ObjectiveProlonged critically ill patients have low circulating thyroid hormone (TH) levels without a rise in TSH, a condition labeled ‘the low tri-iodothyronine (T₃) syndrome’. Currently, it is not clear whether this represents an adaptive response. We examined the role of TH transporters monocarboxylate transporter 8 (MCT8, also known as SLC16A2) and MCT10 in the pathogenesis of the low T₃ syndrome in prolonged critical illness.MethodsA clinical observational study in critically ill patients and an intervention study in an in vivo animal model of critical illness. Gene expression levels of MCT8 and MCT10 were measured by real-time PCR.ResultsIn prolonged critically ill patients, we measured increased MCT8 but not MCT10 gene expression levels in liver and skeletal muscle as compared with patients undergoing acute surgical stress. In a rabbit model of prolonged critical illness, gene expression levels of MCT8 in liver and of MCT10 in skeletal muscle were increased as compared with healthy controls. Treatment of prolonged critically ill rabbits with TH (thyroxine+T₃) resulted in a downregulation of gene expression levels of MCT8 in liver and of MCT10 in muscle. Transporter expression levels correlated inversely with circulating TH parameters.ConclusionsThese data suggest that alterations in the expression of TH transporters do not play a major role in the pathogenesis of the ‘low T₃ syndrome’ but rather reflect a compensatory effort in response to hypothyroidism.