title: Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay.
abstract: BACKGROUND
  Thyronamines are thyronergic metabolites of thyroid hormones. Lack of reliable and sensitive detection methods for endogenous 3-iodothyronamine (3-T(1)AM) 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(1)AM antibodies and established a monoclonal antibody-based chemiluminescence immunoassay as a powerful tool for monitoring 3-T(1)AM levels in investigations addressing altered serum profiles and potential sites of origin and action of 3-T(1)AM in humans.
  
  
  METHODS
  Our exploratory study on 3-T(1)AM serum levels in humans measured 3-T(1)AM concentrations in comparison with thyroid hormones.
  
  
  METHODS
  Thirteen adult healthy subjects, 10 patients with pituitary insufficiency, and 105 thyroid cancer patients participated.
  
  
  METHODS
  INTERVENTIONS included l-T(4) withdrawal in patients with pituitary insufficiency as well as TSH-suppressive T(4) substitution in thyroid cancer patients.
  
  
  RESULTS
  3-T(1)AM 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-T(1)AM was also detected in T(4)-substituted thyroid cancer patients. Although free T(4) and T(3) significantly decreased during T(4) withdrawal, 3-T(1)AM levels remained constant for 6 d.
  
  
  CONCLUSIONS
  Because higher 3-T(1)AM levels are detectable in T(4)-substituted thyroid cancer patients after thyroidectomy/radioiodine treatment compared with healthy controls, we concluded that 3-T(1)AM is mainly produced by extrathyroidal tissues. The serum profile during T(4) withdrawal suggests either a long half-life or persisting 3-T(1)AM release into serum from intracellular thyroid hormone precursors or stores.
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Carolin S
authors.initials: CS
authors.lastname: Hoefig
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.forename: Kashinath
authors.initials: K
authors.lastname: Dixit
authors.forename: Beng
authors.initials: B
authors.lastname: Yap
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.forename: Zida
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007018:Hypopituitarism / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D013963:Thyroid Hormones / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013970:Thyronines / Q000096:biosynthesis* / Q000097:blood
chemical_list: C487948:3-iodothyronamine; D000911:Antibodies, Monoclonal; D013963:Thyroid Hormones; D013970:Thyronines