We examined relationships between
thyroid hormone (TH) metabolites in humans by measuring
3,5-diiodothyronine (3,5-T2) and
3-iodothyronamine (3-T1AM) levels after
liothyronine administration. In secondary analyses, we measured
3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and metabolites were documented for 96 h after a single dose of 50 mcg
liothyronine. In 18 patients treated for
hypothyroidism,
levothyroxine therapy was replaced by daily dosing of 30-45 mcg
liothyronine. Analytes were measured prior to the administration of
liothyronine weekly for 6 weeks, and then hourly for 8 h after the last
liothyronine dose of the study. In the weekly samples from the hypothyroid patients,
3,5-T2 was higher by 0.033 nmol/L with each mcg/dL increase in T4 and 0.24 nmol/L higher with each ng/dL increase in FT4 (p-values = 0.007, 0.0365). In hourly samples after the last study dose of
liothyronine, patients with T3 values higher by one ng/dL had 3-T1AM values that were lower by 0.004 nmol/L (p-value = 0.0473); patients with
3,5-T2 higher by one nmol/L had 3-T1AM values higher by 2.45 nmol/L (p-value = 0.0044). The positive correlations between weekly trough levels of
3,5-T2 and T4/FT4 during
liothyronine therapy may provide insight into
3,5-T2 production, possibly supporting some production of
3,5-T2 from endogenous T4, but not from exogenous
liothyronine. In hourly sampling after
liothyronine administration, the negative correlation between T3 levels and 3-T1AM, but positive correlation between
3,5-T2 levels and 3-T1AM could support the hypothesis that 3-T1AM production occurs via
3,5-T2 with negative regulation by T3.