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Predicting the Development of Orbitopathy in Graves Thyroidopathy Patients: The Potential Role of TSI Testing

Takakura, Ako M.D., M.P.H.*; Kirkeby, Kjersti M.D.; Earle, Karen M.D.; Silkiss, Rona Z. M.D., F.A.C.S.*

Ophthalmic Plastic and Reconstructive Surgery: September/October 2015 - Volume 31 - Issue 5 - p 369–372
doi: 10.1097/IOP.0000000000000350
Original Investigations

Objective: To determine whether thyroid-stimulating immunoglobulin (TSI) testing can predict the risk of development of Graves orbitopathy in newly diagnosed Graves thyroidopathy patients.

Design: Retrospective cohort, from 2008 to 2013.

Setting: The Thyroid Referral Center at California Pacific Medical Center.

Participants: A retrospective cohort of newly diagnosed Graves thyroidopathy patients from the California Pacific Medical Center Thyroid Referral Center. Patients were included if they had TSIs drawn at or near the time of diagnosis of Graves thyroidopathy. Patients were excluded from the study if they had a long-standing diagnosis of Graves thyroidopathy, orbitopathy at time of diagnosis, no TSIs drawn, or follow up of less than 6 months.

Main Outcome Measures: Patients were followed for the development of orbitopathy as determined by their endocrinologists. Results were adjusted for family history, smoking status, age, radioiodine ablation treatment, and race.

Results: Thirty-three patients met inclusion criteria out of a screened population of 506 patients. Eight out of 33 patients (24%) developed orbitopathy. The mean time from diagnosis of Graves’ thyroidopathy to development of orbitopathy was 11.6 months (median: 7.5 months, range: 1 to 20 months). The mean initial TSI value was 421.3 in those that developed orbitopathy compared to 245.9 in those who had at least 6 months of documented follow-up and did not develop orbitopathy (p = 0.04). Those in the top tercile of initial TSI values were 14 times as likely to develop orbitopathy (relative risk (RR) = 14.0, p = 0.02; multivariate adjusted RR = 13.08, p = 0.03). Family history, smoking status, age, radioiodine ablation, thyroid-stimulating hormone, and race were not statistically significant predictors.

Conclusions: TSI level greater than 400 at time of presentation of Graves thyroidopathy may be a useful predictor of risk for development of orbitopathy. This information will help to identify patients likely to benefit from early referral to an ophthalmologist for possible preemptive therapy to prevent the development of orbitopathy. Prospective cohort studies are needed to definitively establish the metrics for TSI as a predictor of orbitopathy.

Thyroid-stimulating immunoglobulin (TSI) may be a useful predictive risk factor for development of orbitopathy in patients newly diagnosed with Graves thyroidopathy.

*Department of Ophthalmology, California Pacific Medical Center, San Francisco, California; and Department of Endocrinology, California Pacific Medical Center, San Francisco, California, U.S.A.

Accepted for publication September 30, 2014.

The authors have no financial or conflicts of interest to disclose.

Address correspondence and reprint requests to Ako Takakura, M.D., M.P.H., Department of Ophthalmology, California Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115. E-mail:

© 2015 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.