Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay

Context: Thyronamines are thyronergic metabolites of thyroid hormones. Lack of reliable and sensitive detection methods for endogenous 3-iodothyronamine (3-T₁AM) has so far hampered progress in understanding their physiological action and role in endocrine homeostasis or pathophysiology of diseases. Objective: We characterized newly generated mouse monoclonal 3-T ₁AM antibodies and established a monoclonal antibody-based chemiluminescence immunoassay as a powerful tool for monitoring 3-T ₁AM levels in investigations addressing altered serum profiles and potential sites of origin and action of 3-T₁AM in humans. Design and Setting: Our exploratory study on 3-T₁AM serum levels in humans measured 3-T₁AM concentrations in comparison with thyroid hormones. Patients or Other Participants: Thirteen adult healthy subjects, 10 patients with pituitary insufficiency, and 105 thyroid cancer patients participated. Interventions: Interventions included L-T₄ withdrawal in patients with pituitary insufficiency as well as TSH-suppressive T₄ substitution in thyroid cancer patients. Results: 3-T₁AM was reliably quantified in human serum and stable after storage at room temperature and 4 C overnight as well as after four freeze-thaw cycles. The median serum concentration in healthy subjects was 66 ± 26 nM. 3-T₁AM was also detected in T₄-substituted thyroid cancer patients. Although free T₄ and T₃ significantly decreased during T ₄ withdrawal, 3-T₁AM levels remained constant for 6 d. Conclusion: Because higher 3-T₁AM levels are detectable in T ₄-substituted thyroid cancer patients after thyroidectomy/radioiodine treatment compared with healthy controls, we concluded that 3-T₁AM is mainly produced by extrathyroidal tissues. The serum profile during T ₄ withdrawal suggests either a long half-life or persisting 3-T ₁AM release into serum from intracellular thyroid hormone precursors or stores.