Risk Factors Associated with the Activity and Severity of Graves’ Ophthalmopathy among Patients at the University of the Philippines Manila-Philippine General Hospital

Annabelle Marie Lat, Maria Cristina Jauculan, Charisse Ann Sanchez, Cecilia Jimeno, Cherrie Mae Sison-Peña, Mary Rose Pe-Yan, Paulo Ma. Pagkatipunan, Armida Suller, Marianne Cena


Background. Asians with Graves’ ophthalmopathy (GO) may have earlier compressive features due to narrower orbital apex and increased orbital volume.

Objective. To determine the risk factors associated with activity and severity of GO among adults.

Methodology. This was a cross-sectional analytical study of 163 adults with Graves’ disease (GD) from the outpatient clinics of the Philippine General Hospital. Demographics, clinical data, thyrotropin receptor antibody (TRAb) and urine iodine (UIE) levels were obtained. All participants were evaluated for activity and severity of GO by a single ophthalmologist.

Results. The population was predominantly composed of females (81%) and nonsmokers (69%), with a mean age of 35 + 11 years and median GD duration of 2 years. Median TRAb was 8.9 U/L while UIE was 171 mcg/L. Eight percent exhibited active GO, with 85% having mild disease. Multivariate analysis showed male sex to be associated with severe disease (OR 3.71, p=0.041), while elevated TRAb was associated with both active (OR 1.03, p=0.002) and severe GO (OR 1.02, p=0.007).

Conclusion. Lower rates of active and severe GO were seen compared to previous reports. In this population of predominantly nonsmokers, elevated TRAb emerged as a risk factor for active and severe GO.


Graves’ ophthalmopathy, Graves’ disease, thyrotropin receptor antibody

Full Text:

Abstract HTML


Abboud M, Arabi A, Salti I, Geara F. Outcome of thyroid associated ophthalmopathy treated by radiation therapy. Radiat Oncol. 2011;6:46-51. PMCID: PMC3108307. https://doi.org/10.1186/1748-717X-6-46.

Palisoc E, Morabe E, Pagkatipunan PM. Prevalence of Graves' ophthalmopathy among patients with thyroid disease. Philipp J Ophthalmol. 2010; 35(1):32-5.

Maheshwari R, Weis E. Thyroid associated orbitopathy. Indian J Ophthalmol. 2010; 60: 87-92. https://doi.org/10.4103/0301-4738.94048.

Kalmann R, Mourits MP. Diabetes Mellitus: A risk factor in patients with Graves’ orbitopathy. Br J Ophthalmol. 1999;83(4):463-5. PMCID: PMC1723016.

Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L. Prevalence and natural history of Graves’ orbitopathy in the XXI century. J. Endocrinol. Invest. 2013;36(6): 444-9. PMID: 23587873. https://doi.org/10.3275/8937.

Lim SL, Lim AKE, Mumtaz M, Hussein E, Bebakar WMW, Khir AS. Prevalence, risk factors, and clinical features of thyroid-associated ophthalmopathy in multiethnic Malaysian patients with Graves’ disease. Thyroid. 2008;18(12): 1297-301. PMID: 19012471. https://doi.org/10.1089/thy.2008.0044.

Besharati MR, Rastegar A. Clinical study of ophthalmopathy in patients with Graves’ disease. Asian J of Ophthalmol. 2005;7(3): 108-12.

Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol (Oxf). 1992;36(3):291-4. PMID: 1563082.

Bartalena L, Pinchera A, Marcocci C. Management of Graves’ ophthalmopathy: Reality and perspectives. Endocr Rev. 2000;21(2):168-99. PMID: 10782363. https://doi.org/10.1210/edrv.21.2.0393.

Stan MN, Bahn RS. Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid. 2010; 20(7):777-83. PMID: 20578901. PMCID: PMC3357079. https://doi.org/10.1089/thy.2010.1634.

Laurberg P, Berman D, Pedersen I, Andersen S, Carlé A. Incidence and clinical presentation of moderate to severe Graves’ orbitopathy in a Danish population before and after iodine fortification of salt. J Clin Endocrinol Metab. 2012;97(7):2325-32. PMCID: PMC3387399.

Food and Nutrition Research Institute-Department of Science and Technology. 7th National nutrition survey: 2008. http://www.fnri.dost.gov.ph/index.php/19-nutrition-statistic/108-7th-national-nutrition-survey. Accessed November 7, 2015.

Prummel M, Strieder T, Wiersinga W. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150(5):605–18.PMID: 15132715. https://doi.org/ 10.1530/eje.0.1500605.

Campi I, Vannucchi G, Salvi M. Endocrine dilemma: Management of Graves’ orbitopathy. Eur J Endocrinol. 2016; 175: R117-133. https://doi.org/ 10.1530/EJE-15-1164.

Lee JH, Lee SY, Yoon JS. Risk factors associated with the severity of thyroid-associated orbitopathy in Korean patients. Korean J Ophthalmol. 2010;24(5): 267-73. PMCID: PMC2955268. https://doi.org/10.3341/kjo.2010.24.5.267.

Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, et.al. Prevalence and natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed Graves’ hyperthyroidism seen at a single center. J Clin Endocrinol Metab. 2013;98(4):1443-9. PMID: 23408569. https://doi/org/10.1210/jc.2012-3873.

Chan LL, Tan HE, Fook-Chong S, Teo TH, Lim LH, Seah LL. Graves’ ophthalmopathy: The bony orbit in optic neuropathy, its apical angular capacity, and impact on prediction of risk. AJNR Am J Neuroradiol. 2009;30(3):597-602. PMID: 19147718. https://doi.org/10.3174/ajnr.A1413.

