Hashimoto's encephalopathy (HE) is a rare autoimmune disease associated with Hashimoto's thyroiditis (HT). To identify the HE-related autoantigens, we developed a human brain proteome map using two-dimensional electrophoresis and applied it to the immuno-screening of brain proteins that react with autoantibodies in HE patients. After sequential MALDI-TOF-MASS analysis, immuno-positive spots of 48 kDa (pI 7.37.8) detected from HE patient sera were identi¢ed as a novel autoimmuno-antigen, K K-enolase, harboring several modi¢ca-tions. Speci¢c high reactivities against human K K-enolase were signi¢cant in HE patients with excellent corticosteroid sensitivity, whereas the patients with fair or poor sensitivity to the corticosteroid treatment showed less reactivities than cut-o¡ level. Although a few HT patients showed faint reactions to K K-enolase, 95% of HT patients, patients with other neurological disorders, and healthy subjects tested were all negative. These results suggest that the detection of anti-K K-enolase antibody is useful for de¢ning HE-related pathology, and this proteomic strategy is a powerful method for identifying autoantigens of various central nervous system diseases with unknown autoimmune etiologies. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
We show that HLA exerts a dual function, susceptibility and resistance, in controlling the development of GD and HT. We also show that the protective HLA allele is partially epistatic to the susceptible HLA allele in GD.
The duration of action of methimazole (MMI) was studied in patients with hyperthyroidism due to Graves' disease. Perchlorate discharge tests performed 24 h after MMI administration revealed greater than 10% discharge in 77% of 53 patients who received a single dose of 15 mg MMI and in 74% of 23 patients who received 30 mg. The mean percent discharges were 41.5 +/- 26.4% (+/- SD) and 35.4 +/- 28.0, respectively. Based on these results, hyperthyroidism was treated with a single daily dose (SDD) of 15 mg in 43 patients and with 30 mg in 32 patients, and the results were compared with retrospective analysis of 50 patients who were treated with divided doses of MMI (10 mg, 3 times daily). Within 12 weeks, 93% of the patients treated with 15 mg SDD, 91% treated with 30 mg SDD, and 86% treated with divided doses were euthyroid. The mean times to achieve euthyroidism in these patients were 5.3 +/- 3.6 (+/- SD), 5.3 +/- 3.1, and 5.6 +/- 3.0 weeks, respectively. Side-effects occurred in 2 patients treated with 15 mg SDD and in 6 treated with 30 mg SDD. We conclude that a single daily dose of 15 mg MMI is not only effective in most patients with Graves' hyperthyroidism, but also less frequently causes adverse effects.
Among hyperthyroid patients with thionamide-associated side effects, KI therapy was effective in two-thirds of cases, and about 40% of the patients experienced remission after KI therapy alone. The chance of remission was small among the patients refractory to KI.
Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH >10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen >7.1 mmol/l and creatinine >106 μmol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30(83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67–15591 μg/l, N=19) and a high thyroidal radioactive iodine uptake (51.5±29.3%at24h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.
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