Reverse T3 in patients with hypothyroidism on different thyroid hormone replacement.

The rate of elevated rT3 varied significantly by type of thyroid hormone replacement, with the highest rate in patients taking T4 alone.

• 20.9% (29/139) of patients taking T4 alone had elevated rT3 levels above the upper limit of normal (24.1 ng/dL)
• 9% (31/345) of patients not taking any thyroid hormone replacement had elevated rT3
• Patients on all types of L-T4 treatment had higher rT3 levels than those not on L-T4 treatment (p < 0.00001)
• The percentage of rT3 levels above the cutoff of 24.1 ng/dL was also higher in patients on all types of L-T4 treatment compared to those not on L-T4 (p < 0.00001)
• 976 consecutive patients with symptoms of fatigue treated for hypothyroidism in a private Endocrinology practice were included

Patients on L-T3-only preparations had the lowest rT3 levels among treatment groups.

• Preparations containing L-T3 alone were associated with the lowest levels of rT3
• This finding is consistent with L-T3-only treatment bypassing T4-to-rT3 conversion via peripheral deiodination
• rT3 is created by peripheral 5 deiodination of T4 by type 1 and type 3 deiodinase enzymes (D1 and D3)

rT3 levels correlated with free T4 and free T3 levels and inversely with log TSH levels.

• Linear regression analysis was used to assess correlations
• rT3 levels showed a positive correlation with free T4 levels
• rT3 levels showed a positive correlation with free T3 levels
• rT3 levels showed an inverse correlation with log TSH levels

Approximately 15% of patients on L-T4 replacement therapy with a normalized TSH report continued fatigue and other hypothyroid symptoms.

• This statistic is cited as a known clinical problem motivating the study
• The persistence of symptoms despite normalized TSH is a key reason for investigating rT3 as a potential contributor
• Functional medicine doctors have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor

rT3 was measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) and the upper limit of normal rT3 of 24.1 ng/dL was used as the cut-off for elevated levels.

• Initial rT3 measurements were retrospectively analyzed from initial blood tests in 976 consecutive patients
• TSH, free T3, and free T4 were measured by electrochemiluminescence immunoassay (ECLIA)
• The study was conducted in a private Endocrinology practice
• All patients had symptoms of fatigue and were being treated for hypothyroidism