The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimoto's thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti-thyroglobulin (TgAb), second colloid antigen antibodies (CA2-Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth-stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea-pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL-5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2-Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth-stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P less than 0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose-response CBA showed a good relation with clinical goitre size (r = 0.63; P less than 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimoto's lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition.

The last 2 decades it has become clear that iodine deficiency has a modulating effect on the thyroid autoimmune response in humans. Also, in animals that spontaneously develop autoimmune thyroid disease, evidence is accumulating that a low iodine intake can modulate thyroid autoimmune reactivity. However, it is still not clear what the effect of a low iodine intake on thyroid autoimmune reactivity is in normal nonautoimmune animals. To study the relationship of a dietary low iodine intake on the thyroid autoimmune reactivity in nonautoimmune animals, normal Wistar rats (female) were kept on an enriched iodine diet (daily iodine intake of 100 micrograms iodine), a "for our area normal" (conventional) diet (COD; daily iodine intake of 7 micrograms iodine), a low iodine diet (LID; 2 days of 1% KCLO4, followed by iodine-deficient drinking water/pellets), or an extremely low iodine diet (LID+; 1% KCLO4 continuously in the drinking water and iodine-deficient pellets). The enriched iodine diet rats were euthyroid (T3, approximately 8 nM/liter: T4, approximately 50 nM/liter; TSH, approximately 2 ng/ml), had a normal thyroid weight (approximately 12.5 mg), and showed only minimal signs of local thyroid immune reactivity; low numbers of intrathyroidal dendritic cells (DC; approximately 35 DC/mm2), CD4+ cells (approximately 2 cells/mm2), and CD8+ cells (approximately 2.5 cells/mm2) were found in combination with low anticolloid antibody production (incidence of positive animals, 12.5%). The COD resulted in a normal thyroid function. The rats were euthyroid (range of T3, 1.6-1.2 nM/liter; T4, approximately 50 nM/liter; TSH, approximately 2 ng/ml) and had a normal thyroid weight (approximately 12.5 mg). However, some signs of thyroid autoimmune reactivity were found [number of intrathyroidal DC, approximately 40/mm2; approximately 3 CD4-positive (CD+) cells/mm2; approximately 3 CD8+ cells/mm2; together with a 30% incidence of anticolloid antibodies]. The LID and LID+ not only induced goiter formation [thyroid weight, 27.3 +/- 4.2 mg (mean +/- SD) after 12 weeks of LID and 38.4 +/- 5.3 mg after 4 weeks of LID+] and low production of T4 by the thyroid [28 +/- 3 nM/liter (mean +/- SD)] after 12 weeks of LID and 14 +/- 3 nM/liter after 2 weeks of LID+], but also induced various signs of thyroid autoimmune reactivity.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.In 1985 were reported the presence of immunoglobulins (Igs) blocking TSH-induced thyroid growth in the sera of about 50% of mothers giving birth to infants with sporadic congenital hypothyroidism (CH). Sera of the infants also contained the growth blocking Igs (1,2). These results suggested a trans¬ placental passage of maternal Igs influencing TSHinduced processes of thyroid growth which might be important in the pathogenesis of sporadic CH. Later Peters et al. (3) and recently Bogner et al. (4) also reported the presence of thyroid-reactive Igs in sera of CH children and their mothers; they de¬ scribed both growth blocking, in approximately 50% of maternal and infant sera, and thyroid cyto¬ toxic antibodies, in approximately 25% of maternal and infant sera. As early as in 1961 Balfour et al. (5) demonstrated an autoimmune involvement in CH.These authors discovered a new kind of thyroid autoantibodies directed towards a colloidal antigen, called 'second colloid antigen' (CA2). They showed in absorption and precipitation experi¬ ments that these antibodies were distinct from autoantibodies against the first colloidal antigen, thyroglobulin. CA2 antibodies were found in the sera of 4 out of 11 mothers of'athyreotic cretins' as well as in sera of patients with nowadays well estab¬ lished thyroid autoimmune disorders such as Ha¬ shimoto's thyroiditis (95-100%), atrophie thyroiditis (35-45%) and Graves' disease (40-50%).Since the initial report of Balfour et al., the antigen specificity and clinical relevance of CA2 antibodies have only scarcely been studied. Yet it has become clear that CA, antibodies are not pres¬ ent only in well-established thyroid autoimmune diseases but that they also occur in de Quervain's subacute thyroiditis. In this putatively viral disor-