Endocrine Abstracts

Background: The concept of autoantibody-negative Graves’ disease (GD) is a subject of debate. Studies have revealed that autoantibody-negative GD does exist, albeit rare.1

Method: Over a 3-year period, a total of 108 hyperthyroid patients who exhibited diffuse or normal thyroid uptake on thyroid scintigraphy, were assessed in a cross-sectional study. The thyroid function tests, TSH-receptor antibody (TRAb) levels, anti-thyroid peroxidase (anti-TPO) antibody levels, and thyroid ultrasound scans of these subjects at initial diagnosis were reviewed. TRAb-seronegative GD was defined as the presence of hyperthyroidism with a negative TRAb and diffuse or normal thyroid uptake on thyroid scintigraphy. Continuous variables were compared using the Mann-Whitney U test, while categorical variables were compared using the Chi-Square test. Statistical significance was defined by a two-tailed p-value <0.05.

Results: The mean (SD) age of the study group was 58.59 (16.782) years with a female dominance of 66.67% (n=72). 83.3% (n=90) had overt hyperthyroidism whilst the remaining had subclinical hyperthyroidism. In the cohort with overt hyperthyroidism, 52.2% (n=47) had a positive TRAb status. In the cohort of patients with overt hyperthyroidism, thyroid-stimulating hormone (TSH) levels were significantly lower in TRAb-seropositive GD when compared to TRAb-seronegative GD (median TSH:0.008mIU/mL [IQR:0.008-0.011] vs median TSH:0.012mIU/mL [IQR:0.008-0.0285], respectively; P=0.0013). Furthermore, in the overt hyperthyroid cohort, free thyroxine (fT4) and free triiodothyronine (fT3) levels were significantly higher in TRAb-seropositive GD when compared to TRAb-seronegative GD (median fT4:34.1 pmol/L [IQR:25.1-46.85] vs median fT4:27.1 pmol/L [IQR:22.37-34.5], respectively; P=0.026 and median fT3:11.1 pmol/L [IQR:8.5-17.2] vs median fT3:8.1 pmol/L [IQR:6.6-10.8], respectively; P=0.001). Only 23.8% (n=5) of TRAb-seronegative GD had a positive anti-TPO antibody status when compared to TRAb-seropositive GD (P=0.0019). Age (P=0.242), gender (P=0.102), and presence of thyroid nodule/s (P=0.152) did not differ significantly between the overt TRAb-seropositive GD and TRAb-seronegative GD groups.

Conclusion: Our findings suggest that whilst TRAb-seropositive and TRAb-seronegative patients with Graves’ overt hyperthyroidism have comparable findings concerning age, gender, and thyroid nodule distribution, TRAb-seronegative GD is associated with a less severe form of biochemical thyrotoxicosis. In addition, our results indicate that TRAb-seronegative GD tends to be associated with negative anti-TPO antibody status.

References: 1. Paunkovic J, Paunkovic N. Does autoantibody-negative Graves’ disease exist? A second evaluation of the clinical diagnosis. Horm Metab Res. 2006;38(1):53-56