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Thirty-five pregnant women with thyroid antibodies were followed during pregnancy and 12 month post partum. Twenty antibody-negative women served as controls and none of these developed postpartum thyroiditis in contrast to 12 of 35 antibody-positive women. Umbilical cord blood was collected at birth for measurements of thyroid antibodies, and blood samples for measurements of thyroid hormones were obtained at 5 and 30 days of age in the infants together with a clinical examination. There were no differences between the infants of antibody-positive and -negative mothers or the infants of those who developed postpartum thyroiditis with regard to gestational age at birth, birth weight, birth length or Apgar score, and no difference in thyroid function of the mothers and infants. However, serum TSH level was significantly higher in mothers who subsequently developed postpartum thyroiditis. Furthermore, a significantly lower growth during the first 30 days of life was observed in their infants. Our observations suggest a relationship between the maternal thyroid status in pregnancy and early growth in infancy.

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.

Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10(-1)-5.10(7) U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimic effects on thyroid cells afforded by recombinant interleukin 1 alpha and 1 beta. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1 beta-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.

The effects of human recombinant interleukin 1 alpha (20 pg/1-2 micrograms/l) and 1 beta (200 pg/1-20 micrograms/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1 beta (20 ng/1-20 micrograms/l), but not by interleukin 1 alpha. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

Sera from a reference pool, 29 controls and 18 patients with Graves' disease were fractionated on sepharose CL-4B protein A. After a primary elution of the unbound fraction at normal pH, IgG subclasses 1, 2 and 4 were eluted using a discontinuous pH gradient. The eluate was monitored by UV-absorption at 280 nm and three peaks were observed within narrow pH ranges in all sera tested. From the reference pool (n = 10) peak A was eluted at pH 6.6 +/- 0.1, peak B at 4.2 +/- 0.03 and peak C at 3.8 +/- 0.01. This distribution was partially related to the IgG subclasses with IgG1 recovered in peak C, while IgG2 and IgG4 were distributed in both peak B and C. Thyroid adenylate cyclase stimulating antibodies (TSAb) and thyrotrophin binding inhibiting immunoglobulins (TBII) were measured in the pooled fractions under these peaks. In the reference pool total assay variations (SD) were 10-22 per cent. The 95 percentiles of the 29 control values were used as reference range. In the 18 patients TSAb were positive in 4 in fraction A, 9 in B and 12 in C. TBII were found in one in fraction A, none in B and 13 in C. No correlation between TSAb and TBII values were found before or after fractionation. In most cases TSAb activity was highest in fraction C, however, in 3 patients fraction A was the more active and in these patients TBII were only found in fraction C. It is concluded, that the present results indicate a heterogeneity of the thyroid stimulating immunoglobulins with separation of the TSAb and TBII activities in some patients.

In the present study we have measured in parallel thyrotrophin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cylase stimulating immunoglobulins (TACSI) in patients with Graves' disease (GD) both before and during long-term antithyroid treatment. A statistical model based on the calculation of the differences (TACSI-TBII) is presented, comparing the changes in this parameter to the analytical variation. The correlation between TBII and TACSI in 52 patients with GD before treatment was: r = 0.58, P less than 0.0001. During long-term antithyroid treatment of GD the 2 activities changed in parallel in 39 of 45 patients followed. In a few patients discrepancies were observed, and 1 patient, initially TACSI positive, developed adenylate cyclase inhibiting IgG during treatment but without detectable TBII. In conclusion, 1) TBII and TACSI are significantly correlated in patients with GD both before and during long-term antithyroid treatment, 2) in some patients discrepancies between TBII and TACSI suggest, that these IgGs are heterogeneous with varying capacity for stimulation of the adenylate cyclase and receptor binding, and 3) adenylate cyclase inhibitory IgG without TBII activity was demonstrated in GD.

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.

Iodine metabolism and thyroid hormones in blood were studied in 19 men and 11 women who had been treated with thiazides for arterial hypertension from 1 month to 15 years. The results were compared with the findings from age-matched normal controls. No differences were found regarding 24-h 131I-thyroid uptake, thyroid iodide clearance, renal iodide clearance, plasma inorganic iodide, absolute iodine uptake (AIU), serum thyroxine (T4 (D)), resin T3 test (T3U) and TSH after TRH. Twenty-four-hour urinary iodine was higher in the patients treated with diuretics which could be explained by increased iodine intake. The findings of increased serum triiodothyronine (T3 (RIA)) and reverse T3 (rT3) might be due to changes in distribution volume in the thiazide-treated patients. Long-term treatment with thiazides in man do not lead to iodine depletion.

HLA typing of 86 patients with Graves' disease was performed for the A, B, C and D series antigens. An increased frequency of HLA-B8 (47 per cent) and Dw3 (51 per cent) compared with controls (23.7 and 21 per cent, respectively) was observed. The increase of B8 and Dw3 was almost exclusively found in a group of 48 patients with relapse of disease, whereas the frequency of B8 and Dw3 in patients without relapse did not differ significantly from that of the control group. No association with the presence of exophthalmos, thyroid antibodies, or antibodies to Yersinia enterocolitica serotype 3 could be found.

