TY - JOUR
T1 - Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay
AU - Hoefig, Carolin S.
AU - Köhrle, Josef
AU - Brabant, Georg
AU - Dixit, Kashinath
AU - Yap, Beng
AU - Strasburger, Christian J.
AU - Wu, Zida
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79956319556&partnerID=8YFLogxK
U2 - 10.1210/jc.2010-2680
DO - 10.1210/jc.2010-2680
M3 - Journal articles
C2 - 21490071
AN - SCOPUS:79956319556
SN - 0021-972X
VL - 96
SP - 1864
EP - 1872
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -
