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

Carolin S. Hoefig; Josef Köhrle; Georg Brabant; Kashinath Dixit; Beng Yap; Christian J. Strasburger; Zida Wu

doi:10.1210/jc.2010-2680

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

Carolin S. Hoefig, Josef Köhrle^*, Georg Brabant, Kashinath Dixit, Beng Yap, Christian J. Strasburger, Zida Wu

^*Corresponding author for this work

Department of Internal Medicine I

75 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	96
Issue number	6
Pages (from-to)	1864-1872
Number of pages	9
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2010-2680
Publication status	Published - 01.06.2011

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10.1210/jc.2010-2680

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@article{7c325998ccfe4f87926b735ce598d283,

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

abstract = "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.",

author = "Hoefig, \{Carolin S.\} and Josef K{\"o}hrle and Georg Brabant and Kashinath Dixit and Beng Yap and Strasburger, \{Christian J.\} and Zida Wu",

year = "2011",

month = jun,

day = "1",

doi = "10.1210/jc.2010-2680",

language = "English",

volume = "96",

pages = "1864--1872",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

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Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay. / Hoefig, Carolin S.; Köhrle, Josef; Brabant, Georg et al.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 6, 01.06.2011, p. 1864-1872.

Research output: Journal Articles › Journal articles › Research › peer-review

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 - https://www.scopus.com/pages/publications/79956319556

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 -

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

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