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Objective: Graves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases. Aim: The aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms. Design: Serum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319COT, c.49AOG, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay. Results: Serum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, PZ0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, PZ0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31 [G] allele (genotype GGCGT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, PZ0.02). Also patients possessing CT60[G] allele (genotype GGCGA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, PZ0.03). Conclusions: It was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.

Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion. GH and insulin-like growth factor-I (IGF-I) exert anabolic activity in bones. Nevertheless, bone mineral density (BMD) loss is not uncommon in patients with acromegaly. It is assumed to be due to hypogonadism associated with the acromegaly. The aim of the study was to examine BMD at various skeletal sites and bone turnover and to assess the influence of impaired gonadal function and disease activity on BMD and turnover changes in acromegaly. A total of 62 patients were studied (40 women, 22 men). Among the women, 22 had active disease and 18 were cured; 16 women had normal gonadal function, and 24 were hypogonadal. Altogether, 12 men presented with active acromegaly, and 10 were cured; normal gonadal function was found in 10 men, and hypogonadism was diagnosed in 12 men. Controls were 30 healthy subjects. Densitometry using dual-energy X-ray absorptiometry of the lumbar spine, proximal femur, forearm, and total body was carried out. Bone turnover was studied based on serum osteocalcin, C-terminal collagen type 1 crosslinks, and bone alkaline phosphatase concentration. A disadvantageous effect of acromegaly on bone density was associated with hypogonadism in the distal radius (in women), the proximal femur (in men), and the total body (both sexes). An anabolic effect of GH during active acromegaly was present in the proximal femur only in men. We confirmed increased bone turnover in the presence of acromegaly, and these changes were similar regarding the activity of the disease and the gonadal status.

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