Evidence for Extrathyroidal Formation of 3-Iodothyronamine in Humans as Provided by a Novel Monoclonal Antibody-Based Chemiluminescent Serum Immunoassay

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 6; pp. 1864 - 1872
• Main Authors: Hoefig, Carolin S., Köhrle, Josef, Brabant, Georg, Dixit, Kashinath, Yap, Beng, Strasburger, Christian J., Wu, Zida
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.06.2011
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Chemiluminescence; Enzyme-Linked Immunosorbent Assay; Female; Homeostasis; Hormones; Humans; Hypopituitarism - metabolism; Immunoassay; Luminescent Measurements; Male; Middle Aged; Monoclonal antibodies; Pituitary; Serum levels; Thyroid cancer; Thyroid hormones; Thyroid Hormones - metabolism; Thyroid Neoplasms - metabolism; Thyroid-stimulating hormone; Thyroidectomy; Thyronines - biosynthesis; Thyronines - blood; Thyroxine; Triiodothyronine
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2010-2680

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-T1AM antibodies and established a monoclonal antibody-based chemiluminescence immunoassay as a powerful tool for monitoring 3-T1AM 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 T4 withdrawal, 3-T1AM levels remained constant for 6 d.Conclusion:Because higher 3-T1AM levels are detectable in T4-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 T4 withdrawal suggests either a long half-life or persisting 3-T1AM release into serum from intracellular thyroid hormone precursors or stores.