Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.

OBJECTIVE: To systematically examine the correlations between insulin resistance, plasma leptin concentration, obesity and the distribution of fat assessed by anthropometry and magnetic resonance imaging in Asian women. DESIGN: A cross sectional study of non-diabetic, normal weight women. SUBJECTS: Twenty-one healthy women aged 38.8 y (s.d. 11.7) and BMI 22.6 kgam 2 (s.d. 2.3). MEASUREMENTS: Intraperitoneal, retroperitoneal and subcutaneous abdominal fat volume was assessed by magnetic resonance imaging. Anthropometric data were collected. Total fat mass was assessed by bioelectric impedance analysis. Fasting serum lipids, insulin and plasma leptin were assayed. RESULTS: Generalized obesity correlated with subcutaneous abdominal fat mass (r 0.83, P`0.001), but not with intra-abdominal fat mass. Both intraperitoneal fat mass and retroperitoneal fat mass increased with age (r 0.58, P 0.005 and r 0.612, P 0.003, respectively). Abdominal subcutaneous fat mass was the most important determinant of insulin resistance and plasma leptin. Of the serum lipids, only fasting triglyceride correlated signi®cantly with the waist-to-hip ratio. CONCLUSIONS: It is possible that the large size of the subcutaneous depot compared to the intra-abdominal depot overwhelms any metabolic differences between adipose tissue from these two sites, resulting in the stronger correlation between insulin resistance and subcutaneous abdominal fat mass rather than intra-abdominal fat mass. On the other hand, the distribution of fat between subcutaneous fat depots may be important in the metabolic syndrome given the correlation of fasting triglyceride with waist to hip ratio but not with abdominal fat. However, the study population was small, younger and leaner compared to previous studies and we may not be able to generalize these results to all segments of the population. We con®rm that subcutaneous fat mass is the major determinant of plasma leptin.

OBJECTIVE: To study the relationship of leptin concentrations with indices of obesity, fasting insulin, insulin resistance and lipid pro®les (total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol and triglyceride) in an Asian cohort. DESIGN: Cross sectional study. SUBJECTS: A total of 133 healthy volunteers were enrolled (64 female: age: 25 ± 61 y, body mass index (BMI): 18.7 ± 45.1 kgam 2 and 69 male: age: 25 ± 61 y, BMI: 19.3 ± 35.0 kgam 2 ). MEASUREMENTS: Weight, height, waist and hip circumferences, blood pressure, lean body mass (by bioelectric impedence analysis (BIA)), plasma leptin and lipid pro®les were taken after a 10 h fast. RESULTS: Percentage of body fat measured by bioelectric impedance was the strongest determinant of plasma leptin (r 0.844, P`0.0001). Females had higher leptin concentrations than males for the same fat mass. In a multiple linear regression model, body fat percentage, (percentage body fat * gender), hip circumference and fasting insulin were signi®cant determinants of leptin concentration (r 0.882, P`0.0001). CONCLUSION: Leptin concentration correlated closely with percentage body fat in Asian subjects. Hip circumference as a corollary for peripheral obesity, was better associated with leptin than waist circumference or waist-to-hip ratio (WHR). Distribution of fat in females tended to be peripheral and may partly explain the gender difference. Fasting insulin level and central obesity were correlated with HDL-cholesterol, triglyceride and blood pressure, while fasting leptin had little correlation with these metabolic parameters. Therefore, insulin resistance was a better guide to cardiovascular risk assessment than plasma leptin.

The degree of hypothyroidism in agoitrous TSH-binding inhibitor immunoglobulins-positive patients appears to be more severe than that seen in other forms of AIT. The differences in thyroid stimulating blocking antiboby activity and response to LT4 therapy in agoitrous and goitrous autoimmune thyroiditis suggest that the TSH-binding inhibitor immunoglobulins in these patients are fundamentally different. The disappearance of TSH-binding inhibitor immunoglobulins in hypothyroid patients was not accompanied by the reversal of hypothyroidism in 50% of patients.

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