Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a recent hypothesis that thyroxine (T4), secreted by the thyroid gland under physiological conditions, is mono-deiodinated in extrathyroidal sites to form the more active 3, 3', 5-tri-iodothyronine (T3) before exerting biological activity at target tissue level. Futhermore, circumstantial evidence suggests that the liver is an important site for the extra-thyroidal conversion of T4 to T3. Thyoid hormone pathophysiology in liver disease is therefore of interest. Patients with hepatic cirrhosis have normal or raised plasma T4 concentration and markedly reduced plasma T3 concentration. Free hormone measurement reflect this pattern and three is kinetic and other evidence to support the concept that extra-thyroidal conversion of T4 to T3 is reduced in patients with liver dysfunction. Comparable finding have however been reported in patients with other non-hepatic chronic systemic diseases but, unlike in hepatic cirrhosis, serum thyrotropin (TSH) is not increased. Increased serum TSH is found in hepatic cirrhois and is often accompanied by an abnormal TSH response to thyrotropin-releasing hormone (TRH) suggesting, in addition, disordered hypothalamic-pituitary control of thyroid function in these patients. Thyroid physiology is clearly markedly disturbed in hepatic cirrhosis but no single hypothesis adequately accounts for all the observed abnormalities. The recent finding of increased plasma 3, 3', 5-tri-iodothyronine (reverse t3; rT3) concentration in hepatic cirrhosis may ulimately clarify our understanding.
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PMID:Thyroid function in chronic liver disease. 11 92

The plasma growth hormone (hGH) responses to an intravenous challenge of 400 micrograms of thyrotropin-releasing hormone (TRH) were evaluated in 14 normal controls and in 29 chronic alcoholic men. The normal controls had either a minimal or no hGH response to TRH, having basal hGH levels of 0.9 +/- 0.2 ng per ml and peak hGH levels of 2.0 +/- 0.5 ng per ml. In contrast, the chronic alcoholic men had a basal hGH level of 2.8 +/- 0.4 ng per ml, 3 times the basal level of the normal controls (P less than 0.01). The peak hGH response of the alcoholic men was 7.4 +/- 1.5 ng per ml (P less than 0.01). The 29 alcoholic men could be divided into two groups based upon the presence or absence of cirrhosis as determined by liver biopsy. The 16 alcoholic men with cirrhosis had greater basal hGH levels (3.5 +/- 0.6 ng per ml) and peak hGH levels (9.5 +/- 2.3 ng per ml) than did the 13 alcoholic men without cirrhosis (basal hGH 2.1 +/- 0.6 ng per ml, peak hGH 4.9 +/- 1.5 ng/ml). Plasma estradiol levels were similar in the normal controls and in the alcoholic men. In contrast, plasma estrone was greater in the alcoholic men (32.2 +/- 3.5 pg per ml) than in the normal controls (18.9 +/- 1.8 pg per ml) (P less than 0.05). However, when the plasma estrone levels of alcoholic men with cirrhosis were compared to those of the alcoholic men without cirrhosis no difference existed. Thus it is difficult to ascribe the increased hGH responses of the cirrhotic alcoholic men when compared to those of the noncirrhotic alcoholic men as being a result of increased basal estrogen levels.
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PMID:Thyrotropin-releasing hormone (TRH)-induced growth hormone (hGH) responses in cirrhotic men. 12 3

A significant increase of basal plasma prolactin levels (radioimmunoassayed) in 75 patients with liver cirrhosis was found in comparison to 50 male controls (8.5+/-4.5 (SD) vs. 5.5+/-1.7 ng/ml p less than 0.001). The extent and incidence of hyperprolactinaemia in 48 patients with alcoholic cirrhosis was more pronounced than in 27 cases of cirrhosis of non-alcoholic aetiologies (mean 9.7+/-4.8 vs. 5.7+/-2.1 ng/ml). No relation to ascites formation as well as to the development of gynaecomastia was apparent. Prolactin release following thyrotropin-releasing hormone was markedly enhanced in alcoholic as compared to non-alcoholic cirrhosis. Possibly hyperprolactinaemia and increased pituitary hormone reserve reflects hyperoestrogenism but changes of the hypothalamic regulation cannot be excluded as yet.
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PMID:Plasma prolactin and prolactin release in liver cirrhosis. 40 18

