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)

While 3, 3', 5'-triiodothyronine (reverse T3, rT3) has been detected both in human serum and in thyroglobulin, no quantitative assessment of its metabolic clearance rate (MCR), production rate (PR), or secretion by the thyroid is yet available. This study examines this information in euthyroid subjects and evaluates it in light of similar information about two other iodothyronines in the thyroid: 3, 5, 3'-triiodothyronine (T3) and thyroxine (T4). Thus, it was noted that rT3 is cleared from human serum at a much faster rate than are T3 and T4; the mean (+/-SE) MCR of rT3 was 76.7+/-5.4 liters/day in 10 subjects, whereas MCR-T3 and MCR-T4 in 8 of them were 26.0+/-2.2 liters/day and 1.02+/-0.06 liters/day, respectively. Therefore, even though the mean serum concentration of rT3, 48+/-2.8 ng/100 ml, was much lower than that (128+/-6.7 ng/100 ml) of T3, the mean PR-rT3 (36.5+/-2.8 mug/day) and the mean PR-T3 (33.5+/-3.7 mug/day) were similar; in comparison, the mean serum concentration and PR of T4 were 8.6+/-0.5 mug/100 ml and 87.0+/-3.9 mug/day, respecitvely. These data and those on the relative proportion of rT3, T3, and T4 in 10 thyroid glands were used to assess the significance of the contribution of thyroidal secretion to PR-rT3 and PR-T3. It was estimated that whereas thyroidal secretion may account for about 23.8% of serum T3 (or PR-T3), it may account for only about 2.5% of serum rT3 (or PR-rT3). Since peripheral metabolism of T4 is the only known source of rT3 and T3 other than the thyroidal secretion, it could be calculated that as much as 73.0 mug or 84% of daily PR-T4 may normally be metabolized by monodeiodination either to T3 or to rT3. MCR and PR of various iodothyronines were also examined in five cases with hepatic cirrhosis, where, as documented previously, serum rT3 may be elevated while serum T3 is diminished. The mean MCR-rT3 in these cases (41.0 liters/day) was clearly (P is less than 0.005) less than that (76.7 liters/day) in normal subjects. This was the case at a time when the mean MCR-T3 (26.7 liters/day) and the mean MCR-T4 (1.19 liters/day) did not differ from those (vide supra) in normal subjects. Distinct from changes in MCRs, the mean PR-rT3 (33.0 mug/day) was similar to, and the mean PR-T3 (10.1 mug/day) and the mean PR-T4 (66.4 mug/day) were much less than, the corresponding value in normal subjects. Furthermore, while the ratio of PR-rT3 and PR-T4 (rT3/T4) in individual patients was either supranormal or normal, the ratio of PR-T3 and PR-T4 (T3/T4) was clearly subnormal. The various data suggest that: (a) just as in the case of T3, the thyroid gland is a relatively minor source of rT3; peripheral metabolism of T4 is apparently its major source; (b) the bulk of T4 metabolized daily is monodeiodinated to T3 or to rT3; (c) monodeiodination may be an obligatory step in metabolism of T4; (d) monodeiodination of T4 to rT3 is maintained normal or is increased in hepatic cirrhosis at a time when monodeiodination of T4 to T3 is decreased.
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PMID:An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man. 93 9

Using immobilized anti-C3 antibody and an enzyme immunoassay, sera from 26 patients (eight with systemic lupus erythematosus (SLE), four with Hashimoto's thyroiditis, eight haemophiliacs and six with post-hepatitis cirrhosis) containing high levels of circulating immune complexes (IC) were selected. The IC were precipitated with 2.5% polyethylene glycol, washed, treated with acid buffer, neutralized and tested using an enzyme immunoassay in parallel with the original sera for antibody activity against a panel of antigens: human myosin and thyroglobulin, mouse actin and tubulin, calf thymus DNA and trinitrophenyl coupled to bovine serum albumin (TNP/BSA). It was found that all the isolated IC may contain IgG, IgA and IgM antibodies reacting with actin tubulin and TNP/BSA and also, depending upon the disease, antibodies reacting with some of the other antigens of the panel. By comparison to the antibodies present in the original sera, higher titers of antibodies were found in the isolated IC while some antibody specificities not detected in a given serum were occasionally noted in the isolated IC. The antibodies present in the IC seem to possess characteristics similar to those of polyreactive human natural autoantibodies. It is concluded that natural autoantibodies participate actively in the formation of IC found in pathological sera.
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PMID:Enzyme immunoassay analysis of antibody specificities present in the circulating immune complexes of selected pathological sera. 305 7

To further evaluate thyroid function in patients with liver disease, we have measured total and free T3 and T4, thyroxine binding globulin, basal and thyrotropin releasing hormone-stimulated thyrotropin and thyroglobulin antibodies in 33 patients with liver cirrhosis, in 22 with chronic hepatitis and in 30 healthy controls. All the patients but one were clinically euthyroid. T3, FT3, T3/thyroxine binding globulin and T4/thyroxine binding globulin ratios and thyrotropin after thyrotropin releasing hormone were significantly reduced, while FT4, thyroxine binding globulin and thyrotropin were significantly increased in liver cirrhosis. In chronic hepatitis group, FT3 and T3/thyroxine binding globulin ratio were significantly lower and thyroxine binding globulin and FT4 were higher than in healthy controls. The between patients comparison revealed a significantly lower T3, FT3, T3/thyroxine binding globulin and T4/thyroxine binding globulin ratios and delta thyrotropin in cirrhotics. Thyroglobulin antibodies were present at high titre only in two patients one of whom having evidence of Hashimoto's thyroiditis with subclinical hypothyroidism. The correlation coefficient between T4/thyroxine binding globulin ratio and FT4 were lower in patients than in controls. Furthermore an abnormal thyrotropin response to thyrotropin releasing hormone was shown in 10 cirrhotics and in four patients with chronic hepatitis. Serum T3 significantly correlated with serum bilirubin, albumin, and prothrombin time in both groups of patients. The present data confirm the existence of several abnormalities of thyroid function tests in patients with chronic liver disease, although showing that euthyroidism is almost always maintained, probably as a result of low-normal FT3 and high-normal FT4. Furthermore, T3 serum levels appear to parallel the severity of liver dysfunction.
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PMID:Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. 640 5