Nine consecutive patients with unilateral ophthalmopathy with suspected endocrine pathogenesis were investigated with a TRH test, a T3 suppression-test, thyroid autoantibodies and a subsequent computerized tomography (CT)-scan. All patients were clinically and biochemically euthyroid. Seven of 9 patients had a normal TRH test and 6 of 7 had a normal T3 suppression test. Slightly to moderately elevated microsomal and thyroglobulin (determined with radioimmunoassay) autoantibodies were found in 5 of 8 patients and in 1 patient thyroid stimulating immunoglobulins (TSI) were found. Three of the patients had normal thyroid function tests and no detectable thyroid autoantibodies. The subsequent CT-scan revealed that one of these had a maxillary tumour protruding into the orbita. The remaining 8 patients had enlargement of one (3 patients) or more (5 patients) eye muscles. Two of the 8 patients had bilaterally enlarged eye muscles, one of which was the patient with positive TSI. The remaining 6 patients had unilateral extraocular muscle enlargement. Thus, 2 of 9 patients had ophthalmopathy without thyroid dysfunction so-called isolated autoimmune ophthalmopathy or Graves' ophthalmopathy. Thyroid function tests seem to be of limited value in the diagnosis between endocrine and non-endocrine eye disease, and we recommend the use of diagnostic imaging (e.g. CT-scan) in patients with unilateral exophthalmus in order to diagnose malignant processes.

Measurement of serum thyroglobulin (Tg) and its autoantibody (TgAb) by radioimmunological methods was performed in 48 patients with Graves' disease during treatment with radioiodine (n = 16) or propylthiouracil (PTU) (n = 32). Twenty-five of the 48 patients were TgAb positive, their sera being inaccessible to measurement of serum Tg. TgAb showed only minor changes during PTU treatment, whereas TgAb fell rapidly after radioiodine, in 5 of 16 patients to unmeasurable levels, followed by a secondary rise to 4.5 times pre-treatment level after 20 weeks. Serum Tg showed a steady increase during the first weeks after radioiodine treatment, but fell to lower levels after one year. PTU caused only minor changes in the serum Tg concentration. There was no shift in molecular sizes of either Tg or TgAb during the course of the treatments. Five of 16 131I-treated patients developed myxoedema, 4 of whom were TgAb positive. Another 3 patients had high increases in TgAb without myxoedema. Six of 18 patients had relapse of thyrotoxicosis after withdrawal of PTU-treatment. There was no significant difference in serum concentrations of TgAb or Tg between those developing relapse and those remaining in remission, and it is concluded that serum Tg is a poor predictor of relapse in medically treated thyrotoxicosis.

Cultures of blood lymphocytes from 16 patients with Graves' disease (GD) and 14 matched controls were studied. Incorporation of [14C]thymidine was significantly increased in unstimulated cultures of GD lymphocytes, while the incorporation after stimulation with polyclonal activators (concanavalin A, pokeweed mitogen, phytohaemagglutinin), microbial antigens (E. coli, Candida albicans extract, purified protein derivative of tuberculin, Yersinia enterocolitica serotype 3) and subcellular fractions of human thyroid antigens did not differ from the controls. Due to the increased incorporation in unstimulated cultures, stimulation index is not suitable as an indicator of lymphocyte sensitization. After polyclonal activation or stimulation with thyroid antigens the lymphocytes were cultured for up to 21 days, and the supernatants were investigated for thyroid adenylate cyclase stimulating immunoglobulins (TACSI). No TACSI were demonstrated in supernatants of the lymphocyte cultures neither afer polyclonal activation nor after specific stimulation with several thyroid antigens.

In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 +/- 47 nmol/l (mean +/- SD) to 40 +/- 9 nmol/l after 6 weeks of PTU treatment and continued to be below the normal range during the next 4 months. In group 2 serum T4 decreased from 190 +/- 35 to 88 +/- 47 nmol/l and stayed in the normal range. Serum T3 was normalized in both groups after 6 weeks but increased to values above the normal range in group 1 after that time. In spite of unmeasurable TSH during the 6 months of treatment in group 1, thyroid volume, determined ultrasonically, increased significantly from 60 +/- 29 to 93 +/- 68 ml (P less than 0.05), but was unaltered in group 2 about 25 ml. Thyroid stimulating antibodies (TSAb) measured by adenylate cyclase activation (normal below 109%) decreased in group 2 from 117 +/- 23 to 90 +/- 17% (P less than 0.01) (6 months of therapy), but increased significantly in group 1, from 201 +/- 47% to a maximum value of 234 +/- 69% (P less than 0.05). TSH binding inhibitory immunoglobulins (TBII) (given as per cent inhibition, normal below 26%) decreased in group 2 from 43 +/- 29 to 29 +/- 27% (P less than 0.05) but were unaltered high in group 1, 66 +/- 25% before therapy and 57 +/- 26% after 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)