To evaluate abnormal secretion of growth hormone (GH) in cases of liver diseases, the authors performed a loading test of growth hormone-releasing factor (GRF) and approximately one week later, a loading test of thyrotropin-releasing hormone (TRH), and measured serum GH in 15 cases of liver cirrhosis (LC), 5 with chronic active hepatitis (CAH), and 5 controls. In the TRH test, 8 of 15 LC patients showed a peak GH value of 6 ng/ml or more and were classified as the TRH-responder group (LC-R). Seven other LC patients showing a peak GH value of less than 6 ng/ml were classified as the TRH-non-responder group (LC-NR). None of the CAH cases or controls showed a peak GH value of 6 ng/ml or more. In GRF test, the response of GH was poor in all 8 in the LC-R group. The responses in the LC-NR group were significantly greater than those in the LC-R group from 15 to 90 minutes after the GRF loading. In the LC-R group, greater impairment of liver function was indicated by total bilirubin, serum protein and cholinesterase values compared to the LC-NR group. Fischer's ratio was significantly lower in the LC-R group. In cases of liver diseases, Fischer's ratios negatively correlated with the peak GH values in the TRH test (r = -0.679, P less than 0.01). These results suggest that in LC cases showing a paradoxical GH response to TRH, the GH response to GRF which is a GH stimulatory hormone, is decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal GH secretion in liver cirrhosis: evaluation of using GRF test and TRH test. 162 79

In order to improve understanding of factors that may contribute to reduced serum T4 in non-thyroidal illnesses, we have studied baseline thyroid function, serum TSH response to thyrotropin-releasing hormone (TRH), and/or increase in thyroidal radioiodine uptake and serum T4 after parenteral administration of TSH in 12 patients with decompensated liver cirrhosis. Ten age and sex matched normal volunteer subjects served as controls. Compared to control subjects, patients with hepatic cirrhosis had significantly lower mean serum total T3 (ng/dl, mean +/- SD, 56 +/- 31 vs. 147 +/- 25, P less than 0.001), total T4 (microgram/dl, 4.3 +/- 1.5 vs. 8.8 +/- 0.74, P less than 0.001), and higher TSH (microU/ml, 3.0 +/- 1.2 vs. 1.6 +/- 0.73, P less than 0.05). Serum TSH response to TRH (400 micrograms I.V.) was abnormal in seven of 12 patients so studied. The peak TSH post-TRH was subnormal in one patient and normal but delayed in six patients. The mean baseline 24 h thyroid 131I uptake was not significantly different between the two groups under study (17 +/- 12% in cirrhosis patients vs. 25 +/- 10% in normal subjects). However, six patients with hepatic cirrhosis had clearly subnormal (less than 15%) 24 h thyroid radioiodine uptake (normal range 15-47%). The mean increase in 24 h thyroid radioiodine uptake and serum T4 at about 40 h after exogenous TSH (0.1 U/kg body weight i.m.) was lower in liver cirrhosis patients than that in normal subjects, but the difference was not significant statistically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A study of thyroidal response to thyrotropin (TSH) in decompensated liver cirrhosis. 248 74

Patients with chronic liver diseases were evaluated for: 1) the ability of somatostatin to affect the thyrotropin-releasing hormone (TRH) induced growth hormone (GH) rise; 2) the competence of luteinizing-hormone releasing hormone (LH-RH) to release GH; 3) the non-specific releasing effect of TRH and LH-RH on other anterior pituitary (AP) hormones. In 6 patients, infusion of somatostatin (100 micrograms iv bolus + 375 micrograms i.v. infusion) completely abolished the TRH (400 micrograms i.v.)-induced GH rise; in none of 12 patients, of whom 7 were GH-responders to TRH, did LH-RH (100 micrograms i.v.) cause release of GH; 4) finally, LH-RH (12 patients) did not increase plasma prolactin (PRL) and TRH (7 patients) did not evoke a non-specific release of gonadotropins. It is concluded that: 1) abnormal GH-responsiveness to TRH is the unique alteration in AP responsiveness to hypothalamic hormones present in liver cirrhosis; 2) the mechanism(s) subserving the altered GH response to TRH is different from that underlying the TRH-induced GH rise present in another pathologic state i.e. acromegaly, a condition in which the effect of TRH escapes somatostatin suppression and LH-RH evokes GH and PRL release.
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PMID:Growth hormone response to thyrotropin-releasing hormone in liver cirrhosis: unique alteration in anterior pituitary responsiveness to hypothalamic hormones. 612 95

