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Erschienen in: Journal of Endocrinological Investigation 11/2016

01.11.2016 | Review

Relation between therapy options for Graves’ disease and the course of Graves’ ophthalmopathy: a systematic review and meta-analysis

verfasst von: H. X. Li, N. Xiang, W. K. Hu, X. L. Jiao

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 11/2016

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Abstract

Background

The relation between therapy options for Graves’ disease (GD) and the course of Graves’ ophthalmopathy (GO) are still controversial. Our aim was to compare the occurrence of development or worsening of GO in patients who were treated with antithyroid drugs (ATDs) or radioactive iodine (RAI) or thyroidectomy (TX).

Methods

We conducted a comprehensive search of the Embase and PubMed database. Odds ratio (OR) was used as a measure of the effect of therapy options for GD on the risk of development or worsening of GO. The analysis was further stratified by factors that could affect the treatment effects.

Results

Nine trials involving 1773 patients were included. RAI therapy showed a significant effect on the risk of development or worsening GO compared with ATD (OR 2.25; 95 % CI 1.61–3.14; P < 0.00001). Glucocorticoid prophylaxis was effective in preventing GO development or worsening (0.40; 0.23–0.68; P = 0.002); especially for patients with preexisting GO (0.41; 0.23–0.73; P = 0.002). At 3 months, showed GO to be improved in 17 TX and 21 total thyroid ablation (TTA) patients, with no significant difference between the two groups; between 6 and 12 months, TTA did show significant beneficial effect on the improvement of GO (6.02; 2.80–12.96; P < 0.00001); GO was found to be inactive in a significantly higher percentage of patients in the TTA (2.17; 1.04–4.52; P = 0.04).

