During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency. To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies, we have investigated the thyroid volume, thyroid function, urinary iodine excretion and antibodies to thyroid peroxidase at 10-12 weeks of gestation and postpartum in 38 mothers receiving 300 micrograms potassium iodide/day and in 70 mothers without iodine supplementation. In all of their newborns thyroid volume was determined by ultrasound. The thyrotropin (TSH) levels and antibodies to thyroid peroxidase (TPO-ab) in the neonates were measured in dried blood spots on filter paper from their newborn screening. Urinary iodine excretion was increased significantly after iodine supplementation in mothers (p < 0.001) and their newborns (< 0.05). No hypo- or hyperthyroidism was observed in the mothers or newborns. Interestingly, no difference of maternal thyroid volumes was observed between the two groups after pregnancy, but the volumes of the thyroid glands in newborns of mothers who received iodine were significantly (p < 0.004) lower (0.7 +/- 0.4 ml) than in the control group (1.5 +/- 1.1 ml). There was no change in the frequency of TPO-ab in either group after pregnancy. In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn. This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab.

Abstract. Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were prospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P< 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P=0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P= 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P=0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq 131iodine vs. an activity calculated to deliver 100 Gy for treatment of Graves' thyrotoxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radioiodine application (range 4.5-8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for both approaches, but only in retrospective investigations. Investigated prospectively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic success was inversely related to thyroid size. The rate was 100% for thyroid volumes < or = 15 mL, 95% for 16-30 mL, 68% for 31-45 mL, 44% for 46-50 mL, 20% for 61-75 mL and 25% for > or = 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume < or = 15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11% for a target dose of 50 Gy, 50% for 100 Gy, 67% for 150 Gy, 80% for 200 Gy, 84% for 250 Gy, 88% for 300 Gy, 90% for 350 Gy and 93% for 400 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)

In this paper, we report the results of a randomized prospective study on radioiodine treatment in patients with Graves' hyperthyroidism. Complete data were obtained in group 1 from 98 patients 6 months after application of a standard activity of 15 mCi (555 MBq) of 131I and in group 2 from 107 patients who received a target dose of 100 Gy. In group 1, the overall success rate was 71%, but the results in the subgroups clearly were related inversely to the thyroid volume, ranging from 100% in patients with a thyroid volume < 15 mL to about 20% in those with a thyroid size of > 60 mL. In contrast, patients who received a target of 100 Gy showed very similar results, with success rates of about 40-50% in all but one subgroup. Only patients with a thyroid volume < 15 mL had a success rate of about 80%. But due to an incidental increase of uptake and/or effective half-time from the test to the therapy activity, this subgroup received a target dose of about 160 Gy. Additional calculation of the actual target dose in group 1 (standard activity) showed that, with a dose of 200 Gy, a success rate of 80% was obtained. Also, the thyroid volume reduction was related inversely to the target dose. Because the literature is abundant, only a restricted number of references are discussed that are either in agreement with our results or in sharp contrast to them. The reason for these discrepant results might be the difference in the scheme of pretreatment or the different alimentary iodine supply between, for example, Great Britain and the United States on the one hand and Germany on the the other hand.

Antibody-dependent cell-mediated cytotoxicity (ADCC) against human thyroid cell targets was measured in a chromium release assay, using serum from patients with autoimmune thyroid diseases. The source of effector cells was peripheral blood mononuclear cells from normal subjects. Mean (+/- SD) specific lysis produced by serum from patients with Hashimoto's thyroiditis was 27.3 +/- 6.1%, compared to 10.6 +/- 4.7% produced by serum from normal subjects and 13.3 +/- 10% using serum from patients with Graves' hyperthyroidism. Cytotoxicity using serum from hyperthyroid patients was not different after treatment. Thyroid cell targets from histologically different thyroid cell preparations (Graves' disease, multinodular goiter, normal thyroid) were equally sensitive to killing, although cells from a benign thyroid adenoma were much less sensitive. A strong positive correlation was found between percent specific lysis and titers of serum microsomal antibody. By addition of patients' immunoglobulin to normal serum, we found that microsomal antibodies were responsible for the cytotoxic effect, whereas thyroglobulin antibodies did not mediate cytotoxicity. These results demonstrate that ADCC plays an important role in the thyroid cell destruction of chronic (Hashimoto's) thyroiditis. Although cytotoxic activity was associated with the antimicrosomal-, but not antithyroglobulin-, positive immunoglobulin G fraction, it is not clear whether the microsomal antibody itself, or an unidentified antibody occurring in the same antibody fraction, is the mediator of cytotoxicity in this disorder.