said. “People not on any thyroid medicine usually had pretty good levels.”
What Does the Study Show, and Will There Be a Follow-Up Study?
The study doesn’t claim that high reverse T₃ is the direct cause of fatigue, but it opens the door to more personalized treatment strategies. Dr. Friedman plans to follow up with a study that tracks patient symptoms alongside rT₃ levels to better understand whether changing medications guided by rT₃ levels can improve quality of life.
Why Should You Make an Appointment to See Dr. Friedman?
Dr. Friedman combines research and patient care so his patients with hormone problems can feel better. He is one of the few Endocrinologists, who not only measures rT₃, but knows how to use it to optimize thyroid hormone replacement. If you have hypothyroidism, are not feeling well and want to use Dr. Friedman’s expertise, please schedule an appointment at goodhormonehealth.com. Similarly, if your doctor won’t measure rT₃, but want to use it to adjust your thyroid hormone, please also schedule an appointment.
Can I Read the Article or Find Out More About the Study?.
The full study, “Reverse T3 testing in patients with hypothyroidism on different thyroid hormone replacement,” is available now in PLOS One or at goodhormonehealth.com, where you can also read the press release. You can listen to his webinar about this paper at https://www.goodhormonehealth.com/webinars/
or https://www.youtube.com/watch?v=AEdzJ71CFUY or on Dr. Friedman’s Podcasts on spotify, apple podcasts, iheartradio, podcastidex, and amazon music. Search for Theodore Friedman.