Expression of thyroid hormone transporters during critical illness.
OBJECTIVE
Prolonged critically ill patients have low circulating thyroid hormone (TH) levels without a rise in TSH, a condition labeled 'the low tri-iodothyronine (T(3)) 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 T(3) syndrome in prolonged critical illness.


METHODS
A 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.


RESULTS
In 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+T(3)) 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.


CONCLUSIONS
These data suggest that alterations in the expression of TH transporters do not play a major role in the pathogenesis of the 'low T(3) syndrome' but rather reflect a compensatory effort in response to hypothyroidism.
Mebis
Liese
L
Department of Intensive Care Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Paletta
Deborah
D
Debaveye
Yves
Y
Ellger
Björn
B
Langouche
Lies
L
D'Hoore
André
A
Darras
Veerle M
VM
Visser
Theo J
TJ
Van den Berghe
Greet
G
D000368:Aged; D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D016638:Critical Illness; D004195:Disease Models, Animal; D005067:Euthyroid Sick Syndromes / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency; D014285:Triiodothyronine, Reverse / Q000097:blood
D026921:Amino Acid Transport Systems, Neutral; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013974:Thyroxine