A RIA for the antithyroid drug methimazole [1-methyl-2-mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH-MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.
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PMID:Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole. 654 90

In view of the widespread use of serum thyroglobulin determination in the follow-up of patients with differentiated thyroid carcinoma, the influence of acute and chronic liver disease on serum thyroglobulin concentration was investigated in thirty-seven consecutive patients with histologically proven alcoholic liver cirrhosis and twenty-three patients with acute non-alcoholic hepatitis. Seventy-four healthy volunteers served as controls. Serum thyroglobulin concentration was significantly elevated in cirrhosis: median 29.5 micrograms/l, (range 4.3-94.0 micrograms/l) compared to controls: median 16.0 micrograms/l, (range 4.8-89.6 micrograms/l), (P less than 0.001). Serum thyroglobulin concentration in patients with acute hepatitis: median 16.2 micrograms/l, (range 7.9-70.0 micrograms/l) was not significantly different from controls. The level of free-T3-index was significantly reduced and the level of free-T4-index was significantly elevated in both cirrhosis and hepatitis compared to controls. Serum TSH concentration was significantly elevated in cirrhosis compared to hepatitis and controls. Serum thyroglobulin levels were positively correlated to levels of free-T3-index (r = 0.35, P less than 0.05) and T3/T4-ratio (r = 0.40, P less than 0.05) but not to levels of serum TSH or free-T4-index or any of the liver function tests in any of the groups. In conclusion, our results do not clearly indicate whether the elevated serum thyroglobulin level in cirrhosis was caused by an impaired elimination and/or an increased secretion from the thyroid gland. The increase in serum thyroglobulin concentration in chronic alcoholic liver disease was not of a magnitude likely to cause misinterpretation of results obtained during the follow-up of patients with differentiated thyroid carcinoma.
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PMID:Serum thyroglobulin in acute and chronic liver disease. 688 38

Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy.
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PMID:Non-functioning parathyroid gland carcinoma: case report. 2226 88

We report the case of a 26-year-old woman with a 19 cm malignant hepatic neoplasm with morphological features that closely resembled a follicular thyroid carcinoma. Despite this, it was interpreted as a cholangiocarcinoma due to the absence of a primary thyroid tumor and the lack of thyroglobulin and TTF-1 immunoreactivity by the hepatic tumor. The left hepatic lobectomy specimen showed an encapsulated and multinodular gray-white mass with cystic and hemorrhagic areas. Microscopically, it displayed predominant macro and microfolicullar patterns with focal solid, trabecular and insular areas. The small and distended follicles contained a colloid-like secretion and were lined by low cuboidal cells with scant cytoplasm, round or oval hyperchromatic nuclei with fine chromatin. The solid areas, trabecular and insular structures were similar to those of follicular or papillary thyroid carcinomas. In addition, some of the neoplastic cells had clear nuclei with occasional grooves. The tumor was positive for cytokeratin (CK) 7, CK 19 and CD138, and negative for TTF-1, thyroglobulin, Hepar-1, Glypican-3, alpha-fetoprotein and neuroendocrine markers. A thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. Although, the residual hepatic parenchyma was initially not cirrhotic, the patient eventually developed cryptogenic cirrhosis. The patient received adjuvant chemotherapy and died of metastatic disease 18 months after surgery. The thyroid-like pattern broadens the morphologic spectrum of cholangiocarcinoma.
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PMID:Thyroid-like cholangiocarcinoma of the liver: an unusual morphologic variant with follicular, trabecular and insular patterns. 2310 64

Cardiovascular symptoms remain the most common presenting features and leading causes of death in hyperthyroidism. We report a young female with reported thyroid disease and medication noncompliance presenting with atrial fibrillation, severe atrioventricular regurgitation, severely dilated right heart with reduced function, and moderate pulmonary hypertension (PH), which was further complicated by congestive liver injury with ascites and pancytopenia. Thyroid work-up revealed suppressed TSH, elevated free T4 and T3 along with elevated anti-thyroglobulin antibodies, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin, suggesting Graves' thyrotoxicosis. Ultrasound of the abdomen was suggestive of liver cirrhosis and ascites, which was thought to be cardiac cirrhosis, after multiple negative work-ups for alternate causes of cirrhosis. Ascitic fluid analysis revealed portal hypertension as the cause. The patient was restarted on antithyroid medication with gradual improvement of thyroid function and in clinical and echocardiogram findings. In contrast to primary PH that carries a poor prognosis and has limited treatment options, PH due to Graves' disease carries a good prognosis with prior reports of resolution after appropriate treatment, emphasizing the importance of early recognition. Also, unlike cirrhosis caused by alcohol or viral hepatitis, the effect of cardiac cirrhosis on overall prognosis has not been clearly established.
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PMID:Hyperthyroidism with Biventricular Heart Failure and Cirrhotic Transformation of the Liver. 3062 46