Introduction: Patients in need of an intensive care unit (ICU) treatment due to severe diseases often develop the non-thyroidal illness syndrome (NTI). These critically ill patients present with low thyroxine (T4), low 3,3,5-triiodothyronine (T3) and elevated reverse T3 (rT3) serum concentrations while TSH and 3,3-diiodothyronine (3,3-T2) concentrations remain unaffected. To further elucidate the underlying changes in thyroid hormone (TH) metabolism, additional TH metabolites of physiological and pathophysiological relevance were determined in sera of ICU patients.
Study design: In this cross-sectional observational study blood was drawn from 83 ICU patients who were followed up during their ICU stay. 25 developed sepsis and 10 patients did not survive ICU stay. The control group consists of 38 healthy and demographically matched individuals.
Methods: TH and their binding proteins were measured with commercial assays. 3,5-T2 and 3-T1AM were determined with published in-house immunoassays.
Results: Classical TH function tests documented a NTI constellation. Median 3-T1AM concentrations were 44% lower throughout the ICU stay compared to the healthy control (P<0.0001). 3-T1AM is not different in survivors vs. non-survivors or sepsis vs. non-sepsis patients. Median 3,5-T2 concentrations were 30% higher in critically ill patients compared to the control group (P=0.01). In addition, we also observed that non-survivors and ICU patients with diagnosed sepsis had higher 3,5-T2 concentrations compared to other ICU patients. 3-T1AM but not 3,5-T2 correlates with low T3.
Conclusion: We found highest 3,5-T2 and low 3-T1AM values in most severely ill patients (non-survivors and sepsis patients). This data may indicate enhanced T3 deiodination to 3,5-T2 concomitant with decreased 3,5-T2 elimination. The observation that 3-T1AM concentration does not change with severity of illness or is even declining with decreasing T3, is compatible with our hypothesis that 3,5-T2 serves as substrate for a decarboxylase yielding 3-T1AM, whose activity is impaired in severe NTI on ICU.