Can We Predict Thyroid Eye Disease Occurrence and Progression in Newly Diagnosed Graves’ Disease?

Clinical Thyroidology®Vol. 35, No. 1 HyperthyroidismFree AccessCan We Predict Thyroid Eye Disease Occurrence and Progression in Newly Diagnosed Graves’ Disease?Kharisa N. Rachmasari and Omar El KawkgiKharisa N. Rachmasari Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Mayo Clinic Rochester, Minnesota, U.S.A.Search for more papers by this author and Omar El Kawkgi Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Mayo Clinic Rochester, Minnesota, U.S.A. Department of Endocrinology, Mayo Clinic Health System, Eau Claire, Wisconsin, U.S.A.Search for more papers by this authorPublished Online:17 Jan 2023https://doi.org/10.1089/ct.2023;35.9-11AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of:Ahn HY, Lee J, Lee JK 2022 Predictive model for Graves' ophthalmopathy in patients with new-onset Graves' disease. Thyroid. Epub 2022 Nov 9. PMID: 36128837.SUMMARYBackgroundGraves’ ophthalmopathy, better known as thyroid eye disease (TED), occurs in about 25% of patients with Graves’ disease, and it can cause pain, disfigurement, and debilitation (1). Symptoms manifest in a wide spectrum, from dry eyes, to foreign-body sensation, to sight-threatening optic neuropathy (2). Identifying risk factors for the development of TED among patients with Graves’ disease is important in helping to counsel patients, determine treatment options, and clinically monitor for its progression. The aim of this study (3) was to assess risk factors that would predict development and progression of TED in patients with newly diagnosed Graves’ disease and to construct a clinical predictive model.MethodsThis was a retrospective study of patients who were diagnosed with new-onset Graves’ disease between January 2011 and June 2021 at Chung-Ang University Hospital, South Korea. Subjects with missing dates of Graves’ disease or TED diagnosis, diagnosis of TED prior to Graves’ disease diagnosis, or preexisting Graves’ disease were excluded. A total of 1074 patients were included; this group was divided into a derivation cohort (n = 853 between 2011 and 2017) and a validation cohort (n = 221 between 2018 and 2021). Demographic characteristics, time of diagnosis of Graves’ disease and TED, remission, duration of treatment with antithyroid medications, history of thyroid surgery or RAI treatment for Graves’ disease, activity and severity of TED, and laboratory results at baseline were analyzed. A multivariable logistic-regression model was constructed from the derivation cohort to determine risk factors associated with the occurrence of TED. A predictive model was developed based on this and was tested on the validation cohort.ResultsIn the derivation cohort, 101 patients (11.8%) developed TED. Patients who were smokers, were younger at the time of Graves’ disease diagnosis (35 years vs. 42 years), had a first-degree family history of Graves’ disease, or had higher levels of serum thyrotropin-binding inhibitor immunoglobulin (TBII) were more likely to develop TED. Of 101 patients with TED, those with active and moderate-to-severe disease were excluded, leaving 93 to be analyzed. Progressed to active or moderate-to-severe TED occurred in 11 patients who had inactive or mild TED. Patients who were older than 45 years at time of Graves’ disease diagnosis or who had different distributions of the components in the initial clinical activity scores (CAS) were more likely to have TED progression.On multivariable logistic-regression analysis, female sex (odds ratio [OR], 2.23), active smoking (OR, 5.96), age at Graves’ disease onset (OR, 0.98), first-degree family history of Graves’ disease (OR, 1.59), total cholesterol level (OR, 1.01), and TBII level (OR, 1.28) were predictive for the development of TED. In addition, age > 45 years at Graves’ disease diagnosis (OR, 3.42) and high initial CAS (OR, 10.74) were independent predictors for TED progression. The predictive model for TED occurrence had an area under the curve of 0.71 in the derivation cohort and 0.71 in the validation cohort.ConclusionsThe following factors were predictive for TED: new-onset Graves’ disease, female sex, smoking, young age, first-degree family history of Graves’ disease, high cholesterol level, and high TBII level. Age >45 years at diagnosis was a predictor of TED progression.COMMENTARYThis study supports findings from other studies examining risk factors for the development of TED among patients with Graves’ disease. Interestingly, however, unlike in previous studies, RAI treatment was not found to be a significant risk factor in the development of TED (4,5). This is probably due to the small number of patients who underwent RAI