Biosynthesis of 3-iodothyronamine (T₁AM) is dependent on the sodium-iodide symporter and thyroperoxidase but does not involve extrathyroidal metabolism of T₄

3-Iodothyronamine (T₁AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T₁AM is an extrathyroidal metabolite of T ₄. This study uses an isotope-labeled T₄ [heavy-T ₄ (H-T₄)] that can be distinguished from endogenous T ₄ by mass spectrometry, which allows metabolites to be identified based on the presence of this unique isotope signature. Endogenous T ₁AM levels depend upon thyroid status and decrease upon induction of hypothyroidism. However, in hypothyroid mice replaced with H-T₄, the isotope-labeled H-T₃ metabolite is detected, but no isotope-labeled T₁AM is detected. These data suggest that T₁AM is not an extrathyroidal metabolite of T₄, yet is produced by a process that requires the same biosynthetic factors necessary for T₄ synthesis.