Conclusion

Radioiodine therapy is a significant risk factor for development or worsening of GO in GD. But GO progression can be prevented by prophylactic glucocorticoids in patients with preexisting GO. Compared with TX alone, TTA induces an earlier and steadier GO improvement in patients with mild to moderate–severe and active GO. Whether this is sufficient to offer TTA to patients needs further investigation.
Literatur
1.
Zurück zum Zitat Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN, American Thyroid Association, American Association of Clinical Endocrinologists (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17(3):456–520PubMedCrossRef Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN, American Thyroid Association, American Association of Clinical Endocrinologists (2011) Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 17(3):456–520PubMedCrossRef
4.
Zurück zum Zitat Kung AW, Yau CC, Cheng A (1994) The incidence of ophthalmopathy after radioiodine therapy for Graves’ disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab 79(2):542–546. doi:10.1210/jcem.79.2.7913934 PubMed Kung AW, Yau CC, Cheng A (1994) The incidence of ophthalmopathy after radioiodine therapy for Graves’ disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab 79(2):542–546. doi:10.​1210/​jcem.​79.​2.​7913934 PubMed
5.
Zurück zum Zitat Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, Hallengren B, Hedner P, Lantz M, Nystrom E, Ponjavic V, Taube A, Torring O, Wallin G, Asman P, Lundell G, Thyroid Study Group of TT (2009) Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94(10):3700–3707. doi:10.1210/jc.2009-0747 PubMedCrossRef Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorff J, Hallengren B, Hedner P, Lantz M, Nystrom E, Ponjavic V, Taube A, Torring O, Wallin G, Asman P, Lundell G, Thyroid Study Group of TT (2009) Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94(10):3700–3707. doi:10.​1210/​jc.​2009-0747 PubMedCrossRef
6.
Zurück zum Zitat Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell’Unto E, Bruno-Bossio G, Nardi M, Bartolomei MP, Lepri A, Rossi G, Martino E, Pinchera A (1998) Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 338(2):73–78. doi:10.1056/NEJM199801083380201 PubMedCrossRef Bartalena L, Marcocci C, Bogazzi F, Manetti L, Tanda ML, Dell’Unto E, Bruno-Bossio G, Nardi M, Bartolomei MP, Lepri A, Rossi G, Martino E, Pinchera A (1998) Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 338(2):73–78. doi:10.​1056/​NEJM199801083380​201 PubMedCrossRef
7.
Zurück zum Zitat Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, Taube A (1992) Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med 326(26):1733–1738. doi:10.1056/NEJM199206253262603 PubMedCrossRef Tallstedt L, Lundell G, Torring O, Wallin G, Ljunggren JG, Blomgren H, Taube A (1992) Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med 326(26):1733–1738. doi:10.​1056/​NEJM199206253262​603 PubMedCrossRef
9.
Zurück zum Zitat Chen DY, Schneider PF, Zhang XS, Luo XY, He ZM, Chen TH (2014) Changes in graves’ ophthalmopathy after radioiodine and anti-thyroid drug treatment of Graves’ disease from 2 prospective, randomized, open-label, blinded end point studies. Exp Clin Endocrinol Diabetes 122(1):1–6. doi:10.1055/s-0033-1358484 PubMed Chen DY, Schneider PF, Zhang XS, Luo XY, He ZM, Chen TH (2014) Changes in graves’ ophthalmopathy after radioiodine and anti-thyroid drug treatment of Graves’ disease from 2 prospective, randomized, open-label, blinded end point studies. Exp Clin Endocrinol Diabetes 122(1):1–6. doi:10.​1055/​s-0033-1358484 PubMed
10.
Zurück zum Zitat Bonnema SJ, Bartalena L, Toft AD, Hegedus L (2002) Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres. Eur J Endocrinol 147(1):1–11PubMedCrossRef Bonnema SJ, Bartalena L, Toft AD, Hegedus L (2002) Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres. Eur J Endocrinol 147(1):1–11PubMedCrossRef
12.
Zurück zum Zitat Bartalena L, Tanda ML, Piantanida E, Lai A, Pinchera A (2004) Relationship between management of hyperthyroidism and course of the ophthalmopathy. J Endocrinol Invest 27(3):288–294PubMedCrossRef Bartalena L, Tanda ML, Piantanida E, Lai A, Pinchera A (2004) Relationship between management of hyperthyroidism and course of the ophthalmopathy. J Endocrinol Invest 27(3):288–294PubMedCrossRef