This study included 35 patients with liver cirrhosis, 23 patients with hyperthyroidism, 12 with hypothyroidism, and 2 with other endocrine disorders. In the various endocrine disorders an appreciable amount of triiodothyronine (T3) was excreted into the urine but the daily excretion was fairly constant in each patient. Urinary excretion of T3 was negligible or depressed in hypothyroidism, but increased with a rise in the serum level of T3. Serum and urinary T3 decreased in liver cirrhosis, but the serum thyroxine (T4) level was within the normal range. When the cirrhosis patients were divided into 3 groups according to the urinary excretion of T3, a decrease of urinary T3 was associated with a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of lh a decrease in the serum levels of T3 and free T3. An increase of serum thyroid-stimulating hormone (TSH) either before or after injection of thyrotropin-releasing hormone (TRH) was inversely correlated with a decrease of serum and urinary T3. The decrease of serum and urinary T3 was correlated with the magnitude of liver damage as judged by indocyanine green retention and a decreased urinary excretion of cyclic adenosine 3',5'-monophosphate. In vitro experiments indicated that rat liver, as compared to the kidney, heart and skeletal muscle, strongly converts T4 to T3, but this activity is greatly reduced by liver damage induced by ligation of the bile duct. It is suggested that patients with liver cirrhosis are, to some extent, in a state resembling subclinical hypothyroidism because of inability of the liver to metabolize a sufficient amount of T3 from T4.
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PMID:Thyroid hormone metabolism in patients with liver cirrhosis, as judged by urinary excretion of triiodothyronine. 625 45

Prolactin is known to have renal sodium retention properties in animals. In man, only two studies have suggested a similar effect in healthy volunteers or in patients with microprolactinoma. Since hyperprolactinemia is frequently observed in liver disease, this prospective study of 19 patients evaluated the influence of prolactin on urinary electrolytes excretion in cirrhosis. Basal hyperprolactinemia was found in 14 out of 19 cases. The effect of serum prolactin elevation on renal sodium and potassium excretion was studied in all patients after thyrotropin-releasing hormone stimulation (200 micrograms), with seven consecutive hourly urinary samples. Patients were separated into two groups according to amount of prolactin discharge after thyrotropin-releasing hormone injection. Group I included patients with "low prolactin release", defined as the difference between basal and peak prolactin values (delta prolactin) < 1000 mu u/ml (n = 8), and no change in natriuresis could be observed. In contrast, in group II with a "high PRL release" (delta prolactin > 1000 mu u/ml, n = 11), significant reductions in urinary sodium (p < 0.01) and potassium (p < 0.02) excretion were observed, which lasted until the third hour after thyrotropin-releasing hormone injection. A significant correlation was found between peak prolactin values and the decrements of natriuresis (r = 0.70, p < 0.02). The pattern of urinary electrolyte changes and the stability of the ratio UK/UK+Na suggest a possible sodium-retaining effect of prolactin localized proximally to the distal tubule.
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PMID:Indirect evidence to suggest that prolactin induces salt retention in cirrhosis. 783 3

We have developed a convenient method combining fast protein liquid chromatography (FPLC) with sensitive radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) to separate and identify TRH and its metabolite histidyl-proline diketopiperazine (CHP) and applied this to study inactivation of TRH by blood extracts from patients with liver cirrhosis (LC) and acute edematous pancreatitis (AP). Blood samples spiked with TRH and CHP were extracted by cold methanol and injected on a reverse-phase FPLC column. A linear gradient was applied for separation. Subsequent analyses of fractions by RIA for TRH revealed that only fractions 9-10 contained TRH. Separation by retention time (9.9 +/- 0.8 min for TRH, 10.5 +/- 0.6 min for CHP, mean +/- SEM) was highly reproducible. For degradation studies, pooled sera from patients with LC and AP were incubated with TRH and CHP for 60 min. Inactivation of TRH was less rapid in the presence of blood extract from LC patients than that from normal subjects or AP patients. CHP was more stable than TRH. These data suggest that activity of TRH-degrading enzymes is reduced in liver disease, whereas it does not appear to be altered in AP. Degradation of CHP does not closely reflect metabolic processing of its major precursor. This rapid and sensitive method may be applicable for further investigations on the metabolism of TRH in organic fluids.
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PMID:A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases. 812 15

Previous in vitro studies have demonstrated zinc (Zn++) inhibition of basal and of potassium (K+) or thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH-stimulated PRL in healthy men. We found that Zn++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn++ levels.
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PMID:Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men. 1081 35


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