Hyperthyroidism
	Anti-endothelial cell antibodies (AECA) are found in systemic autoimmune diseases and have been shown to release endothelin-1 (ET-1) from human cultured endothelial cells in vitro, suggesting endothelium injury. Centanni et al., Roma, Italy, investigated the presence of AECA and ET-1 in 21 euthyroid controls, 12 hypothyroid patients (3 TPOAb positive), 13 hyperthyroid subjects (8 TPOAb positive). Serum ET-1 and AECA levels were not different in hypothyroids as compared to controls. In hyperthyroid subjects, however, both ET-1 and AECA levels were increased. When subjectes were divided in TPOAb positive and negative, both parameters were increased in the former group. Aizawa et al., Sendai, Japan, studied 260 patients with Graves' disease treated with radioactive iodine-131 between 1 to 15 years earlier. Twenty-eight patients were permanent hypothyroid, 39 patients had transient hypothyroidism, 83 patients were euthyroid without transient hypothyroidism, and 110 patients were still hyperthyroid. The mean estimated time between therapy and development of permanent hypothyroidism was 96 months. (Comment: The lesson of this study is that a substantial number of patients developed transient hypothyroidism. This should be kept in mind to avoid unnecessary T4 substitution in these patients.) Frigato et al., Mestre-Venezia, Italy, routinely counted white blood cells 15, 30, and 60 days after starting 20-30 mg methimazole for Graves' disease in 1152 patients. Severe leucopenia (leucocyte count between 1500-500/µL) was seen in 3 patients and less than 500/µL in 1 patient. At the time of detection none of these patients had any symptoms and methimazole was withdrawn, after which leucocyte count normalized in about 2 weeks. The authors conclude that, despite this low number of patients developing leucopenia, routine monitoring of blood cell count could prevent this life- threatening complication as apparently a non-symptomatic period preceeds clinical symptoms. (Comment: In most thyroid clinics routine leucocyte count is not done because of low cost-effectiveness. I am not sure that the here reported results will change this policy.) Moncayo et al., Innsbruck, Austria, measured tumor necrosis factor (TNF), neopterin (these parameters reflect macrophage activation), and soluble IL-2 receptor (sIL-2R) (this parameter reflects lymphocyte activation) in 60 patients with Graves' disease of whom 38 had TAO, 30 patients with toxic nodular goiter, and in 40 controls. This study was done in order to evaluate if these parameters could distinguish between immune and non-immune hyperthyroidism. Neither neopterin nor TNF allowed this discrimination, as surprisingly neopterin was normal in Graves' disease, but elevated in toxic nodular goiter. However, sIL-2R was elevated in the whole group of patients with Graves' disease, but normal when associated with TAO. In addition a significant correlation between FT4 and sIL-2R was present only in the patients with Graves' disease. The authors conclude that lymphocyte activation as reflected by increased levels of sIL-2R is characteristic of patients with Graves' disease without TAD. (Comment: It is puzzeling why sIL-2R is not elevated in GD, when TAO is present.) A rare cause of hyperthyroidism is that called familial non-autoimmune hyperthyroidism. Five cases have already been reported in the literature and Führer et al., Leipzig, Germany, reported another case of this entity in a mother and her 9 year old son. The disease is caused by a mutation in the TSHR gene and in this case a shift from leucine to phenylalanine was found at residue 629 in the gene (new found mutation). As this disease is autosomal dominant, the authors stress genetic counselling in these cases because there is a 50% risk of transmitting the affected gene to the offspring. (Comment: Although the disease is rare, one should think of it, especially in cases with familial hyperthyroidism when patients have a diffuse goiter, no TAO, and no circulating thyroid antibodies. In these cases aggressive ablative treatment is necessary since relapse occurs after medical treatment or when a thyroid residue remains after thyroid ablation.) Nystr”m et al., G”teborg, Sweden, analyzed body composition by CT-scanning in 4 men and 6 women before as well as 3 and 12 months after treatment by thyroidectomy or radioiodine for hyperthyroidism. If necessary supplementation with T4 was given. All subjects increased in body weight with a mean value of 3.1 kg after 3 months, and 7.7 kg after 1 year. The increase in body weight after 3 months was only explained by an increase in muscle tissue. No change in adipose tissue was detected at this time. After 12 months a significant increase in visceral and subcutaneous adipose tissue was present, but no further increase in muscle tissue occurred. Visceral organ sizes did not change.