13.
14.
Zurück zum Zitat Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135(11):982–989PubMedCrossRef Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135(11):982–989PubMedCrossRef
15.
Zurück zum Zitat Menconi F, Marino M, Pinchera A, Rocchi R, Mazzi B, Nardi M, Bartalena L, Marcocci C (2007) Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Graves’ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 92(5):1653–1658. doi:10.1210/jc.2006-1800 PubMedCrossRef Menconi F, Marino M, Pinchera A, Rocchi R, Mazzi B, Nardi M, Bartalena L, Marcocci C (2007) Effects of total thyroid ablation versus near-total thyroidectomy alone on mild to moderate Graves’ orbitopathy treated with intravenous glucocorticoids. J Clin Endocrinol Metab 92(5):1653–1658. doi:10.​1210/​jc.​2006-1800 PubMedCrossRef
16.
Zurück zum Zitat Moleti M, Violi MA, Montanini D, Trombetta C, Di Bella B, Sturniolo G, Presti S, Alibrandi A, Campenni A, Baldari S, Trimarchi F, Vermiglio F (2014) Radioiodine ablation of postsurgical thyroid remnants after treatment with recombinant human TSH (rhTSH) in patients with moderate-to-severe graves’ orbitopathy (GO): a prospective, randomized, single-blind clinical trial. J Clin Endocrinol Metab 99(5):1783–1789. doi:10.1210/jc.2013-3093 PubMedCrossRef Moleti M, Violi MA, Montanini D, Trombetta C, Di Bella B, Sturniolo G, Presti S, Alibrandi A, Campenni A, Baldari S, Trimarchi F, Vermiglio F (2014) Radioiodine ablation of postsurgical thyroid remnants after treatment with recombinant human TSH (rhTSH) in patients with moderate-to-severe graves’ orbitopathy (GO): a prospective, randomized, single-blind clinical trial. J Clin Endocrinol Metab 99(5):1783–1789. doi:10.​1210/​jc.​2013-3093 PubMedCrossRef
17.
Zurück zum Zitat Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A (1989) Use of corticosteroids to prevent progression of Graves’ ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 321(20):1349–1352. doi:10.1056/NEJM198911163212001 PubMedCrossRef Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A (1989) Use of corticosteroids to prevent progression of Graves’ ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med 321(20):1349–1352. doi:10.​1056/​NEJM198911163212​001 PubMedCrossRef
18.
Zurück zum Zitat Watanabe N, Noh JY, Kozaki A, Iwaku K, Sekiya K, Kosuga Y, Matsumoto M, Suzuki M, Yoshihara A, Ohye H, Kobayashi S, Kunii Y, Mukasa K, Sugino K, Inoue T, Ito K (2015) Radioiodine-associated exacerbation of Graves’ orbitopathy in the Japanese population: randomized prospective study. J Clin Endocrinol Metab 100(7):2700–2708. doi:10.1210/jc.2014-4542 PubMedCrossRef Watanabe N, Noh JY, Kozaki A, Iwaku K, Sekiya K, Kosuga Y, Matsumoto M, Suzuki M, Yoshihara A, Ohye H, Kobayashi S, Kunii Y, Mukasa K, Sugino K, Inoue T, Ito K (2015) Radioiodine-associated exacerbation of Graves’ orbitopathy in the Japanese population: randomized prospective study. J Clin Endocrinol Metab 100(7):2700–2708. doi:10.​1210/​jc.​2014-4542 PubMedCrossRef
20.
Zurück zum Zitat Tallstedt L, Lundell G, Blomgren H, Bring J (1994) Does early administration of thyroxine reduce the development of Graves’ ophthalmopathy after radioiodine treatment? Eur J Endocrinol 130(5):494–497PubMedCrossRef Tallstedt L, Lundell G, Blomgren H, Bring J (1994) Does early administration of thyroxine reduce the development of Graves’ ophthalmopathy after radioiodine treatment? Eur J Endocrinol 130(5):494–497PubMedCrossRef
22.
Zurück zum Zitat Eckstein AK, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, Heckmann C, Esser J, Morgenthaler NG (2006) Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 91(9):3464–3470. doi:10.1210/jc.2005-2813 PubMedCrossRef Eckstein AK, Plicht M, Lax H, Neuhauser M, Mann K, Lederbogen S, Heckmann C, Esser J, Morgenthaler NG (2006) Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab 91(9):3464–3470. doi:10.​1210/​jc.​2005-2813 PubMedCrossRef
23.
Zurück zum Zitat Bartalena L, Marcocci C, Tanda ML, Manetti L, Dell’Unto E, Bartolomei MP, Nardi M, Martino E, Pinchera A (1998) Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 129(8):632–635PubMedCrossRef Bartalena L, Marcocci C, Tanda ML, Manetti L, Dell’Unto E, Bartolomei MP, Nardi M, Martino E, Pinchera A (1998) Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 129(8):632–635PubMedCrossRef
24.
