Serum levels of TSH, thyroxine-binding globulin (TBG), T4, T3 and reverse T3 (rT3) were measured in 36 patients with fatty liver disease, 11 patients wih chronic persistent hepatitis, 17 patients with chronic active hepatitis, and 29 patients with liver cirrhosis. TBG was significantly above normal levels in both groups of chronic hepatitis, the slight concomitant T4 and T3 increase was significant only for T4 in chronic persistent hepatitis. A significant decrease in T4 and T3 concentration was found in fatty liver disease and in hepatic cirrhosis. A shift in T4 conversion to rT3 could exclusively be demonstrated for the group of hepatic cirrhosis, reflected by a significant increase in rT3. As our findings indicate normal TSH levels and a lack of clinical signs of hypothyroidism in chronic liver disease, the possibility of diverse regulating changes must be considered.

Alpha-Globulins↗

PubMedDate not supplied

Solubilized TSH-receptor: its usefulness for the radioligand receptor assay for TSH and TSH-displacing antibody.

The usefulness of solubilized TSH-receptor for measuring TSH and TSH-displacing antibodies (TDA) in a radioligand receptor assay (RRA) was investigated. Crude thyroid membranes were solubilized with Triton X-100. A soluble protein fraction was isolated by DEAE-Sephadex A-50 ion-exchange chromatography. The binding of 125I-TSH to the solubilized fraction was studied. It was maximal after 45 min at 37 C, whereas at 4 C a similar binding was observed after at least 17 h. The binding was inhibited by Ca2+ and Mg2+ with concentrations higher than 1 mM and by NaCl in the concentration range 17-150 mM. No inhibition of binding was found with normal serum up to 100 microliter. In contrast, 1.5 microliter of a Graves' disease serum showed significant inhibition. Using the system to measure TSH in serum, as low as 10 microunits TSH could be estimated. Compared to an RRA using thyroid membrane fractions, the sensitivity for TSH in serum as well as for TDA is increased at least tenfold in our system.

Calcium↗

PubMedDate not supplied

Binding of solubilized human TSH-receptor protein by peripheral blood lymphocytes of patients with Graves' disease.

Peripheral blood lymphocytes (PBL) from patients with hyperthyroidism due to Graves' disease (GD) were investigated for the ability to bind radioiodinated TSH receptor protein as hypothetical autoantigen (ABL). Thyrotropin-displacing antibody (TDA)-positive patients, who relapsed and were investigated shortly after starting antithyroid drug therapy, as well as TDA-positive patients with a first diagnosis of GD, who were investigated before starting therapy, showed significantly increased numbers of ABLs (0.2 +/- 0.17%, p less than 0.01 and 0.15 +/- 0.08%, p less than 0.001, respectively) when compared to controls (0.018 +/- 0.016%). In contrast, TDA - negative patients had no significant increase of ABLs (0.08 +/- 0.09%). Preincubation of PBLs with excess unlabelled antigen and nylon wool filtration of PBLs, reduced the number of ABLs markedly. Blocking of the binding sites on the lymphocytes with anti-Ig serum and blocking of the antigen itself by TSH depleted PBLs almost totally from ABLs. The present data indicate that: i) there are lymphocytes of B-cell characteristics capable of binding TSH-receptor; ii) there is a correlation between appearance of ABLs in hyperthyroid GD patients and the detection of TDA in patients' sera; iii) in Hashimoto, toxic nodular goiter and in some normals, a small amount of TSH receptor binding ABLs are detectable.

Graves Disease↗

PubMedDate not supplied

Isolation and characterization of mononuclear cells from various thyroid tissue specimens.

Extensive studies of humoral and cell mediated autoimmune responses to thyroid antigens have been performed in order to understand the underlying mechanisms of autoimmune thyroid disorders. Very little is known, however, about the nature of the lymphocyte subpopulations in the thyroid gland and their possible involvement in the pathogenesis of thyroid diseases. We have developed a Percoll gradient technique to separate mononuclear cells from thyroid cells of resected thyroid glands. Thyroid tissue was minced, incubated with Dispase and passed through a tissue sieve. The filtrate was layered onto a four step discontinuous Percoll gradient (densities 1.140, 1.077, 1.061, 1.030 g/ml). Thyroid cells appeared in band II and mononuclear cells in band III. Mononuclear cells were characterized using the monoclonal antibodies OKT-3, OKT-8, OKI-a and OKM-1, and the levels of these populations in peripheral blood and thyroid tissue compared. Patients have been classified by conventional clinical, immunological and histological criteria. The studies involved thyroid tissues from 8 patients with euthyroid nodular goitre, 7 patients with Graves' disease and 1 with Hashimoto's thyroiditis. In the thyroid tissue of non-autoimmune thyroid diseases we find significantly less OKT-3+ cells compared to peripheral blood. In thyroid tissue of autoimmune thyroid diseases there are significantly less OKT-8+ cells compared to peripheral blood. These preliminary results might be linked to the hypothesis of decreased suppressor T-cell activity in autoimmune thyroid disease.

Cell Separation↗

PubMedDate not supplied

Natural cytotoxicity of peripheral blood leukocytes from normal subjects and patients with Hashimoto's thyroiditis against human adult and fetal thyroid cells.

Natural cytotoxicity of human peripheral blood leukocytes against fetal and adult human thyroid cells was investigated in vitro. Natural killer (NK) cell activity was determined at various effector: target cell ratios in a standard 51Cr release assay with human thyroid cells as targets. The effector cells were unfractionated peripheral blood mononuclear cells obtained by Hypaque-Ficoll gradient centrifugation. We have demonstrated that peripheral blood leukocytes from normal subjects and patients with Hashimoto's thyroiditis exhibit natural cytotoxicity against both human fetal and adult thyroid cells. This was effector: target cell ratio and incubation time dependent. Although there was a tendency for increased killing of fetal thyroid cells by peripheral blood leukocytes from patients with Hashimoto's thyroiditis compared to age/sex matched normal subjects this was not significant and there were no significant differences between the two groups for killing of adult thyroid cells. A possible role for natural cytotoxicity in progressive thyroid tissue destruction in Hashimoto's thyroiditis is discussed.

Adolescent↗