The Combination of Absent Thyroid Peroxidase Antibodies and High Thyroid-Stimulating Immunoglobulin Levels in Graves' Disease Identifies a Group at Markedly Increased Risk of Ophthalmopathy

Abstract

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.

Prevalence and risk factors of thyroid-associated ophthalmopathy among Indians

“…Many study showed that thyroid binding inhibitor immunoglobulin or thyroid-stimulating antibody are involved in the etiology of TAO. [15][16][17] In present study, TBII levels were positive in most of TAO patients (96.25% and 90.0% in mild-moderate TAO and severe TAO respectively).…”

Detection of thyroid peroxidase mRNA and protein in orbital tissue

“…We hypothesized that these antibodies might modulate TRAb effects on GO (7). How TPOAb might affect the orbit is unknown and the presence of TPO at that site has not been previously described.…”

A Case of Hypothyroid Graves' Disease Following External Radiation Therapy to the Cervical Region

“…According to previous reports, titers of TSAb, but not of TBII, are significantly higher in patients with Graves' ophthalmopathy than in patients without Graves' ophthalmopathy [19], and the severity of Graves' ophthalmopathy is correlated with TSAb titers [9]. Although the absence of TPOAb is associated with a 5-fold increased risk of Graves' ophthalmopathy, the presence of TPOAb or TgAb is not a risk factor for Graves' ophthalmopathy [20]. These findings suggest that of the autoimmune antibodies detected in this case, TSAb is the most likely to be related to the development of Graves' ophthalmopathy.…”