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Intravenous Gammaglobulin in a Hypothyroid Patient with the Antiphospholipid Antibody Syndrome

TO THE EDITOR: Many reports of thrombocytopenia associated with autoimmune thyroid disease have occurred since Jackson's first description [1]. Most were cases of autoimmune thyroid disease complicated by idiopathic thrombocytopenic purpura. We describe a hypothyroid patient with thrombocytopenia and a paradoxical thromboembolic episode, diagnosed as having an antiphospholipid antibody syndrome because of high serum levels of anticardiolipin antibodies and lupus anticoagulant. A 65-year-old Japanese woman was admitted to our hospital with a goiter and signs and symptoms of hypothyroidism. At 53 years of age, she had had a cerebral infarction. Laboratory data confirmed hypothyroidism as follows: The free-triiodothyronine value was 1.69 pmol/L; the free-thyroxine value was 0.9 pmol/L; the thyroid-stimulating hormone value was 147.7 mU/mL; titers of antimicrosome antibody and of antithyroglobulin antibody were high; Iodine-123-thyroid uptake was 8.2%; and the thyroid-stimulating hormone receptor antibody value was 0.7%. Although the patient's platelet count was 1.9 104/mm3, she had never shown signs of a bleeding tendency. Bone marrow showed almost normal megakaryocyte, red blood cell, and leukocyte findings. The antiplatelet antibody test was positive, and the platelet-associated IgG level was as high as 493.2 ng/107 cells. The test for lupus anticoagulant was positive, and anticardiolipin antibody levels were remarkably high at 4.2 for IgG and 2.1 for IgM (normal 1.0 for both). Because thyroxine replacement therapy did not change either the platelet count or the anticardiolipin antibody levels, we used intravenous gammaglobulin infusions. The platelet count increased to 5.0 104/mm3 after 100 g of gammaglobulin was administered (20 g for 5 d) and remained the same 6 months later. Anticardiolipin antibody IgG and IgM levels, as well as platelet-associated IgG levels, tended to decrease gradually after gammaglobulin therapy was discontinued (Figure 1). Figure 1. Changes in platelet count and in thyroid hormone, thyroid-stimulating hormone autoantibody, and anticardiolipin antibody levels throughout therapy. Gammaglobulin infusions have been effective in treating immune complex-related disorders, but changes in anticardiolipin antibody level have seldom been reported. In one case [2], levels of anticardiolipin antibody decreased slightly with gammaglobulin infusions. In our patient, infusion resulted in an increased platelet count and decreased levels of anticardiolipin antibodies; these results were documented again 6 months later. Thyroid autoantibodies decreased markedly after thyroxine replacement and even further after gammaglobulin infusion. Patients with Hashimoto thyroiditis who were treated with gammaglobulin have shown decreased levels of thyroid autoantibodies and increased serum thyroid hormones [3]. Our experience suggests that anticardiolipin antibodies may be a factor in inducing the thrombocytopenia observed in autoimmune thyroid disease. A recent report [4] in which anticardiolipin-antibody IgG was significantly higher in hyperthyroidism than in euthyroidism supports this hypothesis.