Zurück zum Zitat Perros P, Kendall-Taylor P, Neoh C, Frewin S, Dickinson J (2005) A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves’ ophthalmopathy. J Clin Endocrinol Metab 90(9):5321–5323. doi:10.1210/jc.2005-0507 PubMedCrossRef Perros P, Kendall-Taylor P, Neoh C, Frewin S, Dickinson J (2005) A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves’ ophthalmopathy. J Clin Endocrinol Metab 90(9):5321–5323. doi:10.​1210/​jc.​2005-0507 PubMedCrossRef
27.
Zurück zum Zitat Marino M, Chiovato L, Lisi S, Altea MA, Marcocci C, Pinchera A (2004) Role of thyroglobulin in the pathogenesis of Graves’ ophthalmopathy: the hypothesis of Kriss revisited. J Endocrinol Invest 27(3):230–236. doi:10.1007/BF03345271 PubMedCrossRef Marino M, Chiovato L, Lisi S, Altea MA, Marcocci C, Pinchera A (2004) Role of thyroglobulin in the pathogenesis of Graves’ ophthalmopathy: the hypothesis of Kriss revisited. J Endocrinol Invest 27(3):230–236. doi:10.​1007/​BF03345271 PubMedCrossRef
29.
30.
Zurück zum Zitat Shiber S, Stiebel-Kalish H, Shimon I, Grossman A, Robenshtok E (2014) Glucocorticoid regimens for prevention of Graves’ ophthalmopathy progression following radioiodine treatment: systematic review and meta-analysis. Thyroid 24(10):1515–1523. doi:10.1089/thy.2014.0218 PubMedCrossRef Shiber S, Stiebel-Kalish H, Shimon I, Grossman A, Robenshtok E (2014) Glucocorticoid regimens for prevention of Graves’ ophthalmopathy progression following radioiodine treatment: systematic review and meta-analysis. Thyroid 24(10):1515–1523. doi:10.​1089/​thy.​2014.​0218 PubMedCrossRef
31.
Zurück zum Zitat Vannucchi G, Campi I, Covelli D, Dazzi D, Curro N, Simonetta S, Ratiglia R, Beck-Peccoz P, Salvi M (2009) Graves’ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab 94(9):3381–3386. doi:10.1210/jc.2009-0506 PubMedCrossRef Vannucchi G, Campi I, Covelli D, Dazzi D, Curro N, Simonetta S, Ratiglia R, Beck-Peccoz P, Salvi M (2009) Graves’ orbitopathy activation after radioactive iodine therapy with and without steroid prophylaxis. J Clin Endocrinol Metab 94(9):3381–3386. doi:10.​1210/​jc.​2009-0506 PubMedCrossRef
32.
Zurück zum Zitat Lai A, Sassi L, Compri E, Marino F, Sivelli P, Piantanida E, Tanda ML, Bartalena L (2010) Lower dose prednisone prevents radioiodine-associated exacerbation of initially mild or absent graves’ orbitopathy: a retrospective cohort study. J Clin Endocrinol Metab 95(3):1333–1337. doi:10.1210/jc.2009-2130 PubMedCrossRef Lai A, Sassi L, Compri E, Marino F, Sivelli P, Piantanida E, Tanda ML, Bartalena L (2010) Lower dose prednisone prevents radioiodine-associated exacerbation of initially mild or absent graves’ orbitopathy: a retrospective cohort study. J Clin Endocrinol Metab 95(3):1333–1337. doi:10.​1210/​jc.​2009-2130 PubMedCrossRef
33.
Zurück zum Zitat Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM, European Group on Graves O (2008) Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158(3):273–285. doi:10.1530/EJE-07-0666 PubMedCrossRef Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM, European Group on Graves O (2008) Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158(3):273–285. doi:10.​1530/​EJE-07-0666 PubMedCrossRef
34.
Zurück zum Zitat Volpe R (2001) The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte–immunocyte signalling: a review. Curr Pharm Des 7(6):451–460PubMedCrossRef Volpe R (2001) The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte–immunocyte signalling: a review. Curr Pharm Des 7(6):451–460PubMedCrossRef
35.
Zurück zum Zitat Weetman AP, McGregor AM, Hall R (1984) Evidence for an effect of antithyroid drugs on the natural history of Graves’ disease. Clin Endocrinol 21(2):163–172CrossRef Weetman AP, McGregor AM, Hall R (1984) Evidence for an effect of antithyroid drugs on the natural history of Graves’ disease. Clin Endocrinol 21(2):163–172CrossRef
Metadaten
Titel
Relation between therapy options for Graves’ disease and the course of Graves’ ophthalmopathy: a systematic review and meta-analysis
verfasst von
H. X. Li
N. Xiang
W. K. Hu
X. L. Jiao
Publikationsdatum
01.11.2016
Verlag
Springer International Publishing
Erschienen in
Journal of Endocrinological Investigation / Ausgabe 11/2016
Elektronische ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-016-0484-y

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