431/879. The mechanism of spontaneous hypothyroidism in patients with Graves' disease after antithyroid drug treatment. The natural course of Graves' disease results in hypothyroidism in up to 20% of patients previously treated with antithyroid drugs. The precise mechanisms are not known, although autoimmune destruction of thyroid tissue has been proposed. We studied sequentially obtained serum samples from three patients with hyperthyroid Graves' disease previously treated with an antithyroid drug who became hypothyroid to determine possible causes of their hypothyroidism. Antithyroglobulin and antithyroid microsomal autoantibodies, TSH binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation-blocking activity were measured. autoantibodies were markedly elevated throughout the clinical course in all three patients. Patient 1 had no TBII and blocking activity and extremely high TSAb when she was euthyroid as well as hypothyroid. hypothyroidism was probably the result of autoimmune thyroid destruction. In patient 2, TSAb disappeared, and TBII and blocking activity increased markedly when she developed hypothyroidism, which thus appeared to result from blocking antibodies. Patient 3 had intermittent periods of hyper- and hypothyroidism before becoming and remaining euthyroid. While initially hypothyroid, TBII was weakly positive, and TSAb was strongly positive; subsequently, when hyperthyroidism recurred, TBII and TSAb were strongly positive. hypothyroidism appeared to result from focal autoimmune thyroiditis. patients with hyperthyroid Graves' disease may develop hypothyroidism later by different means. Autoimmune thyroiditis, diffuse or focal, with thyroid destruction is one mechanism. The appearance of antibodies that block TSH stimulation may be another. ( info) |
432/879. Immunohistochemical staining of normal and Graves' extraocular muscle. Extraocular muscle biopsies from normal individuals and five patients with Graves' ophthalmopathy were analyzed by immunohistochemical staining. fibroblasts in normal extraocular muscle as well as Graves' extraocular muscles expressed HLA-class II antigens, but the muscle cells did not. There was an increase of interstitial tissue in Graves' extraocular muscles but no visible damage to the muscle cells. In four of the biopsies from Graves' patients the cellular reaction was very weak. In the fifth patient the reaction was more pronounced with macrophages predominating, but with few lymphocytes and almost equal amounts of B and T cells. We could not confirm the earlier described specific extraocular muscle antibodies in sera from Graves' patients and conclude that there seems to be an activation of orbital fibroblasts in Graves' ophthalmopathy. This may contribute to the pathogenesis of the disease. ( info) |
433/879. A patient with Graves' disease who developed hypothyroidism associated with thyroid stimulation blocking immunoglobulin during anti-thyroid drug therapy. A girl, 12 years of age, developed Graves' disease compounded with rheumatic fever and idiopathic thrombocytopenic purpura. thrombocytopenia improved under short-term treatment with steroids and her mitral valvular insufficiency, due to the rheumatic fever, disappeared 4 years later. Initially, she had been treated with propylthiouracil (PTU) for 28 months. She suffered a relapse 9 months after stopping PTU and so she was given further PTU therapy. However, hypothyroidism developed 11 months after the initiation of therapy and continued, though further PTU treatment was discontinued. She now receives 1-thyroxine and maintains a euthyroid state. At the onset of the patient's hyperthyroidism, the TSH-binding inhibitor immunoglobulin (TBII) and the thyroid stimulating antibodies (TSAb) were found to be positive. During the remission period, only the thyroid stimulation blocking immunoglobulin (TSBI) was weakly positive. At relapse, only TBII was mildly positive. When hypothyroidism developed, both TBII and TSBI were positive, and TSAb was negative in all testings of her diluted IgGs. The patient's TBII and thyroid dysfunction were unaffected by high-dose intravenous gammaglobulin therapy or by treatment with prednisolone 0.5 mg/kg/day for 2 weeks. In conclusion, the emergence of TSBI during or after anti-thyroid drug therapy might possibly lead to hypothyroidism in patients with Graves' disease. ( info) |
| Chronic lymphocytic thyroiditis (Hashimoto's disease) is usually regarded as a stable and irreversible condition. This report describes a patient with autoimmune hypothyroidism who subsequently developed hyperthyroid Graves' disease. patients with Hashimoto's thyroiditis should be followed regularly, and the development of clinical and/or biochemical hyperthyroidism should alert the physician to the possibility of another thyroid disease. ( info) |
