Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences

Abstract

Thyroid hormones are now recognized to change in different disease states with important consequences on severity and prognosis of disease. However, little is known about thyroid hormones' alterations in acute liver failure (ALF). To study the changes in thyroid hormones and cardiac thyroid receptors during ALF, we subjected seven female pigs to surgical liver devascularization. Liver function biochemical markers, thyroid hormones, endogenous opioids, malondialdehyde (MDA), and interleukins 1 and 6 were measured in serum for 24 h postoperatively. Heart biopsies were harvested at the end of the experiment. Baseline heart biopsies were taken from five additional animals. Serum thyroxin (T(4)) and triiodothyronine (T(3)) levels markedly decreased, whereas free-triiodothyronine and thyroxin-stimulating hormone levels did not change. T(4) and T(3) levels correlated with the degree of liver failure and with MDA and interleukin-6 levels. Beta-endorphin levels initially increased, whereas levels of leucine-enkephalin did not change. Thyroid hormone receptor-alpha1 protein expression in the heart decreased 1.6-fold after ALF, whereas myocardial myosin isoform expression remained unchanged. The downregulation of T(4) and T(3) levels during ALF seems to correlate well with the severity of disease. This downregulation related to inflammation and oxidative stress and resulted in changes in myocardial thyroid receptors.

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

“…Although total hormone levels were changed significantly in the presented ALF cohort, free thyroid hormones did not differ between SR and NSR patients. This finding is in line with ALF in a pig model, where serum thyroxin T3 and T4 levels markedly decrease after ALF induction, whereas fT3 and fT4 levels did not change [ 19 ]. Reduction of total but not free hormone concentrations in NSR compared to SR patients might imply a deficit of transport proteins produced by the liver (i.e.…”

“…In a study of Kostopanagiotou et al . involving a pig model of ALF, serum T3 and T4 levels markedly decreased after induction of ALF, whereas fT3 and fT4 levels did not change [ 19 ]. In summary the above described data suggests that ALF leads to changes of thyroid serum parameters.…”

Low Free Triiodothyronine Levels are Related to Poor Prognosis in Acute Ischemic Stroke

“…The low T3 status as an independent predictor of death was also reported in patients with acute myocardial infarction ( Friberg et al, 2002 ), cardiac arrest ( Iltumur et al, 2005 ), heart failure ( Pingitore et al, 2005 ) and respiratory failure from pulmonary disorders ( Scoscia et al, 2004 ). Analogous fi ndings concerning thyroid hormone changes (with low T3 levels) in other diseases, like traumatic brain injury ( Cernak et al, 1999 ), acute liver failure ( Kostopanagiotou et al, 2009 ) and even chronic obstructive pulmonary disease ( Karadag et al, 2007 ), have been reported. Finally, low fT3 levels are associated with the increase of disease severity and higher mortality among critically ill patients, especially in intensive care units ( Chinga-Alayo et al, 2005 ).…”

Assessment of thyroid and gonadal function in liver diseases

“…This was due to decreased hepatic uptake and type-1 deiodinase activity (D1), which converts T4 to T3. [ 5 ] Liver disease is also associated with increase in inflammatory cytokines that negatively affect hypothalamothyroid axis,[ 11 21 ] which may explain lower TSH levels (statistically not significant) observed in patients with liver disease as compared to controls in this study. Other studies have reported higher levels of TSH in CLDs,[ 8 22 ] but these studies have not excluded patients with overt thyroid dysfunction, which we have excluded in this study before analysis.…”