triiodothyronine--reverse and Liver-Cirrhosis

The aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis.. The study group (Group A) comprised 31 patients (25 M, 6 F; median age 62.1 years, range 54.0-81.5 years) affected by HCV-related liver cirrhosis with superimposed HCC. Acute and chronic systemic disease, other than cirrhosis, inducing 'euthyroid sick syndrome' was excluded in all patients. Serum TSH, FT4, FT3, rT3, and thyroxine-binding globulin (TBG) levels were retrospectively evaluated in frozen aliquots drawn at the time of tumour diagnosis and every 6 months for 3-7 years before HCC diagnosis. The control group (Group B) comprised 29 patients affected by HCV-related liver cirrhosis without HCC, matched for sex, age and grade of liver dysfunction.. At the time of HCC diagnosis, all patients in Group A were euthyroid with serum TSH, FT4, FT3 and TBG values not significantly different from those of cirrhotic patients of Group B. However, at diagnosis Group A patients had serum rT3 values that were significantly higher than those in Group B (35.0 ng/dl, range 12.0-162.0 vs. 19.0 ng/dl, range 10.0-51.0; Group A vs. Group B; P < 0.001). Serum rT3 values above the normal range were found in 12 patients in Group A (38.7%) but in only one of the patients from Group B (3.4%) (chi2 10.2; P = 0.001). The serum rT3 levels were not significantly correlated to the Child grade of liver cirrhosis (rho 0.1; P = 0.5). The intrasubject analysis demonstrated that a significant increase in serum rT3 levels occurred at the time of HCC diagnosis but serum FT4, FT3 and TSH values did not change significantly. A receiver operating curve (ROC) demonstrated that a 6-monthly increase in serum rT3 levels of at least +22.5% identified patients with HCC with a diagnostic accuracy of 81.7%.. Our study has demonstrated that development of hepatocellular carcinoma is accompanied by a significant increase in serum rT3 levels in patients with low-grade HCV-related liver cirrhosis who had no other illness causing the 'euthyroid sick syndrome'.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Female; Hepacivirus; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Triiodothyronine, Reverse

Twenty-four-hour thyrotropin (TSH) profiles in eight severely ill patients were compared with those of six healthy subjects. The profiles were assessed using the cosinor method to evaluate circadian variations and using the Pulsar algorithm to analyze episodic secretion. In the normal subjects, the typical periodicity of TSH secretion showed a mean level in the rhythm (mesor) of 2.03 mU/l. The amplitude (half the extent of rhythmic change in the cycle) was 0.58 mU/l; the acrophase (the delay from midnight (0 degrees) of the highest level in the rhythm) was -9.9 degrees. In contrast, severely ill patients showed only slight and anticipated elevations of serum TSH levels (mesor 0.93 mU/l, amplitude 0.22 mU/l, acrophase +82.4 degrees). Moreover, whereas the episodic TSH secretion in healthy individuals consisted of 5-8 pulses/24 h, mainly clustered around midnight, only one pulse of reduced amplitude was detected in two of the eight severely ill patients and no pulses in the other six. Since earlier studies have indicated that the loss of TSH pulsatility is associated with the relative insensitivity of the thyrotrophs to low thyroid hormone levels and our analytical procedures have demonstrated that 24 h pulsatile pattern of TSH closely overlapped with baseline TSH secretion, it seems reasonable to assume that low-thyroid-hormone state, deficient pulsatile TSH secretion and altered nyctohemeral TSH periodicity do not coincide by chance, but that there is a causal relationship between such abnormalities in severely ill patients.

