and selenium are micronutrients essential to thyroid hormone production and action. Chronic high iodine intake has been associated with an increased frequency of chronic autoimmune thyroiditis, thyroperoxidase antibodies, and autoimmune hypothyroidism. The incidence of moderate-to-severe GO was not changed after iodine fortification of salt in Denmark [3].
Recent epidemiological studies from China provide strong circumstantial evidence that low selenium intake is associated with Hashimoto’s thyroiditis and hypothyroidism, but not with Graves’ disease and hyperthyroidism [35].
As both deficiency and excess intake of iodine and selenium can be deleterious for thyroid function, dietary advice should aim at maintenance of normal intake.
One Korean series and isolated case reports describe mild to moderate-to-severe GO in patients without a history of Graves’ disease, occurring after thyroidectomy or 131I therapy for nodular goitre or thyroid cancer [36]. Some of these patients had total thyroid ablation with no detectable thyroid tissue and no evidence of prior TSH-R autoantibodies [37].
The authors hypothesized that radioiodine treatment or thyroid damage during surgery induced thyroid autoimmunity. This pathogenic explanation is less evident in GO cases diagnosed up to 9 years after thyroid intervention in whom the role of other triggers acting on orbital fibroblasts may prevail.
All but 1 of the above cases were overtreated by thyroid hormones at GO diagnosis, and it is well recognized that euthyroidism is required for GO prevention/improvement. Whether prolonged exogenous hyperthyroidism could promote orbital inflammation by altering local thyroid hormone metabolism needs to be investigated. No case of GO has been described in congenitally athyreotic patients.
1 Bartley GB, Fatourechi V, Kardrmas EF, Jacbsen SJ, Ilstrup DM, Garrity JA, Gorman CA: The incidence of Graves’ ophthalmopathy in an incidence cohort. Am J Ophthalmol 1995;121:284–290.
2 Abraham-Nordling M, Bystrom K, Torring O, Lantz M, Berg G, Calissendorf J, et al: Incidence of hyperthyroidism in Sweden. Eur J Endocrinol 2011;165:899–905.
3 Laurberg P, Berman DC, Bulow-Pedersen I, Andersen S, Carle 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;97:2325–2332.
4 Perros P, Hegedüs L, Bartalena L, et al: Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement. Orphanet J Rare Dis 2017;12:72.
5 Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrio M, Bartalena L. Prevalence of natural history of Graves’ orbitopathy in a large series of patients with newly diagnosed Graves’ hyperthyroidism seen in a single center. J Clin Endocrinol Metab 2013;98:1443–1449.
6 Perros P, Kendall-Taylor P: Natural history of thyroid eye disease. Thyroid 1998;8:423–425.
7 Weetman AP, Wiersinga WM: Current management of thyroid-associated opthalmopathy in Europe. Results of an international survey. Clin Endocrinol 1998;49:21–28.
8 Perros P, Zarkovic M, Azzolini C, Ayvaz G, Baldeschi L, Bartalena L, Bernard M, et al: PREGO (Presentation of Graves’ Orbitopathy) study: changes in referral patterns to European Group on Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012. Br J Ophthalmol 2015;99:1531–1535.
9 Prummel MF, Wiersinga WM: Smoking and risk of Graves’ disease. JAMA 1993;269:479–482.
10 Prummel MF, Bakker A, Wiersinga WM, Baldeschi L, Mourits MP, Kendall-Taylor P, Perros P, Neoh C, Dickinson AJ, Lazarus JH, Lane CM, Heufelder AE, Kahaly GJ, Pitz S, Orgiazzi J, Hullo A, Pinchera A, Marcocci C, Sartini MS, Rocchi R, Nardi M, Krassas GE, Halkias A: Multi-center study on the characteristics and treatment strategies of patients with Graves’ orbitopathy: the first European Group on Graves’ Orbitopathy experience. Eur J Endocrinol 2003;148:491–495.
11 Teller M, Cooper J, Edmonds C: Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin. Clin Endocrinol 1992;36:291–294.
12 Lim SL, Lim AK, Mumtaz M, Hussein E, Wan Bebakar WM, Khir AS: Prevalence, risk factors, and clinical features of thyroid-associated ophthalmopathy in multiethnic Malaysian patients with Graves’ disease. Thyroid 2008;18:1297–1301.
13 Tsai CC, Kau HC, Kao SC, Hsu WM: Exophthalmos of patients with Graves’ disease in Chinese of Taiwan. Eye 2006;20:569–577.
14 Villanueva R, Inzerillo AM, Tomer Y, Barbesino G, Meltzer M, Concepcion ES, Greenberg DA, Maclaren N, Sun ZS, Zhang DM, Tucci S, Davies TF: Limited genetic susceptibility to severe Graves’ ophthalmopathy: no role for CTLA-4 but evidence for an environmental etiology. Thyroid 2000;10:791–798.
15 Bednarczuk T, Gopinath B, Ploski R, Wall JR: Susceptibility genes in Graves’ ophthalmopathy: searching for a needle in a haystack? Clin Endocrinol 2007;67:3–19.
16 Khalilzadeh O, Anvari M, Esteghamati A, Mahmoudi M, Tahvildari M, Rashidi A, Khosravi F, Amirzargar A: Graves’ ophthalmopathy and gene polymorphisms in interleukin-1alpha, interleukin-1beta, interleukin-1 receptor and interleukin-1 receptor antagonist. Clin Exp Ophthalmol 2009;37:614–619.
17 Eckstein AK, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, Heckmann C, Esser J, Morgenthaler NG: Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 2006;91:3464–3470.
18 Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, Taube A: Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992;326:1733–1738.