THYROID Volume 24, Number 10, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2014.0349
Steroid Prophylaxis After Radioiodine Treatment for Graves’ Hyperthyroidism: Selective or Universal? Luigi Bartalena
G
raves’ ophthalmopathy (GO) is the most frequent and important extrathyroidal manifestation of Graves’ disease (1). The majority of newly diagnosed Graves’ patients have no GO (2), and the orbital disease rarely develops de novo or progresses during antithyroid drug treatment for hyperthyroidism (3). It is widely accepted that, in addition to ill-defined genetic factors, environmental (exogenous) factors play a relevant role in the development or progression of GO (1). These include cigarette smoking, poorly controlled thyroid dysfunction (both hyperthyroidism and hypothyroidism), oxidative stress, high thyrotropin-receptor antibody levels, and radioiodine (RAI) treatment (1). Accordingly, abstaining from smoking, prompt restoration and maintenance of euthyroidism, and a course of selenium supplementation (when mild GO is present) are considered as important actions for preventing GO progression (1). RAI is an effective and widely used form of treatment for Graves’ hyperthyroidism, but its use has been associated with a low, although not negligible risk of GO progression, especially in patients with preexisting GO, in smokers (4), and if post-RAI hypothyroidism is not promptly corrected (5). This has raised concerns on its use in patients with established GO. Patients with absent or inactive GO are at very low risk of GO development after RAI; on the other hand, patients with moderate to severe and active GO should receive prompt treatment for orbital disease (usually systemic immunosuppression by high-dose glucocorticoids) and are generally maintained euthyroid with antithyroid drug treatment while the GO is being treated (5). Whether RAI treatment can be safely used in patients with mild and active GO or inactive GO (but in the presence of one or more of the risk factors mentioned above) is a matter of debate (6). In the present issue of Thyroid, Shiber et al. (7) carried out a systematic review and meta-analysis of available studies addressing the efficacy of steroid prophylaxis in preventing RAI-associated development or exacerbation of GO. Eight trials evaluating 850 patients fulfilled inclusion criteria. This carefully performed analysis of the scarce available data in the literature led to the conclusion that a short course of glucocorticoids given for a few weeks after RAI administration is an effective preventive measure in patients with mild to moderate GO,
especially if risk factors for post-RAI progression are present (7). Glucocorticoids are usually given orally and at low doses. Shiber et al. (7) propose that the standard starting dose of prednisone (0.4–0.5 mg/kg body weight, tapered down and withdrawn after 3 months) be given to patients with mild to moderate GO, while a lower dose (0.2–0.3 mg/kg body weight, tapered down and withdrawn after 6 weeks), recently reported in a retrospective study to be equally effective (8), might be used in patients with even milder forms or in those who have no GO prior to RAI treatment, but present risk factors for GO development (especially smoking). As proposed also by other authors (9), Shiber et al. (7) suggest that patients without preexisting GO (or with inactive GO) and without risk factors could safely receive RAI treatment without steroid coverage. In principle, this statement is correct, because randomized clinical trials showing that steroid prophylaxis is beneficial also in this category of patients are lacking. Admittedly, the risk that GO develops or progresses in these patients is extremely low. On the other hand, we should not forget that moderate to severe GO is an invalidating and disfiguring disease, and represents a major therapeutic problem, because currently available medical treatments are very often only partially effective (1); for this reason, rehabilitative surgery, frequently requiring multiple procedures, is eventually necessary in many patients. Therefore, I believe that the issue of possible steroid prophylaxis should be presented and discussed in a balanced manner (pros and cons) also with these patients (no GO and no risk factors) when planning RAI treatment. In summary, the excellent systematic review and metaanalysis by Shiber et al. (7) confirms the usefulness and effectiveness of steroid prophylaxis after RAI treatment in patients with mild and active GO and/or with risk factors for RAI-associated development or progression of the orbitopathy. Based on evidence, patients with no GO and no risk factors are highly unlikely to have this undue effect of RAI if they are treated without steroid prophylaxis. Author Disclosure Statement
No competing financial interests exist.
