Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study.
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.



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.



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.



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.
1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium .
Lies
L
Langouche
2 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
Ina
I
Lehmphul
1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium .
Sarah Vander
SV
Perre
2 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany .
Josef
J
Köhrle
1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium .
Greet
G
Van den Berghe
D000368:Aged; D016638:Critical Illness; D003430:Cross-Sectional Studies; D004104:Diiodothyronines / Q000097:blood*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D013960:Thyroid Function Tests; D013970:Thyronines / Q000097:blood*
C487948:3-iodothyronamine; D004104:Diiodothyronines; D013970:Thyronines; C030103:3,5-diiodothyronine
NTI; critical illness; metabolites; sepsis; thyroid hormones