Evidence for Extrathyroidal Formation of 3-Iodothyronamine in Humans as Provided by a Novel Monoclonal Antibody-Based Chemiluminescent Serum Immunoassay
Evidence for Extrathyroidal Formation of 3-Iodothyronamine in Humans as Provided by a Novel Monoclonal Antibody-Based Chemiluminescent Serum Immunoassay
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DOI：
10.1210/jc.2010-2680
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发表时间：
2011-06-01
影响因子：
5.8
通讯作者：
Wu, Zida
中科院分区：
文献类型：
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作者：
Hoefig, Carolin S.;Koehrle, Josef;Wu, Zida
背景：甲状腺胺是甲状腺激素的甲状腺能代谢产物。到目前为止，内源性3 - 碘甲状腺胺（3 - T(1)AM）缺乏可靠且灵敏的检测方法，阻碍了对其生理作用以及在内分泌稳态或疾病病理生理学中作用的理解进展。
目的：我们对新产生的小鼠单克隆3 - T(1)AM抗体进行了特性分析，并建立了一种基于单克隆抗体的化学发光免疫分析法，作为在研究人类血清特征改变以及3 - T(1)AM的潜在起源部位和作用时监测3 - T(1)AM水平的有力工具。
设计与环境：我们对人类3 - T(1)AM血清水平的探索性研究测量了3 - T(1)AM浓度，并与甲状腺激素进行了比较。
患者或其他参与者：13名成年健康受试者、10名垂体功能不全患者和105名甲状腺癌患者参与了研究。
干预措施：干预措施包括垂体功能不全患者停用L - T(4)以及甲状腺癌患者进行抑制促甲状腺激素（TSH）的T(4)替代治疗。
结果：3 - T(1)AM在人血清中能够可靠地定量，在室温及4℃过夜储存以及经过4次冻融循环后仍保持稳定。健康受试者的血清中位浓度为66 ± 26 nM。在接受T(4)替代治疗的甲状腺癌患者中也检测到了3 - T(1)AM。尽管在停用T(4)期间游离T(4)和T(3)显著降低，但3 - T(1)AM水平在6天内保持恒定。
结论：由于甲状腺切除/放射性碘治疗后接受T(4)替代治疗的甲状腺癌患者与健康对照相比可检测到更高的3 - T(1)AM水平，我们得出结论：3 - T(1)AM主要由甲状腺外组织产生。停用T(4)期间的血清特征表明，要么其半衰期较长，要么3 - T(1)AM从细胞内甲状腺激素前体或储存库持续释放到血清中。（《临床内分泌与代谢杂志》96: 1864 - 1872, 2011）
Context: 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.Design and Setting: Our exploratory study on 3-T(1)AM serum levels in humans measured 3-T(1)AM 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-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.Conclusion: 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. (J Clin Endocrinol Metab 96: 1864-1872, 2011)