treatment in this cohort and steroid use around the time of RAI treatment. In contrast, smoking, for example, has been consistently shown to be a significant risk factor for the development or worsening of TED (3,5,6), as was also shown in the current study.This predictive model may be helpful in guiding patient counseling and in treatment decision-making. Those who are at higher risk might benefit from shorter follow-up intervals with focused eye exams and a lower threshold for referral to an ophthalmologist or possibly consideration of glucocorticoid or monoclonal antibody treatment.Furthermore, this model's application is most useful in the context of modifiable risk factors. Thus far, based on these data, smoking status is the only modifiable risk factor for TED. Using this tool with patients who smoke may help to guide motivational interviewing and counseling. In practice, we think the proposed nomogram is probably easier to use and visualize, compared to the PREDIGO model, which provides a scoring system with a cutoff value (6). In addition to smoking, the serum cholesterol level was found to be another potentially modifiable risk factor for TED development (7). At this point, it is still unclear whether current evidence would recommend statin use for elevated cholesterol levels in patients with Graves’ disease (8). Studies have mostly been limited by their retrospective designs, and a clinical trial would be needed to investigate the role of statins as preventive treatment for TED.This study, however, has some limitations because of its retrospective design and lack of external validation. To better assess its generalizability, external validation in other cohorts is needed, particularly in the context of cohorts with a higher use of RAI. Additionally, prospective data to measure the changes in TED outcomes with modification of the identified risk factors would be a necessary future step. For example, does starting a statin change TED risk? How much does quitting smoking modify risk? Furthermore, with the introduction of various monoclonal antibody treatments, such as teprotumumab and other more targeted experimental agents, it would be interesting to assess the role these agents may play in altering risk profile and progression prediction.Overall, the proposed model is most useful in patients with a new or recent diagnosis of Graves’ disease and who have modifiable risk factors and is another potential tool to help guide clinicians and patients in understanding the risk of TED. External validation is still needed, but this is a step toward more precise risk assessment of TED in patients with new-onset Graves’ disease.Disclosures: The authors have no relevant conflicts of interest to declare.References1. Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML 2020 Epidemiology, natural history, risk factors, and prevention of Graves' orbitopathy. Front Endocrinol (Lausanne) 11:615993. Crossref, Medline, Google Scholar2. Bahn RS 2010 Graves' ophthalmopathy. N Engl J Med 362:726–738. Crossref, Medline, Google Scholar3. Ahn HY, Lee J, Lee JK 2022 Predictive model for Graves' ophthalmopathy in patients with new-onset Graves' disease. Thyroid. Epub 2022 Nov 9. Link, Google Scholar4. Lee MH, Chin YH, Ng CH, Nistla KRY, Ow ZGW, Sundar G, Yang SP, Khoo CM 2021 Risk factors of thyroid eye disease. Endocr Pract 27:245–253. Crossref, Medline, Google Scholar5. Träisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, et al. 2009 Thyroid-associated ophthalmopathy after treatment for Graves' hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94:3700–3707. Crossref, Medline, Google Scholar6. Wiersinga W, Žarković M, Bartalena L, Donati S, Perros P, Okosieme O, et al. 2018 Predictive score for the development or progression of Graves' orbitopathy in patients with newly diagnosed Graves' hyperthyroidism. Eur J Endocrinol 178:635–643. Crossref, Medline, Google Scholar7. Sabini E, Mazzi B, Profilo MA, Mautone T, Casini G, Rocchi R, et al. 2018 High serum cholesterol is a novel risk factor for Graves' orbitopathy: Results of a cross-sectional study. Thyroid 28:386–394. Link, Google Scholar8. Nilsson A, Tsoumani K, Planck T 2021 Statins decrease the risk of orbitopathy in newly diagnosed patients with Graves disease. J Clin Endocrinol Metab 106:1325–1332. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Volume 35Issue 1Jan 2023 Information© Copyright 2023, Mary Ann Liebert, Inc.To cite this article:Kharisa N. Rachmasari and Omar El Kawkgi.Can We Predict Thyroid Eye Disease Occurrence and Progression in Newly Diagnosed Graves’ Disease?.Clinical Thyroidology®.Jan 2023.9-11.http://doi.org/10.1089/ct.2023;35.9-11Published in Volume: 35 Issue 1: January 17, 2023PDF download