Changes in metabolism of TRH in euthyroid sick syndrome. (1/47)

OBJECTIVE: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 microg, in patients with euthyroid sick syndrome (ESS). PATIENTS AND METHODS: A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30min after TRH injection. We analyzed the volume of distribution (V(d)), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t(1/2)) and the TSH response to the injection of TRH. RESULTS: All patients had lower tri-iodothyronine (T(3)) levels compared with controls (0.9 +/- 0. 1nmol/l vs 1.9 +/- 0.1 nmol/l; P < 0.0001; mean +/- S.D.; paired t-test). In addition, the V(d) (16.7 +/- 5.9/l vs 30.6 +/- 0.6/l; P < 0.0005) and PCR (2.0 +/- 0.80 l/min vs 3.3 +/- 0.25 l/min; P <0. 0005) were found statistically lowered in patients than in controls, whereas FCR (0.119 +/- 0.01 permin vs 0.110 +/- 0.01 per min; P < 0. 025) was found increased in patients as opposed to controls. The t(1/2) of exogenously administered TRH was increased in ESS compared with controls (7.2 +/- 0.7 min vs 6.3 +/- 0.6 min; P <0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. CONCLUSIONS: The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome.  (+info)

Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction. (2/47)

OBJECTIVE: In patients with acute myocardial infarction (AMI), low triiodothyronine (T(3)) levels with normal or subnormal levels of thyrotropin (TSH), the euthyroid sick syndrome (ESS), have been reported, however, the mechanism of altered thyroid hormone metabolism is unknown. Recent reports have shown that interleukin-6 (IL-6) plays a key role in the pathogenesis of AMI and ESS. This preliminary study investigates the relationship between thyroid states and plasma levels of IL-6, the soluble IL-6 receptor (sIL-6R), and the soluble transducing 130kDa glycoprotein (sgp130) in AMI. DESIGN AND METHODS: We measured the concentration of TSH, free T(3) (FT(3)), free thyroxine (FT(4)), IL-6, sIL-6R and sgp130 in plasma from 24 patients with AMI and 20 normal controls. RESULTS: All 24 AMI patients showed significantly lower concentrations of FT(3) with normal or subnormal levels of TSH, and higher concentrations of IL-6 and sIL-6R than controls. IL-6 level was correlated with creatine phosphokinase (CPK) and FT(3) levels but not with FT(4 )or TSH levels in patients with AMI. The time course of IL-6 and FT(3 )concentration seemed to be closely linked. sIL-6R level was correlated with CPK and sgp130 levels, but not with FT(3), FT(4) or TSH levels. FT(4 )level was correlated with sgp130 level. CONCLUSION: Patients with AMI develop ESS through activation of IL-6 and its receptor system.  (+info)

A potential role of activated NF-kappa B in the pathogenesis of euthyroid sick syndrome. (3/47)

Euthyroid sick syndrome, characterized by low serum 3,5, 3'-triiodothyronine (T(3)) with normal L-thyroxine levels, is associated with a wide variety of disorders including sepsis, malignancy, and AIDS. The degree of low T(3) in circulation has been shown to correlate with the severity of the underlying disorders and with the prognosis. Elevated TNF-alpha levels, which accompany severe illness, are associated with decreased activity of type I 5'-deiodinase (5'-DI) in liver, leading us to speculate that high levels of this factor contribute to euthyroid sick syndrome. Here we demonstrate that the activation of NF-kappa B by TNF-alpha interferes with thyroid-hormone action as demonstrated by impairment of T(3)-dependent induction of 5'-DI gene expression in HepG2 cells. Inhibition of NF-kappa B action by a dominant-negative NF-kappa B reversed this effect and allowed T(3) induction of 5'-DI. Furthermore, we show that an inhibitor of NF-kappa B activation, clarithromycin (CAM), can inhibit TNF-alpha-induced activation of NF-kappa B and restore T(3)-dependent induction of 5'-DI mRNA and enzyme activity. These results suggest that NF-kappa B activation by TNF-alpha is involved in the pathogenesis of euthyroid sick syndrome and that CAM could help prevent a decrease in serum T(3) levels and thus ameliorate euthyroid sick syndrome.  (+info)

Regulation of hepatocyte thyroxine 5'-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome. (4/47)

The syndrome of nonthyroidal illness, also known as the sick euthyroid syndrome, is characterized by a low plasma T3 and an "inappropriately normal" plasma thyrotropin in the absence of intrinsic disease of the hypothalamic-pituitary-thyroid axis. The syndrome is due in part to decreased activity of type I iodothyronine 5'-deiodinase (5' D-I), the hepatic enzyme that converts thyroxine to T3 and that is induced at the transcriptional level by T3. The hypothesis tested is that cytokines decrease T3 induction of 5' D-I, resulting in decreased T3 production and hence a further decrease in 5' D-I. The proposed mechanism is competition for limiting amounts of nuclear receptor coactivators between the 5' D-I promoter and the promoters of cytokine-induced genes. Using primary cultures of rat hepatocytes, we demonstrate that interleukins 1 and 6 inhibit the T3 induction of 5' D-I RNA and enzyme activity. This effect is at the level of transcription and can be partially overcome by exogenous steroid receptor coactivator-1 (SRC-1). The physical mass of endogenous SRC-1 is not affected by cytokine exposure, and exogenous SRC-1 does not affect 5' D-I in the absence of cytokines. The data support the hypothesis that cytokine-induced competition for limiting amounts of coactivators decreases hepatic 5' D-I expression, contributing to the etiology of the sick euthyroid syndrome.  (+info)

Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak. (5/47)

Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore generated mice carrying a null mutation in iyk, the mouse homolog of Frk/rak. We report here that frk/rak(-/-) mice are viable, show similar growth rates to wild-type animals, and are fertile. Furthermore, a 2-year study of health and survival did not identify differences in the incidence and spectrum of spontaneous tumors or provide evidence of hyperplasias in frk/rak(-/-) epithelial tissues. Histological analysis of organs failed to reveal any morphological changes in epithelial tissues that normally express high levels of Frk/rak. Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation. Additionally, frk/rak-null mice do not display altered sensitivity to intestinal damage induced by ionizing radiation. cDNA microarray analysis revealed an increase in c-src expression and identified subtle changes in the expression of genes regulated by thyroid hormones. Significant decreases in the circulating levels of T3 but not T4 hormone are consistent with this observation and reminiscent of euthyroid sick syndrome, a stress-associated clinical condition.  (+info)

Sick euthyroid syndrome is associated with decreased TR expression and DNA binding in mouse liver. (6/47)

Infection is associated with low serum thyroid hormones and thyrotropin levels. Here we demonstrate that infection also reduces thyroid hormone receptor (TR) expression. In gel shift experiments, retinoid X receptor (RXR)/TR DNA binding was reduced in mouse liver by 60 and 77%, respectively, 4 and 16 h after lipopolysaccharide (LPS) administration. Surprisingly, LPS did not decrease either TR-alpha or TR-beta protein levels at 4 h, but by 16 h TR-alpha(1), TR-alpha(2), and TR-beta levels were reduced by 55, 87, and 41%, respectively. We previously reported that LPS rapidly decreases RXR protein levels in liver. Therefore, we added RXR-beta to hepatic nuclear extracts prepared 4 h after LPS treatment, which restored RXR/TR DNA binding to a level comparable to that of controls. A similar experiment conducted on extracts prepared 16 h after LPS administration did not restore RXR/TR DNA binding. We propose that decreased RXR expression is limiting for RXR/TR DNA binding at 4 h, whereas the reduction in both TR and RXR levels results in further decreased binding at 16 h.  (+info)

Circulating IL-8 and IL-10 in euthyroid sick syndromes following bone marrow transplantation. (7/47)

It is generally agreed that euthyroid sick syndromes (ESS) are associated with an increased production of cytokines. However, there has been scarce data on the relationship thyroid hormone changes and cytokines among the patients undergoing bone marrow transplantation (BMT). Because interleukin-8 (IL-8) has been identified as a potent proinflammatory and interleukin-10 (IL-10) as an antiinflammatory cytokine, we studied the relation between thyroid hormone parameters and these cytokines following BMT. We studied 80 patients undergoing allogeneic BMT. Serum T3 decreased to nadir at post-BMT 3 weeks. Serum T4 was the lowest at the post-BMT 3 months. Serum TSH sharply decreased to nadir at 1 week and gradually recovered. Serum free T4 significantly increased during 3 weeks and then returned to basal level. Mean levels of serum IL-8 significantly increased at 1 week after BMT. Mean levels of serum IL-10 significantly increased until 4 weeks after BMT. No significant correlation was found between serum thyroid hormone parameters and cytokines (IL-8, IL-10) after adjusting steroid doses during the entire study period. In conclusion, ESS developed frequently following allogeneic BMT and cytokine levels were increased in post-BMT patients. However, no significant correlation was found between serum thyroid hormone parameters and these cytokines.  (+info)

Effects of moderate to severe osteoarthritis on canine thyroid function. (8/47)

Several nonthyroidal illnesses in euthyroid dogs can affect the results of thyroid function testing, making interpretation of the results more difficult with an increased risk of overdiagnosing hypothyroidism. The purpose of this study was to evaluate the effect of chronic, moderate to severe, osteoarthritis on canine thyroid function. Ninety-six, healthy, client-owned dogs, 65 of which were suffering from moderate to severe osteoarthritis and 31 euthyroid dogs without any physical evidence of osteoarthritis, were used in this study. Blood samples were collected to evaluate serum basal total thyroxine (TT4), free thyroxine (FT4), and thyrotropin (TSHc) concentrations. Basal serum TT4 concentration was not affected by osteoarthritis in dogs. Mild, but statistically significant, differences were noticed in FT4 and TSHc concentrations among the 2 groups. However, this had limited clinical relevance, since virtually all values were within their reference range, and no dogs would have been misdiagnosed as hypothyroid. Therefore, based on the results of our study, osteoarthritis does not need to be considered a factor influencing thyroid function evaluation in dogs.  (+info)

• 1
• 2
• 3
• 4
• 5
• 6