Graves' Disease
	Bogazzi et al., Pisa, Italy, compared the efficacy of controling hyperthyroidism when treated with lithium carbonate and radioiodine (RAI) as compared to RAI alone. Eighty-four patients with Graves' disease were randomly assigned to RAI, group A (n = 39) or RAI + lithium carbonate (900 mg/d for 6 days starting on the day after RAI) group B (n = 45). Follow-up was conducted until 12 months. Persistence of hyperthyroidism was observed in 25% of group A and 9% of group B. Hypothyroidism was 70% in group B and 46% in group A. The authors conclude that a short course of lithium carbonate potentiates the effects of RAI in Graves' disease. Brix et al., Odense, Denmark, investigated the genetic contribution to the etiology of Graves' disease in a population of Danish twins. In 18 monozygotic twins they found a probandwise concordance rate of 0.36 and in 33 pairs of dizygotic twins this rate was 0 (p = 0.012). The authors conclude that as the pairwise concordance rate is significantly higher in monozygotic pairs, that genetic factors in the etiology of Graves' disease are important. Recently an association has been found between Graves' disease or autoimmune hypothyroidism and polymorphism in the CTLA- 4 gene that plays a central role in T cell activation and downregulation. Donner et al., Frankfurt/Main, Germany, and Watermann et al., Sheffield and Cardiff, UK, found that polymorphism of this gene represents an additional risk marker for Graves' disease but also for autoimmune hypothyroidism and postpartum thyroid disease. Siegmund et al., Frankfurt/Main, Germany, also found that interferon-gamma polymorphism predisposes to development of Graves' disease. (Comment: Further studies are necessary to indicate if these and other genetic markers may be used to define subgroups that are at risk for development of autoimmune thyroid disease.) Inflammatory processes are often accompanied by increased serum levels of interleukin-6 (IL-6). These elevations have also been found in thyroiditis. Salvi et al., Parma, Italy, and Moncayo et al., Innsbruck, Austria, investigated the presence of IL-6 in patients with Graves' disease with or without thyroid associated ophthalmopathy (TAO). They found increased levels of IL-6 when TAO was present, whereas normal levels were found in patients with Graves' disease without TAO. It was also found that decreases in IL-6 were associated with clinical improvement of symptoms after steroid therapy or external orbital radiation. Glinoer et al., Brussels, Belgium, report a collaborative prospective investigation from 9 institutions in Belgium on the medical management of 140 newly diagnosed patients with a first episode of Graves' disease living in an area with marginally low iodine intake (50-75 µg/d). Patients were initially treated with a mean dose of 38 mg methimazole per day. Despite a 20% reduction in mean dosis after 2 months and co-administration of L-T4 in 63% of patients (mean dose 75 µg/d) free T4 was markedly reduced by 75% in average with 40% of cases below the lower normal limit. Also T3 was below normal in 34% of patients. After 4 months, despite a further reduction in MMI of 8% and all patients then receiving L-T4 substitution (mean 87 µg/d) free T4 and T3 were still below normal in 14 and 25% of cases respectively. Serum TSH rose >4mU/l in 25% of patients both at 2 and 4 months. The authors conclude that in an area of marginally low iodine intake, treatment of Graves' disease with MMI may rapidly induce frank elevations of serum TSH in a substantial number of patients. It is not known of this early rise in TSH will have an adverse effect on the longterm outcome of treatment.