Topics: Adult; Circadian Rhythm; Female; Humans; Hypothyroidism; Liver Cirrhosis; Male; Middle Aged; Neoplasms; Pulsatile Flow; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Hepatic parenchymal tissue is known to be one of the major sites of thyroid hormone metabolism as well as glucagon action. Alterations in circulating thyroid hormone concentrations, as well as hyperglucagonemia, are well documented in subjects with hepatic cirrhosis and advanced liver dysfunction. Also, we have documented recently that hyperglucagonemia induced in normal subjects alters thyroid hormone metabolism, with lowering of serum T3 and a rise in serum reverse T3 (rT3) levels. Thus, it is conceivable that rising glucagon concentrations are responsible for altered thyroid hormone levels in hepatic cirrhosis. To examine this hypothesis, this study determined relationships between plasma glucose, glucagon, insulin, and insulin:glucagon ratio on one hand, and thyroid hormone concentrations on the other, in 51 subjects with hepatic cirrhosis. Significant negative correlations were noted between plasma glucagon and serum T3 (r = -0.418, p less than 0.001) as well as T3:T4 ratio (r = -0.627, p less than 0.0001), whereas significant positive correlations were observed between plasma glucagon and serum rT3 (r = 0.504, p less than 0.001) as well as rT3:T4 ratio (r = 0.644, p less than 0.0001). No such significant relationships were noted between either insulin, glucose and insulin:glucagon ratio on one hand and any of thyroid hormone indices on the other. Therefore, this study indicates that, in hepatic cirrhosis, circulating glucagon concentrations may play a major contributing role in induction of altered serum thyroid hormone concentration by influencing thyroid hormone metabolism.

Topics: Adult; Aged; Blood Glucose; Female; Glucagon; Humans; Insulin; Liver Cirrhosis; Male; Middle Aged; Thyroid Hormones; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Galactose; Humans; Liver Cirrhosis; Male; Middle Aged; Triiodothyronine, Reverse

The influence on the parameters of the thyroid gland BEI, T3-, T4- and TSH-serum level by the iodine-containing oral bile X-ray contrast remedy Falignost is demonstrated. Following a peripheral conversions inhibition from T4 to T3 by the contrast remedy the thyroid hormones in the serum are changed in different kind and duration. This influence is more expressed in patients with liver cirrhosis and continues. The risk of an iodine-induced hyperthyroidism is discussed. In the judgment of a possible disturbance of the function of the thyroid gland anamnestically is always to be asked the question about previous applications of iodine-containing drugs and it must be accordingly be taken into consideration.

Topics: Contrast Media; Dose-Response Relationship, Drug; Female; Humans; Iodobenzenes; Liver Cirrhosis; Male; Prospective Studies; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Aged; Child; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Middle Aged; Thyroid Diseases; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Basal thyroid hormone levels were measured in 68 women with liver cirrhosis (LC) of different etiology (alcoholic n = 34, posthepatitic B n = 9, PBC n = 5, cryptogenetic n = 18, M. Wilson n = 2). In addition the rise of TSH after 400 micrograms TRH was measured in 23 women with LC and compared with the data obtained from 17 women of a control group. There was no difference of the median T4-concentrations (LC 8.0 micrograms/dl versus 7.2 micrograms/dl) but a significant correlation of T4 to the grade of decompensation of LC. In contrast of T4 there was a marked decrease of T3 in LC-patients (109 ng/dl versus 143 ng/dl) and a rise of reverse T3 (0.21 ng/ml versus 0.13 ng/ml). The decrease of T3 and rise of reverse T3 equally correlated to the severeness of LC. TBG concentrations fell according to the grade of decompensation of LC and T4/TBG-quotient exhibited no difference to the control data (0.51 both). Though basal thyroid hormones and TSH show euthyroidism the significant augmented TSH release after TRH (delta-TSH 7.0 versus 3.2 microU/ml) indicate a status of latent hypothyroidism. In alcoholic cirrhosis the degree of TSH release was much higher than in non alcoholic cirrhosis. Estradiol and estrone levels correlated significantly negatively to T4, T3, estrone negatively to TBG and positively to reverse T3 but not to TSH and TSH release. Otherwise TSH release correlated positively to estradiol. The thyroid status in women with liver cirrhosis does not differ from the thyroid hormone profile found in men with cirrhosis.

