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

Anastasiou O, Sydor S, Sowa JP, Manka P, Katsounas A, Syn WK, Führer D, Gieseler RK, Bechmann LP, Gerken G, Moeller LC, Canbay A - PLoS ONE (2015)

Bottom Line: These patients had greater risk for an adverse outcome than euthyroid patients.SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients.Albumin concentrations were significantly higher in SR than in NSR.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg, Essen, 45122, Essen, Germany.

ABSTRACT

Introduction: Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.

Methods: 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined.

Results: More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.

Conclusions: In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

No MeSH data available.


Related in: MedlinePlus

Gene expression in primary human hepatocytes after toxic injury and T3 stimulation.mRNA expressions of cell death related genes CD95 (A) and NOXA (B), as well as the thyroid hormone receptor β1 (THR B, C) and hepatocyte growth facor (HGF, D) were assessed. APAP significantly reduced mRNA expressions of CD95 (Fas receptor), THR B, and HGF. * p < 0.05 compared to vehicle (ethanol); # p < 0.05 compared to T3. Statistical significance experiments was determined by one-way ANOVA with Tukey’s post-hoc test for individual experimental conditions. APAP: acetaminophen; CH11: CD95/FAS-agonist to induce apoptosis; T3: triiodothyronine.
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pone.0132189.g004: Gene expression in primary human hepatocytes after toxic injury and T3 stimulation.mRNA expressions of cell death related genes CD95 (A) and NOXA (B), as well as the thyroid hormone receptor β1 (THR B, C) and hepatocyte growth facor (HGF, D) were assessed. APAP significantly reduced mRNA expressions of CD95 (Fas receptor), THR B, and HGF. * p < 0.05 compared to vehicle (ethanol); # p < 0.05 compared to T3. Statistical significance experiments was determined by one-way ANOVA with Tukey’s post-hoc test for individual experimental conditions. APAP: acetaminophen; CH11: CD95/FAS-agonist to induce apoptosis; T3: triiodothyronine.

Mentions: To investigate if T3 may be able to diminish cellular injury PHH isolated from 3 different donors were treated with acetaminophen (APAP) or CH11 to induce necrotic or apoptotic cell death, respectively. T3 treatment was performed in parallel to the cell injury, to mimic the condition of ALF, where cell death is already established upon diagnosis. Activation of thyroid hormone receptor signaling by T3 was checked by mRNA expression of deiodinase 1 (DIO1). T3 stimulation resulted in significant upregulation of DIO1 mRNA (see S3 Fig). APAP or CH11 treatment did not lead to macroscopically observable cell death in PHH. Though, CH11 treatment led to an increase of M30 (a caspase-cleaved cytokeratin18 fragment; data not shown). Expression of the Fas receptor CD95 was significantly reduced in APAP treated cells compared to vehicle, irrespective of T3 stimulation (Fig 4A). NOXA mRNA, serving as an early marker of apoptosis, was not affected by any treatment condition (Fig 4B). Similar to CD95 mRNA, expression of the thyroid hormone receptor β1 (THR B, Fig 4C) and of hepatocyte growth factor (HGF, Fig 4D) were significantly diminished by APAP compared to vehicle. In summary T3 stimulation did not affect APAP induced reduction of cell death related or growth factor mRNA expression.


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

Anastasiou O, Sydor S, Sowa JP, Manka P, Katsounas A, Syn WK, Führer D, Gieseler RK, Bechmann LP, Gerken G, Moeller LC, Canbay A - PLoS ONE (2015)

Gene expression in primary human hepatocytes after toxic injury and T3 stimulation.mRNA expressions of cell death related genes CD95 (A) and NOXA (B), as well as the thyroid hormone receptor β1 (THR B, C) and hepatocyte growth facor (HGF, D) were assessed. APAP significantly reduced mRNA expressions of CD95 (Fas receptor), THR B, and HGF. * p < 0.05 compared to vehicle (ethanol); # p < 0.05 compared to T3. Statistical significance experiments was determined by one-way ANOVA with Tukey’s post-hoc test for individual experimental conditions. APAP: acetaminophen; CH11: CD95/FAS-agonist to induce apoptosis; T3: triiodothyronine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493082&req=5

pone.0132189.g004: Gene expression in primary human hepatocytes after toxic injury and T3 stimulation.mRNA expressions of cell death related genes CD95 (A) and NOXA (B), as well as the thyroid hormone receptor β1 (THR B, C) and hepatocyte growth facor (HGF, D) were assessed. APAP significantly reduced mRNA expressions of CD95 (Fas receptor), THR B, and HGF. * p < 0.05 compared to vehicle (ethanol); # p < 0.05 compared to T3. Statistical significance experiments was determined by one-way ANOVA with Tukey’s post-hoc test for individual experimental conditions. APAP: acetaminophen; CH11: CD95/FAS-agonist to induce apoptosis; T3: triiodothyronine.
Mentions: To investigate if T3 may be able to diminish cellular injury PHH isolated from 3 different donors were treated with acetaminophen (APAP) or CH11 to induce necrotic or apoptotic cell death, respectively. T3 treatment was performed in parallel to the cell injury, to mimic the condition of ALF, where cell death is already established upon diagnosis. Activation of thyroid hormone receptor signaling by T3 was checked by mRNA expression of deiodinase 1 (DIO1). T3 stimulation resulted in significant upregulation of DIO1 mRNA (see S3 Fig). APAP or CH11 treatment did not lead to macroscopically observable cell death in PHH. Though, CH11 treatment led to an increase of M30 (a caspase-cleaved cytokeratin18 fragment; data not shown). Expression of the Fas receptor CD95 was significantly reduced in APAP treated cells compared to vehicle, irrespective of T3 stimulation (Fig 4A). NOXA mRNA, serving as an early marker of apoptosis, was not affected by any treatment condition (Fig 4B). Similar to CD95 mRNA, expression of the thyroid hormone receptor β1 (THR B, Fig 4C) and of hepatocyte growth factor (HGF, Fig 4D) were significantly diminished by APAP compared to vehicle. In summary T3 stimulation did not affect APAP induced reduction of cell death related or growth factor mRNA expression.

Bottom Line: These patients had greater risk for an adverse outcome than euthyroid patients.SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients.Albumin concentrations were significantly higher in SR than in NSR.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg, Essen, 45122, Essen, Germany.

ABSTRACT

Introduction: Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.

Methods: 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined.

Results: More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.

Conclusions: In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

No MeSH data available.


Related in: MedlinePlus