Department of Clinical & Experimental Medicine, University of Insubria, Varese, Italy.
1441
1442 References
1. Bartalena L, Fatourechi V 2014 Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Invest 37:691–700. 2. Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L 2013 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 98:1443–1449. 3. Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L 2013 Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 36:444–449. 4. Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorf J, Hallengren B, Hedner P, lantz M, Nystrom E, Pnjavic V, Taube A, Torring O, Wallin G, Asman P, Lundell G 2009 Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94:3700–3707. 5. 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 130:494–497. 6. Bartalena L 2011 The dilemma of how to manage Graves’ hyperthyroidism in patients with associated orbitopathy. J Clin Endocrinol Metab 96:592–599. 7. Shiber S, Stiebel-Kalish H, Shimon I, Grossman A, Robensthok E 2014 Glucocorticoids regimens for prevention of
EDITORIAL
Graves’ ophthalmopathy progression following radioiodine treatment—Systematic review and meta-analysis. Thyroid 24:1515–1523. 8. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi C, Azzolini C, Boboridis KG, Mourits MP, Soeters MR, Baldeschi L, Nardi M, Curro` N, Boschi A, Bernard M, von Arx G, European Group on Graves’ Orbitopathy 2012 Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 97:4454–4463. 9. 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 90:5321–5323.
Address correspondence to: Luigi Bartalena, MD Department of Clinical & Experimental Medicine University of Insubria Endocrine Unit Ospedale di Circolo Viale Borri, 57 21100 Varese Italy E-mail: [email protected]
Steroid Prophylaxis After Radioiodine Treatment for Graves’ Hyperthyroidism: Selective or Universal? Luigi Bartalena
G
raves’ ophthalmopathy (GO) is the most frequent and important extrathyroidal manifestation of Graves’ disease (1). The majority of newly diagnosed Graves’ patients have no GO (2), and the orbital disease rarely develops de novo or progresses during antithyroid drug treatment for hyperthyroidism (3). It is widely accepted that, in addition to ill-defined genetic factors, environmental (exogenous) factors play a relevant role in the development or progression of GO (1). These include cigarette smoking, poorly controlled thyroid dysfunction (both hyperthyroidism and hypothyroidism), oxidative stress, high thyrotropin-receptor antibody levels, and radioiodine (RAI) treatment (1). Accordingly, abstaining from smoking, prompt restoration and maintenance of euthyroidism, and a course of selenium supplementation (when mild GO is present) are considered as important actions for preventing GO progression (1). RAI is an effective and widely used form of treatment for Graves’ hyperthyroidism, but its use has been associated with a low, although not negligible risk of GO progression, especially in patients with preexisting GO, in smokers (4), and if post-RAI hypothyroidism is not promptly corrected (5). This has raised concerns on its use in patients with established GO. Patients with absent or inactive GO are at very low risk of GO development after RAI; on the other hand, patients with moderate to severe and active GO should receive prompt treatment for orbital disease (usually systemic immunosuppression by high-dose glucocorticoids) and are generally maintained euthyroid with antithyroid drug treatment while the GO is being treated (5). Whether RAI treatment can be safely used in patients with mild and active GO or inactive GO (but in the presence of one or more of the risk factors mentioned above) is a matter of debate (6). In the present issue of Thyroid, Shiber et al. (7) carried out a systematic review and meta-analysis of available studies addressing the efficacy of steroid prophylaxis in preventing RAI-associated development or exacerbation of GO. Eight trials evaluating 850 patients fulfilled inclusion criteria. This carefully performed analysis of the scarce available data in the literature led to the conclusion that a short course of glucocorticoids given for a few weeks after RAI administration is an effective preventive measure in patients with mild to moderate GO,