Topics: Female; Hepatolenticular Degeneration; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Biliary; Middle Aged; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The prognostic value of thyroid function parameters (T3, T4, rT3 and the rT3:T3 ratio) and common liver tests (serum bilirubin, albumin and prothrombin activity) was investigated on hospital admission in 100 consecutive patients with predominantly non-alcoholic liver cirrhosis. Twenty-nine out of 100 patients had a well compensated cirrhosis and their mean values of thyroid tests were similar to those of 40 healthy controls. A low T3 syndrome was found in the remaining 71 decompensated patients. In these thyroid function parameters were correlated with serum bilirubin and prothrombin activity. Moreover mean values of all thyroid and liver tests, except serum albumin, were significantly different between survivors and nonsurvivors at 3 months. To evaluate the best cut-off value which allowed to predict the outcome of patients, the Receiver Operating Characteristics (ROC) curves were generated for each test by plotting the values obtained in survivors at 3 months (true positives) vs nonsurvivors (false positives). By holding the false positive errors within 10%, the highest percentage of true positive results (i.e. patients dead at 3 months) was observed for the rT3:T3 ratio, rT3 and serum bilirubin at a cut-off point of 0.841, 55 ng/dl and 3.5 mg/dl, respectively. According to the above cut-offs the rT3:T3 ratio had the best positive predictive value (74%; 95% confidence limits 60-90%) in comparison to rT3 and bilirubin.

Topics: Adult; Aged; Female; Humans; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Prognosis; Prospective Studies; Radioimmunoassay; Thyroid Function Tests; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The authors studied total and free circulating thyroid hormones, rT3, TBG and TSH behaviour on chronic liver disease in 11 subjects with cirrhosis of the liver with ascites(C.E.) and in 6 subjects with chronic active hepatitis (E.C.A.) in comparison with 15 healthy and euthyroid controls. Serum T3,FT3,T4 and FT4 levels were decreased significantly and serum rT3 values increased significantly both in the subjects with C.E. and in patients with E.C.A. Moreover no significantly changes of TSH and TBG levels has been found in 3 groups studied. These data suggest that the alteration of circulating thyroid hormones in chronic liver disease, may represent a compensatory way of reducing the patient's metabolic requirements.

Topics: Adult; Aged; Hepatitis, Chronic; Humans; Liver Cirrhosis; Middle Aged; Thyroglobulin; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Liver is one of the major sites of T4 metabolism. Several studies have reported low serum T3 concentrations and elevated reverse T3 (rT3) levels in hepatic cirrhosis. This study examined the influence of degree of the hepatocellular damage and the effect of improvement in clinical state on thyroid hormone concentrations in 44 cirrhotic patients. Low serum T4 and T3 as well as raised rT3 were observed in cirrhotic patients with advanced liver dysfunction alone. T3 resin uptake was increased in some of these patients suggesting decrease in serum thyroid-binding globulin concentration. In patients with histological changes but with normal liver function tests, serum T4, T3, and rT3 were not altered. Serum T3 and rT3 correlated significantly with liver function tests. T4, T3, and rT3 normalized on improvement in clinical status and liver function tests. Lowest levels of T4 and T3 with extremely high rT3 were seen in patients with extremely advanced liver dysfunction. In these patients, the mortality was high. Therefore, in hepatic cirrhosis, 1) T4 metabolism is altered with lowering of T4 and T3 and a rise in rT3. 2) These changes may be dependent on the degree of hepatocellular damage and reverse on improvement in liver function. 3) T4, T3, and rT3 levels are useful prognostic indices.

