Reverse T3 in Patients With Hypothyroidism, Helpful or a Waste of Time?

Background: Reverse T3 (rT3) is a biologically inactive form of T3 that is created by peripheral 5 deiodination of T4 by type 1 and type 3 deiodinases and may block T3 binding to the thyroid hormone receptor. As about 15% of patients on L-T4 replacement with a normalized TSH report continued fatigue and other hypothyroid symptoms, efforts are needed to understand why this occurs and how it can be corrected. Decades ago, endocrinologists realized that in severe illnesses, rT3 is often high and T3 is often low and termed this “sick euthyroid syndrome”. However, more recently, alternative doctors, including functional medicine doctors, have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor. Without peer-reviewed publications, these functional medicine doctors rely heavily on rT3 levels to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe them L-T3-only preparations to try to lower the rT3. Also poorly characterized in the literature are the effects of hypercortisolism and hypopituitarism, both of which should modulate the expression of deiodinases to increase rT3. Hypotheses: 1) Patient rT3 levels will vary significantly with the type of thyroid medication taken. 2) Patient rT3 levels will be clinically significant in the management of patients on thyroid medications. 3) Hypercortisolism and hypopituitarism will increase rT3 levels. Methods: The most recent rT3 measurements were analyzed from 621 patients currently being managed by TCF. The upper limit of normal for rT3 at either Quest or LabCorp, which is usually 24.1 ng/dL was used as a cut-off for a high result and below 9.2 ng/dL as the low cut-off. Results: Elevate rT3 levels was seen in 3% of patients of patients not on thyroid replacement (5/143), seen in 8% of patients (17/203) taking desiccated thyroid. It was more prevalent in patients taking desiccated thyroid with synthetic T3 (27%, 7/26) or T4 (15%, 16/104) and was seen in 15% of patients (9/58) taking synthetic T4 alone. Changes were made to the amount or type of medications in 199 patients. Levels of rT3 levels were outside the normal range in 27% of these patients (54/199), being above normal range in 16% of these patients (32/199). Hypercortisolism was seen in 37 patients, 36 from Cushing’s disease, however above normal rT3 was seen in only 2 patients. Hypopituitarism was diagnosed in 22 patients, only one had above normal rT3 levels because they couldn’t afford their growth hormone replacement. Conclusion: Measuring rT3 may be helpful in patients who are already on thyroid treatments, and is of greater importance in patients taking synthetic preparations. It is not recommended in patients who are not taking thyroid medicine (even if experiencing hypercortisolism) or in patients with hypopituitarism that are taking adequate hormone replacement.