especially if risk factors for post-RAI progression are present (7). Glucocorticoids are usually given orally and at low doses. Shiber et al. (7) propose that the standard starting dose of prednisone (0.4–0.5 mg/kg body weight, tapered down and withdrawn after 3 months) be given to patients with mild to moderate GO, while a lower dose (0.2–0.3 mg/kg body weight, tapered down and withdrawn after 6 weeks), recently reported in a retrospective study to be equally effective (8), might be used in patients with even milder forms or in those who have no GO prior to RAI treatment, but present risk factors for GO development (especially smoking). As proposed also by other authors (9), Shiber et al. (7) suggest that patients without preexisting GO (or with inactive GO) and without risk factors could safely receive RAI treatment without steroid coverage. In principle, this statement is correct, because randomized clinical trials showing that steroid prophylaxis is beneficial also in this category of patients are lacking. Admittedly, the risk that GO develops or progresses in these patients is extremely low. On the other hand, we should not forget that moderate to severe GO is an invalidating and disfiguring disease, and represents a major therapeutic problem, because currently available medical treatments are very often only partially effective (1); for this reason, rehabilitative surgery, frequently requiring multiple procedures, is eventually necessary in many patients. Therefore, I believe that the issue of possible steroid prophylaxis should be presented and discussed in a balanced manner (pros and cons) also with these patients (no GO and no risk factors) when planning RAI treatment. In summary, the excellent systematic review and metaanalysis by Shiber et al. (7) confirms the usefulness and effectiveness of steroid prophylaxis after RAI treatment in patients with mild and active GO and/or with risk factors for RAI-associated development or progression of the orbitopathy. Based on evidence, patients with no GO and no risk factors are highly unlikely to have this undue effect of RAI if they are treated without steroid prophylaxis. Author Disclosure Statement
No competing financial interests exist.
Department of Clinical & Experimental Medicine, University of Insubria, Varese, Italy.
1441
1442 References
1. Bartalena L, Fatourechi V 2014 Extrathyroidal manifestations of Graves’ disease: a 2014 update. J Endocrinol Invest 37:691–700. 2. Tanda ML, Piantanida E, Liparulo L, Veronesi G, Lai A, Sassi L, Pariani N, Gallo D, Azzolini C, Ferrario M, Bartalena L 2013 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 98:1443–1449. 3. Piantanida E, Tanda ML, Lai A, Sassi L, Bartalena L 2013 Prevalence and natural history of Graves’ orbitopathy in the XXI century. J Endocrinol Invest 36:444–449. 4. Traisk F, Tallstedt L, Abraham-Nordling M, Andersson T, Berg G, Calissendorf J, Hallengren B, Hedner P, lantz M, Nystrom E, Pnjavic V, Taube A, Torring O, Wallin G, Asman P, Lundell G 2009 Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 94:3700–3707. 5. 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 130:494–497. 6. Bartalena L 2011 The dilemma of how to manage Graves’ hyperthyroidism in patients with associated orbitopathy. J Clin Endocrinol Metab 96:592–599. 7. Shiber S, Stiebel-Kalish H, Shimon I, Grossman A, Robensthok E 2014 Glucocorticoids regimens for prevention of
EDITORIAL
Graves’ ophthalmopathy progression following radioiodine treatment—Systematic review and meta-analysis. Thyroid 24:1515–1523. 8. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi C, Azzolini C, Boboridis KG, Mourits MP, Soeters MR, Baldeschi L, Nardi M, Curro` N, Boschi A, Bernard M, von Arx G, European Group on Graves’ Orbitopathy 2012 Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves’ orbitopathy. J Clin Endocrinol Metab 97:4454–4463. 9. 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 90:5321–5323.
Address correspondence to: Luigi Bartalena, MD Department of Clinical & Experimental Medicine University of Insubria Endocrine Unit Ospedale di Circolo Viale Borri, 57 21100 Varese Italy E-mail: [email protected]
