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Tissue Deiodinase Activity during Prolonged Critical Illness: Effects of Exogenous Thyrotropin-Releasing Hormone and Its Combination with Growth Hormone-Releasing Peptide-2

Department of Intensive Care Medicine (Y.D., B.E., L.M., G.V.d.B.), Laboratory for Experimental Medicine and Endocrinology (E.V.H., W.C.), and Laboratory of Comparative Endocrinology (V.D.), Catholic University of Leuven, B-3000 Leuven, Belgium; and Department of Anesthesiology and Intensive Care Medicine, University Hospital of Muenster (B.E.), D-48149 Muenster, Germany

Address all correspondence and requests for reprints to: Dr. Greet Van den Berghe, Department of Intensive Care Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium. E-mail: greta.vandenberghe{at}med.kuleuven.be.

Prolonged critical illness is characterized by reduced pulsatile TSH secretion, causing reduced thyroid hormone release and profound changes in thyroid hormone metabolism, resulting in low circulating T₃ and elevated rT₃ levels. To further unravel the underlying mechanisms, we investigated the effects of exogenous TRH and GH-releasing peptide-2 (GHRP-2) in an in vivo model of prolonged critical illness. Burn-injured, parenterally fed rabbits were randomized to receive 4-d treatment with saline, 60 µg/kg·h GHRP-2, 60 µg/kg·h TRH, or 60 µg/kg·h TRH plus 60 µg/kg·h GHRP-2 started on d 4 of the illness (n = 8/group). The activities of the deiodinase 1 (D1), D2, and D3 in snap-frozen liver, kidney, and muscle as well as their impact on circulating thyroid hormone levels were studied. Compared with healthy controls, hepatic D1 activity in the saline-treated, ill animals was significantly down-regulated (P = 0.02), and D3 activity tended to be up-regulated (P = 0.06). Infusion of TRH and TRH plus GHRP-2 restored the catalytic activity of D1 (P = 0.02) and increased T₃ levels back within physiological range (P = 0.008). D3 activity was normalized by all three interventions, but only addition of GHRP-2 to TRH prevented the rise in rT₃ seen with TRH alone (P = 0.02). Liver D1 and D3 activity were correlated (respectively, positively and negatively) with the changes in circulating T₃ (r = 0.84 and r = –0.65) and the T₃/rT₃ ratio (r = 0.71 and r = –0.60). We conclude that D1 activity during critical illness is suppressed and related to the alterations within the thyrotropic axis, whereas D3 activity tends to be increased and under the joint control of the somatotropic and thyrotropic axes.

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				Y. Debaveye, B. Ellger, L. Mebis, T. J. Visser, V. M. Darras, and G. Van den Berghe Effects of Substitution and High-Dose Thyroid Hormone Therapy on Deiodination, Sulfoconjugation, and Tissue Thyroid Hormone Levels in Prolonged Critically Ill Rabbits Endocrinology, August 1, 2008; 149(8): 4218 - 4228. [Abstract] [Full Text] [PDF]