Wiersinga WM. Graves’ orbitopathy: Management of difficult cases. Indian J Endocr Metab. 2012;16(Suppl 2):S150-2. PMCID: PMC3603013.

Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy guidelines for the management of Graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9-26. PMID: 27099835. PMCID: PMC4836120. https://doi.org/10.1159/000443828.

Zang S, Ponto KA, Kahaly GJ. Clinical review: Intravenous glucocorticoids for Graves’ orbitopathy: Efficacy and morbidity. J Clin Endocrinol Metab. 2011; 96(2):320-32. PMID: 21239515. https://doi.org/10.1210/jc.2010-1962.

Palmero MO, Lucarelli MJ. Evolving techniques in orbital decompression of thyroid orbitopathy. Philipp J Ophthalmol. 2007;32(1):28-31.

Ponto KA, Pitz S, Pfeiffer N, Hommel G, Webber MM, Kahaly GJ. Quality of life and occupational disability in endocrine orbitopathy. Dtsch Arztebl Int. 2009; 106(17):283-9. PMID: 19547630. PMCID: PMC2689575. https://doi.org/10.3238/arztebl.2009.0283.

Virola, R. “How rich is rich?” Family income and expenditures survey and consumer Price indexes of the National Statistics Office. 2010. http://www.nscb.gov.ph/headlines/StatsSpeak/2010/061510_rav_joe.asp. Accessed November 7, 2015.

Rundle FF, Wilson CW. Development and course of exophthalmos and ophthalmoplegia in Graves’ disease with special reference to the effect of thyroidectomy. Clin Sci. 1945;5(3-4):177-94. PMID: 21011937.

Savku E, Gündüz K. Diagnosis, follow-up and treatment results in thyroid ophthalmopathy. Turk J Ophthalmol. 2015;45(4):156-63. PMCID: PMC5082274. https://doi.org/ 10.4274/tjo.93609.

Khong JJ, Finch S, De Silva C, Rylander S, Craig JE, Selva D, et al. Risk factors for Graves’ orbitopathy; The Australian thyroid-associated orbitopathy research (ATOR) study. J Clin Endocrinol Metab. 2016;101(7):2711-20. PMID: 27055083. https://doi.org/10.1210/jc.2015-4294.

Mukasa K, Noh JY, Kouzaki A, et al. TSH receptor antibody titers measured with a third-generation assay did not reflect the activity of Graves’ ophthalmopathy in untreated Japanese Graves’ disease patients. Endocr J. 2016; 63(2):151-7. https://doi.org/10.1507/endocrj.EJ15-0137.

Lim NC, Sundar G, Amrith S, Lee KO. Thyroid eye disease: A Southeast Asian experience. Br J Ophthalmol. 2015;99(4):512-8. PMID: 25361748. https://doi.org/10.1136/bjophthalmol-2014-305649.

Pfeilschifter J, Ziegler R. Smoking and endocrine ophthalmopathy: Impact of smoking severity and current vs. lifetime cigarette consumption. Clin Endocrinol (Oxf). 1996; 45: 477–81. PMID: 8959089.

Gerding MN, van der Meer JWC, Broenink M, Bakker O, Wiersinga WM, Prummel MF. Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 2000; 52(3):267-71. PMID: 10718823.

Noh JY, Hamada N, Inoue Y, Abe Y, Ito K, Ito K. Thyroid-stimulating antibody is related to Graves’ ophthalmopathy, but thyrotropin-binding inhibitor immunoglobulin is related to hyperthyroidism in patients with Graves’ disease. Thyroid. 2000;10(9):809-13. PMID: 11041459. https://doi.org/10.1089/thy.2000.10.809.

Woo YJ, Jang SY, Lim THT, Yoon JS. Clinical association of thyroid stimulating hormone receptor antibody levels with disease severity in the chronic inactive stage of Graves’ orbitopathy. Korean J Ophthalmol. 2015; 29(4):213-9. PMCID: PMC4520863. https://doi.org/10.3341/kjo.2015.29.4.213.

Massart C, Sapin R, Gibassier J, Agin A, d’Herbomez M. Intermethod variability in TSH-receptor antibody measurement: Implication for the diagnosis of Graves disease and for the follow-up of Graves ophthalmopathy. Clin Chem. 2009; 55(1):183-6. PMID: 19028818. https://doi.org/10.1373/clinchem.2008.115162.

Kamath C, Adlan MA, Premawardhana LD. The role of thyrotrophin receptor antibody assays in Graves’ disease. J Thyroid Res. 2012;2012:525936. PMID: 22577596. PMCID: PMC3345237. https://doi.org/10.1155/2012/525936.

Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of disease. J Clin Endocrinol Metab. 2006;91(9):3464-70.PMID: 16835285. https://doi.org/10.1210/jc.2005-2813.

Iyer S, Bahn R. Immunopathogenesis of Graves’ ophthalmopathy: The role of the TSH receptor. Best Pract Res Clin Endocrinol Metab. 2012;26(3):281-9. PMCID: PMC3361679. NIHMSID: NIHM334372. https://doi.org/10.1016/j.beem.2011.10.003.

Smith TJ, Janssen JA. Building the case for insulin-like growth factor receptor-I involvement in thyroid-associated ophthalmopathy. Front Endocrinol (Lausanne). 2016;7:167. PMCID: PMC5206614. https://doi.org/ 10.3389/fendo.2016.00167.

Smith TJ. TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy. Nat Rev Endocrinol. 2015;11(3):171-81. PMID: 25560705. PMCID: PMC4687015. https://doi10.1038/nrendo.2014.226.