Topics: Adult; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Prognosis; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The relationship between chronic hepatosplenic schistosomiaisis (CHES) and circulating thyroid hormones as well as the TSH response to TRH were investigated in 41 hospitalized CHES patients and compared to those in 11 patients with non-CHES cirrhosis with severe hepatic failure. CHES patients were subdivided into 3 groups depending on the severity of parenchymal dysfunction, based upon a composite clinical and laboratory index. Angiographic and hemodynamic studies of CHES patients revealed altered hepatic arteriograms, suggesting a decreased arterial blood flow associated with an increased venous blood flow from the portal system. A significantly reduced serum concentration of total T4 (but not free T4) was only found in the cirrhotic patients. Compared to CHES groups I and II, CHES group III patients and the non-CHES cirrhotics had significantly lower mean serum T3 levels of 80 +/- 12 and 52 +/- 8 ng/dl, respectively. The serum rT3 concentration was elevated (69 +/- 6.2 ng/dl) only in the cirrhotic patients. Both basal and peak TSH levels after TRH were within the normal range for all 4 groups of patients. The basal (40.7 +/- 8.3 ng/ml) and peak (85.5 +/- 13.7 ng/ml) serum PRL levels T4-binding globulin after TRH administration were only elevated in the cirrhotic group. Although the mean T4-binding globulin values were lower in CHES group III (17.5 +/- 3.2 micrograms/ml) and in the non-CHES cirrhotic group (18.3 +/- 2.1 micrograms/ml) compared to those in groups I (21.8 +/- 2.2 micrograms/ml) and II (20.4 +/- 2.3 micrograms/ml), the differences between groups were not statistically significant. It was concluded that hemodynamic changes without parenchymal failure have little, if any, effect on the hepatic T4 5'-monodeiodination to T3, and that the low T3 and high rT3 state does not modify the pituitary secretion of TSH, presumably by a local (at the thyrotroph level) normal conversion of T4 to T3, even at very low peripheral T3 concentrations.

Topics: Chronic Disease; Female; Humans; Liver Circulation; Liver Cirrhosis; Liver Diseases, Parasitic; Male; Schistosomiasis; Splenic Diseases; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Concentrations of thyroid hormones and thyrotropin (TSH) were measured in sera of clinically euthyroid patients with various liver diseases and compared with normal controls. The mean serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) was significantly increased in patients with decompensated liver cirrhosis (p less than 0.01). This increase seemed to be dependent upon the hepatic damage, although it was not significant in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis. The mean serum concentration of 3,3',5-triiodothyronine (T3) was significantly decreased in patients with decompensated liver cirrhosis (p less than 0.05). However, in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis, the mean concentration of T3 was above the normal. The mean value of rT3/T3 ratios in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis were similar to that of normal controls, but in patients with decompensated liver cirrhosis, the mean value of rT3/T3 ratios was markedly higher than that of normal controls. The rT3/T3 ratios have little or no correlation with some standard liver function tests. These results suggest that marked alterations of peripheral conversion of thyroxine (T4) to rT3 or T3 may be found only in a state of decompensated liver cirrhosis among the various liver diseases.

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Hepatitis; Humans; Liver Cirrhosis; Liver Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adolescent; Adult; Humans; Infant, Newborn; Iodine; Kidney; Liver; Liver Cirrhosis; Nutrition Disorders; Thyroid Diseases; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

As first described in serious systemic illnesses isolated decreased T3 plasma concentration was related to impaired peripheral conversion of T4, to T3 with preferential production of reverse T3 (rT3). A "low T3 syndrome" was seen in 47 out of 109 patients with extra-thyroidal diseases. Metabolic state, TSH and TSH responses to TRH were normal despite of low T3 concentration. Euthyroidism seems mainly due to T4 itself in these patients.

Topics: Aged; Anorexia Nervosa; Diet, Reducing; Humans; Hypothyroidism; Kidney Diseases; Liver Cirrhosis; Neoplasms; Obesity; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diiodothyronines; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Liver Cirrhosis; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Chronic Disease; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Diiodothyronines; Female; Humans; Kinetics; Liver Cirrhosis; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse