A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells.

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.

Evaluation of the fructosamine test in obesity: consequences for the assessment of past glycemic control in diabetes.

The effect of obesity in diabetic and nondiabetic states on serum fructosamine levels, as measured by the nitro blue tetrazolium reduction method, was investigated. In 26 nondiabetic obese subjects, the mean (SD) fructosamine (1.78 +/- 0.16 mmol/L) and protein corrected fructosamine concentrations (25.7 +/- 2.5 mumol/g) were significantly lower than in nondiabetic lean control subjects (2.06 +/- 0.18 mmol/L and 30.5 +/- 2.5 mumol/g, respectively; p less than 0.01). Hemoglobin A1C, blood glucose and serum protein concentrations were normal in obese subjects. Interference from hypertriglyceridemia, hemolysis, or drugs was excluded. In diabetic subjects, fructosamine correlated with hemoglobin A1C, but the least-squares regression lines were different in 16 nonobese and in 19 obese patients, so that for the same hemoglobin A1C value, fructosamine level was 16% lower in obese compared to nonobese diabetic subjects. In vitro studies showed a significant decrease in 14C-glucose incorporation in serum proteins of obese nondiabetic subjects compared to control subjects. Similarly, the rate of formation of fructosamine in sera of obese nondiabetic subjects incubated with 12 mmol/L and 30 mmol/L glucose concentrations was slower than in sera of control subjects. In conclusion, fructosamine is underestimated in obesity, both in diabetic and nondiabetic patients, and its validity as an index of glycemic control may be impaired in obese subjects. This decrease is due to an alteration in the glycation process itself.