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Cited by 23Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersHormonal and reproductive studies

Circulating 3-T1AM and 3,5-T2 in critically ill patients: a cross-sectional observational study

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Langouche, Lies, Lehmphul, Ina, Perre, Sarah Vander, Köhrle, Josef, Van den Berghe, Greet·2016·Thyroid®
DOI 10.1089/thy.2016.0214
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Abstract

Background: Critical illness is hallmarked by low circulating thyroxine (T4) and triiodothyronine (T3) concentrations, in the presence of elevated reverse T3 (rT3) and low-normal thyrotropin (TSH), referred to as nonthyroidal illness (NTI). Thyroid hormone (TH) metabolism is substantially increased during NTI, in part explained by enhanced deiodinase 3 (D3) activity. T4- and T3-sulfate concentrations are elevated, due to suppressed D1 activity in the presence of unaltered sulfotransferase activity, and 3,3′-diiodothyronine (3,3′-T2) concentrations are normal. To elucidate further the driving forces behind increased TH metabolism during NTI, two other potential T4 metabolites—3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM)—were measured and related to their potential TH precursors. Methods: Morning blood samples were collected cross-sectionally from 83 critically ill patients on a University Hospital intensive care unit and from 38 demographically matched healthy volunteers. Serum TH and binding proteins were quantified with commercial assays, and 3,5-T2 and 3-T1AM with in-house developed immunoassays. Results: Critically ill patients revealed, besides the NTI, a median 44% lower serum 3-T1AM concentration ( p < 0.0001) and a 30% higher serum 3,5-T2 concentration ( p = 0.01) than healthy volunteers did. Non-survivors and patients diagnosed with sepsis upon admission to the intensive-care unit had significantly higher 3,5-T2 ( p ≤ 0.01) but comparable 3-T1AM ( p > 0.2) concentrations than other patients did. Multivariable linear regression analysis adjusted for potential precursors revealed that the reduced serum 3-T1AM was positively correlated with the low serum T3 ( p < 0.001) but unrelated to serum T4 or rT3. The elevated 3,5-T2 concentration did not independently correlate with TH. Conclusions: Increased TH metabolism during NTI could not be explained by increased conversion to 3-T1AM, as circulating 3-T1AM was suppressed in proportion to the concomitantly low T3 concentrations. Increased conversion of T4 and/or T3 to 3,5-T2 could be possible, as serum 3,5-T2 concentrations were elevated. Whether 3-T1AM or 3,5-T2 plays a functional role during critical illness needs further investigation.

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  • In a group of intensive care unit (ICU) patients, non-survivors had significantly higher 3,5-T2 concentrations than those who survived.

    “Of interest was the observation that, in a group of intensive care unit (ICU) patients, non-survivors had significantly higher 3,5-T2 concentrations than those who survived (42).”

    From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [42]

    The Results section (“Circulating thyroid hormones, metabolites and binding proteins”; page not given) reports higher serum 3,5-T2 in ICU non-survivors than survivors. It does not explicitly establish statistical significance for that comparison; its explicit significance statement concerns ICU patients versus healthy controls. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Langouche, L., Lehmphul, I., Perre, S. V., Köhrle, J., & Van den Berghe, G.
Affiliations
  • KU Leuven (BE)
  • Charité – Universitätsmedizin Berlin (DE)
  • KU Leuven
Corresponding author
Langouche, Lies
ORCID
Venue
Thyroid®
Publisher
SAGE Publications
Published
2016-12
Volume
26
Issue
12
Pages
1674-1680
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2016.0214
OpenAlex
W2395950874
Cited by
23
References
6
Citations by year
2025: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 1
FWCI
4.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Thyroid (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
Funders
  • European Commission
  • Deutsche Forschungsgemeinschaft (922/17-1, KO 922/16-2)
  • KU Leuven
  • Vlaamse regering (METH/08/07, METH/14/06)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
3,5-diiodothyronine, low T3 syndrome, critical illness, thyroid hormone metabolism, triiodothyronine, thyroxine, reverse T3, sepsis, critically ill patients, thyroid-binding proteins
MeSH terms
Aged, Cross-Sectional Studies, Diiodothyronines, Female, Humans, Intensive Care Units, Male, Middle Aged, Thyroid Function Tests, Thyronines, Critical Illness

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