Thyroid-Stimulating Immunoglobulin May Serve as Thyroid Eye Disease Biomarker

Serum thyroid-stimulating immunoglobulin (TSI) level is strongly associated with thyroid eye disease activity, according to research published in Eye (Lond). It may serve as a functional biomarker to identify patients with active disease in the clinic.

Researchers looked at 101 patients (mean age of 46 years, 70% women and 30% men). The investigators measured participants’ TSI level with a cell-based bioassay and evaluated the association between TSI and various demographic and clinical features of thyroid eye disease. They also determined a TSI cut-off value for discriminating active from inactive disease.

Researchers found a mean duration of ocular symptoms of 8 months (range, 1–60 months), and a mean TSI level of 402.7 SSR% (specimen-to-reference ratio percentage; range, 23–890). The prevalence of TSI-positive participants in this study with thyroid eye disease was 89%. 

The study found TSI levels are higher in men than in women (469.3 vs 374.6 SSR%; P =.023) and in smokers than nonsmokers (492.4 vs 369.9 SSR%; P =.004). They also note its inverse correlation with the duration of ocular symptoms (r=-0.295; P =.003), which is significantly different depending upon thyroid function (hyperthyroid, 439.5 SSR%; subclinical hyperthyroid, 397.8 SSR%; euthyroid, 251.3 SSR%; P =.003) and disease activity (active vs inactive, 488.3 vs 315.4 SSR%; P <.001) and severity (mild, 342.9 SSR%; moderate to severe, 446.6 SSR%; dysthyroid optic neuropathy, 566.6 SSR%; P <.001).

Using a multivariate regression analysis adjusting for other clinical characteristics, the investigators show that disease activity and thyroid function are significantly associated with TSI level (P =.010; P =.026, respectively). They also determined that the TSI cut-off value for predicting active disease is 406.7 SSR% (P <.001; area under the curve=0.847; sensitivity, 77.4%; specificity, 81.3%).

The primary limitations of the study included the retrospective, single-center design and the limited number of cases, especially patients with dysthyroid optic neuropathy.


Jeon H, Lee JY, Kim YJ, Lee MJ. Clinical relevance of thyroid-stimulating immunoglobulin as a biomarker of the activity of thyroid eye disease. Eye (Lond). Published online February 26, 2022. doi:10.1038/s41433-022-01981-z