Immunological and clinical characterization of patients with untreated euthyroid and hypothyroid autoimmune thyroiditis. Antibody spectrum, response to TRH and clinical study.

In a region of endemic goitres, 200 untreated patients in whom thyroid microsomal (MCHA) and/or thyroglobulin (TGHA) antibodies have been detected were analyzed and other organ specific autoantibodies were tested. Thyroid function was assessed by a TRH test in all of them. Patients with previous thyroid disease and patients with clinical or biochemical signs of thyrotoxicosis were excluded. In 58 (29%) of the patients diseases coexisted in which a high incidence of autoimmune reactions has been recognized. In the absence of the corresponding clinical disease, 13.7% of the patients had antibodies to parietal cells of the stomach, 3.1% had antibodies to adrenal cortex, 1% to steroid producing gonadal cells, 1% to pancreatic islet cells, and 0.5% of the patients had antibodies to striated muscle fibrils. The incidence of associated organ-specific autoantibodies was no higher in patients with hypothyroidism (34.6%) compared with patients who had a normal thyroid function (27.9%). The determination of a 'significant' thyroid antibody titre is discussed. In 24.5% of the 200 patients a form of hypothyroidism was recognized. Fifty of the patients with TGHA titres greater than or equal to 6400, and 56.2% of those with MCHA greater than or equal to 102 400 were hypothyroid. Patients with such titres of thyroid antibodies should be examined and followed up. Patients with associated islet cell or adrenal antibodies should be reinvestigated and followed up observing their glucose tolerance and adrenocortical function, respectively.

Micromethod of human thyrocyte cultures for detection of thyroid-stimulating antibodies and thyrotrophin.

The activation of adenylate cyclase of human thyrocytes in primary cell cultures and the release of cAMP into the medium are used to detect thyrotropin (TSH) and thyroid-stimulating antibodies (TSAb) in sera of patients with Graves' disease. Tissue digestion and cell dispersion are performed using a neutral protease of Bacillus polymyxa (Dipase II), which harvests more vital thyrocytes than does trypsin. The cells show an enhanced response to stimulation. The efficiency of the cell preparation and cultivation is increased by using microtest plates instead of culture flasks. By this minimization only 0.6-1.8 X 10(6) cells are needed to evaluate a single sample. Cyclic AMP concentrations are measured directly in the supernatant culture medium by a competitive protein binding assay with charcoal separation. The minimal detectable dose of bTSH is about 10 microU/ml. With increasing doses of bTSH cAMP concentrations rise to a peak at about 50 to 100 mU/ml, beyond which there is a gradual decrease of cAMP indicating negative cooperativity in the activating mechanisms. The 'long-acting thyroid stimulator' effect of TSAb is reflected by a protracted increase of cAMP to its maximal value. All 41 sera of hyperthyroid patients with Graves' disease were TSAb-positive, whereas sera of patients with toxic nodular goitre and euthyroid controls were TSAb-negative.

Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver.

[1,2-14C] Vinyl chloride and [1,2-14C] trichloroethylene were incubated with rat liver microsomes, NADPH and RNA (from yeast). Whereas trichloroethylene metabolites were irreversibly bound to proteins in microsomal incubations to a higher extent than vinyl chloride metabolites, irreversible binding to RNA was lower for trichloroethylene metabolites. Hydrolysis of the RNA which was reisolated from microsomal incubations with 14C-vinyl chloride or 14C-trichloroethylene and separation of the nucleosides showed different alkylation products arising from vinyl chloride and from trichloroethylene, characteristic for vinyl chloride being formation of 1,N6-ethenoadenosine and 3,N4-enthenocytidine. The different reactivities of metabolites of vinyl chloride and of trichloroethylene prompted a comparison of the oncogenic effects of both compounds against the rat liver cell. Newborn rats were exposed for 10 weeks to 2000 ppm vinyl chloride or trichloroethylene (8 h/day; 5 days/week). After this period livers of the animals were stained for nucleoside-5-triphosphatase. Whereas the vinyl chloride exposed rats showed focal hepatocellular deficiencies in this enzyme, which are supposed to represent an early sign of malignancy, no such changes were induced by trichloroethylene exposure. The data therefore suggest differences between the hepatocarcinogenic activity of vinyl chloride and possible effects of trichloroethylene on the liver.