DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

Abstract

A new bioassay is described for detecting the growth stimulating immunoglobulins (TGI) that contribute to goitre formation in human thyroid autoimmune diseases. It measures the incorporation of tritiated thymidine into intact rat thyroid follicles grown in tissue culture. This radiometric assay demands much less technical skill than the cytochemical bioassays (CBA) previously employed. It has good reproducibility and the techniques and apparatus are available in many clinical laboratories. Immunoglobulins (Igs) from 68% of patients with goitrous Graves' disease were positive, in proportion with goitre size, and this showed no correlation with T3 levels, or three accepted methods for conventional thyroid stimulating antibodies. Non-toxic nodular goitre cases gave positive results in 3/9 who had recurrences after one or more thyroidectomies and in 1/10 cases of familial simple goitre. All normal subjects and all endemic goitre cases were negative as well as 21 cases of sporadic non-toxic nodular goitre. Although it is less sensitive than the 'growth CBA' it clearly emphasizes the essential difference between the intensity of growth stimulus which leads to the regular hyperplasia of thyroid epithelium seen in Graves' thyrotoxicosis and the disorganized and metabolically uncoordinated hyperplasia typical of non-toxic nodular goitre.

Thyroid growth-stimulating immunoglobulins in goitrous disease: relationship to thyroid-stimulating immunoglobulins

“…This is in contrast to the findings reported using [3H]thymidine incorpora¬ tion assays, although they could detect TGI in a majority of patients who had goitrous Graves' disease, found TGI in only 4:40 (10%) (Chiovato et al 1983) 2:17 (12%) (Valente et al 1983a) and 3:15 (20%) (Schatz et al 1983) of non-toxic goitre. An exception was the report of Rotella et al (1984) who found TGI in 16/30 (53%) with nontoxic simple goitre.…”

“…Although the cyto¬ chemical assay system does not have the facility to be applied to the simultaneous measurement of TGI in large numbers of samples as is the case of [3H]thymidine incorporation assays (Chiovato et al 1983;Valente et al 1983a;Schatz et al 1983Schatz et al , 1984 it is considerably more sensitive than these assays. Thus, TGI measured by CBA in the pres¬ ent study was detectable not only in 100% of patients tested who had goitrous Graves' disease or toxic multinodular goitre but in 50% who had hyperthyroidism with autonomously functioning thyroid nodules.…”

“…Since this first report, thyroid growth stimulating immunoglobulins (TGI) have also been detected in IgG concentrates prepared from human plasma using [3H]thvmidine uptake in cultured rat thyroid cells (Chiovato et al 1983;Valente et al 1983 a;Rotella et al 1984) or por¬ cine thyroid follicles (Schatz et al 1983). Although stimulators of thvroid function and growth ap¬ pear to act through different pathways (Drexhage et al 1982;Valente et al 1983b) they have been shown to be simultaneously present in varying proportions in thyroid disease (Valente et al 1983a).…”

Bovine thyrotropin inhibits DNA synthesis inversely with stimulation of cyclic AMP production in cultured porcine thyroid follicles.

“…The inhibition by TSH was observed in human thyroid cells (Westermark et al, 1979). The stimulation was observed in rat, guinea pig and dog thyroid cells (Speight et al, 1968;Nitsch and Wollman, 1980b;Drexhage et al, 1980;Drexhage et al, 1981;Chiovato et al, 1983;Roger et al, 1983). In porcine, rabbit and sheep thyroid cells, bovine TSH does not stimulate (Fayet and Hovsepian, 1979;Nilson et al, 1980;Fayet and Hovsepian, 1980;O'Conner et al, 1980;Kaneko, 1981).…”

Thyroid growth modulating factors in the sera of patients with simple non-toxic goitre

“…Following the pioneering work of Doniach's group (Drexhage et al 1980) several laboratories have validated the hypothesis that goitrous en¬ largement in some thyroid disorders could be induced by autoantibodies mimicking TSH in its growth inducing effect (Chiovato et al 1983;Schatz et al 1983;Valente et al 1983). In these studies, the presence of thyroid growth immuno¬ globulin in the goitrous Graves' disease is parti¬ cularly well documented.…”