Using rT3 to Assess Hypothyroidism
Controversy Surrounding Reverse T3 (rT3) Measurement
There is polarization about whether reverse T3 (rT3) should be measured to assess hypothyroidism with most traditional Endocrinologists being against its measurement and functional medicine doctors being in favor of it. The normal thyroid gland secretes T4 (an inactive precursor), T3 (the active hormone), and reverse T3, a biologically inactive form 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.
rT3 and 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.
Functional Medicine Perspective on rT3
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. They 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. They 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 him on T3 to try to lower the rT3. They often use a high rT3:T3 ratio as further indication to treat these patients.
Concerns about inappropriate T3 treatment in patients without thyroid disease
Dr. Friedman has seen many of these patients put on thyroid hormone, especially T3, inappropriately. 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 Study on rT3 Measurement in Patients on thyroid hormone treatment (submitted to PLOS One)
Dr. Friedman wanted to know if rT3 was indeed higher in patients on L-T4 preparations and after achieving IRB approval, decided to measure rT3 in 976 consecutive patients who came to see him with potential thyroid problems. 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 24 ng/dL. He did not calculate any type of ratios. Dr. Friedman and colleagues found that the number of patients with rT3 levels above normal range varied significantly with the type of thyroid hormone replacement. The highest rate of an elevated rT3 was 20.9% (29/139) in patients taking T4 alone. 9% (31/345) of patients not taking thyroid hormone replacement had elevated rT3 values. In contrast, only 3.5% (8/226) of patients taking desiccated thyroid hormone with synthetic thyroid had above normal rT3 values, compared to 12% (10/83) of patients taking a T3-T4 combination and 17.4% (24/138) of patients taking desiccated thyroid-T4 combination. Patients on all types of L-T4 treatment had higher rT3 levels than those not on L-T4 treatment (p < 0.00001) and a higher percent of rT3 levels above the cutoff of 24.1 ng/dL (p < 0.00001). Linear regression analysis showed rT3 levels correlated with free T4 and free T3 levels and inversely with log TSH levels.
In conclusion, this study found elevated rT3 levels in patients with symptoms of fatigue on various thyroid hormone replacements with highest levels in L-T4 alone replacement and the lowest levels in those on preparations that contain L-T3. Further studies are needed to understand the implications of elevated rT3 values in patients both on and off thyroid hormone replacement and whether its measurement will be useful in clinical practice to guide thyroid hormone replacement.
Recommendations for rT3 Testing
Dr. Friedman concluded from his study that measuring rT3 is helpful in patients already on thyroid treatments with preparations containing T4 having higher rT3 levels. Most but not all patients on no thyroid treatment have normal rT3, levels so its less helpful in those patients. Patients that have an elevated rT3 on thyroid treatment with either T4 alone or T4 plus desiccated thyroid may benefit from decreasing the amount of T4 given and increasing the amount of T3 or switching to desiccated thyroid extract (DTE).
The concept is in those patients on levothyroxine (L-T4, Synthroid) with a high rT3 you can add on T3 or use DTE that has T3 to “kick out the rT3.” This would lead to improved thyroid function and symptom improvement.
The area of rT3 is clearly an interesting area, and there is a clear division between endocrinologists who do not measure all and the functional doctors who measure it in almost everybody and treat almost everybody for it. Dr. Friedman is hoping that his peer-reviewed article on measuring rT3 is published, there will be more clarity on rT3 measurement.
Ongoing Research and Expert Care
Dr. Friedman is an expert at putting the right patients on the right thyroid hormone. For more information about Dr. Friedman’s practice or to schedule an appointment, go to www.goodhormonehealth.com