435/879. Anti-bovine TSH antibodies in patients with Graves' disease and primary myxedema. Three patients with Graves' disease and one patients with primary myxedema had serum TSH-binding immunoglobulins of high affinity detected by the TSH binding inhibition immunoglobulin (TBII) assay. These IgGs bound 61%, 33%, 60% and 53% of radiolabeled TSH, respectively, higher than the maximal specific binding (25%) in the TBII assay. Such binding was detected even in the absence of TSH receptor with only small differences in the precipitable radioactivity (61%, 28%, 61%, 54%, respectively, in comparison with the assay non-specific binding 11.3%). The 125I-bTSH binding of IgGs was competitively inhibited by the addition of bTSH, but not inhibited by hTSH. Moreover IgG binding to bTSH was not inhibited by the addition of serial dilutions of TBII positive pooled Graves' IgG (0.1-10 mg/ml) from different untreated patients. The titers of these TSH binding antibodies were not changed during the treatment of Graves' disease. Following guinea pig fat cell membrane receptor purification, the IgG of one patient with Graves' disease revealed TBII activity of 43.7% inhibition of 125I-bTSH binding to the TSH receptor without binding activity of 125I-bTSH in the absence of the TSH receptor. These studies suggest that anti-TSH antibodies and TSH receptor antibodies are present independent of one another in sera of some patients with autoimmune thyroid diseases and anti-TSH antibodies result in false TBII assay results. ( info) |
436/879. Graves' disease in a patient with thyroid hemiagenesis. A case is presented of Graves' disease occurring in a patient with hemiagenesis of the thyroid gland. The diagnosis was suspected clinically and was confirmed by laboratory tests and imaging studies, as well as by the presence of thyroid-stimulating antibody. ( info) |
437/879. Orbital decompression for Grave's disease leaving the periosteum intact. A prospective trial was carried out to determine whether or not transorbital floor and medial wall decompression without opening the orbital periosteum would relieve compressive optic neuropathy in patients with Grave's disease. In four orbits (three patients), the procedure was performed, and in all cases, the vision returned to 20/30 or better. All other parameters of optic nerve function improved as well. No patient had worsening of ocular motility that was attributable to the surgery. The amount of retroplacement of the globe may be less than with standard orbital decompression. ( info) |
438/879. Thyroid antigen-mediated glomerulonephritis in Graves' disease. We describe a patient with Graves' disease in whom marked proteinuria, microhematuria and hypoalbuminemia were associated. Renal biopsy demonstrated electrondense deposits in the capillary basement membrane, a finding consistent with immune complex glomerulonephritis. Indirect immunofluorescent examination with rabbit antihuman thyroglobulin indicated that these electron-dense deposits were thyroid antigen-mediated immune complexes. ( info) |
439/879. Graves' hyperthyroidism following primary hypothyroidism: sequential changes in various activities of thyrotropin receptor antibodies. A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal less than 38%) and [3H]thymidine incorporation (99.5%, normal less than 40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal less than 15%) of TSH binding inhibitor immunoglobulin. When he developed hyperthyroidism and goitre, his IgG showed a strong thyroid stimulation, both cAMP production (27-fold increase) and [3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies. ( info) |
440/879. Improvement of infiltrative ophthalmopathy in parallel with decrease of thyroid-stimulating antibody (TSAb) activity in two patients with hypothyroid Graves' disease. Two patients with primary hypothyroidism associated with infiltrative ophthalmopathy without previous history of hyperthyroidism are presented. Anti-TSH receptor antibodies (TRAb) were detected by radioreceptor assay (TBII), and unexpectedly their biological activity was not of a blocking (TSBAb), but of a thyroid-stimulating type (TSAb). After the initiation of levothyroxine therapy, the TBII and TSAb activities both decreased gradually with normalization of the elevated TSH level. The inflammatory eye signs improved strikingly in parallel with decrease of these antibody activities. These data indicate that (1) TRAb in primary hypothyroidism do not always show TSAb activity, (2) the decrease in TRAb following levothyroxine therapy in these patients appeared to correlate with suppression of TSH, (3) changes in infiltrative ophthalmopathy were associated with that of TSAb even in primary hypothyroidism, and (4) the hypothyroidism in these patients is justifiably diagnosed as "hypothyroid Graves' disease". TSAb might be somewhat related to the pathogenesis of ophthalmopathy in autoimmune thyroid diseases. ( info) |