To evaluate the extent and clinical relevance of epitope heterogeneity for stimulating TSH receptor antibodies (TSHRAbs), we measured the activity of IgG preparations from 66 untreated patients with Graves' disease using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR and two TSHR chimeras with residues 9-165 (Mc1 + 2) or 90-165 (Mc2) substituted by equivalent residues of the LH/CG receptor. IgG from 68% of patients lose all of the stimulating TSHRAb activity with the chimeras; IgG from 27% lose most of the activity. Thus, we show that 95% of patients have stimulating TSHRAbs that require epitopes on the N-terminal portion of the extracellular domain of the TSHR and demonstrate the importance of epitopes within residues 90-165 for the first time. Heterogeneous epitope distribution, residual activity with one or both chimeras, i.e. with epitopes other than on the N-terminus of the TSHR, occurred in 21 patients (group A). Forty-five patients with homogeneous epitope distribution (group B) had stimulating TSHRAbs that depended only on epitopes on the N-terminus of the TSHR. Patients in group A were more likely to become euthyroid during antithyroid drug therapy and to do so more quickly than group B patients. The CHO-human TSHR cell system described herein appears to be as effective as the FRTL-5 rat thyroid system in stimulating TSHRAb detection; however, the two systems appear to measure different antibody populations in about 30% of cases. Further, stimulating TSHRAb activities measured in the FRTL-5 system tend to correlate better with goiter size and 99mTc pertechnetate uptake, whereas stimulating activities measured in the CHO-human TSHR/chimera system correlate better with free T4 and T3 levels.

An epidemiological study on diabetic ketoacidosis (DKA) was done by analysis of 207 cases collected from the medical records of 6 major general hospitals in Seoul area during the period of 5 years between 1979 and 1984. There was female predominance in the occurrence of DKA (male/female ratio, 0.71) in spite of the male predominance in general prevalence of diabetes mellitus (1.80). This female predominance in DKA was most striking in the age group under 40. There was a significant seasonal variation in the occurrence of DKA. DKA occurred most frequently in colder season with the highest peak in December. In July and August, the hottest season in Korea, not even a single case of DKA was recorded in this series. No discernible precipitating factor was found in 39.3% of DKA cases and infections was present as a cause of DKA in 30% of cases. In 27.5%, DKA was the first clinical presentation of diabetes and in the remainders of cases, diabetes was known to be present for average of 6.4 years. Mortality of DKA was 13.2% in this series. As to the socioeconomic status, the education level, the style of living and the duration of diabetes, there were not ascertainable differences between the DKA cases and other diabetic cases. The prospective epidemiological study of diabetic population in Korea, especially in female group, would be necessary for elucidation of the characteristics of DKA in Koreans such as the female predominance and the seasonal difference of the occurrence.

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