This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marcocci, C. Articles by Pinchera, A. Search for Related Content PubMed PubMed Citation Articles by Marcocci, C. Articles by Pinchera, A.

Comparison of the Effectiveness and Tolerability of Intravenous or Oral Glucocorticoids Associated with Orbital Radiotherapy in the Management of Severe Graves’ Ophthalmopathy: Results of a Prospective, Single-Blind, Randomized Study

Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro (C.M., M.L.T., L.M., E.D.U., R.R., G.B., B.M., A.P.), Dipartimento di Neuroscienze (M.P.B., P.L., M.N.) e Dipartimento di Oncologia (F.C.), University of Pisa, 56124 Pisa, Italy; and Cattedra di Endocrinologia, University of Insubria (L.B.), Varese 21100, Italy

Address all correspondence and requests for reprints to: Claudio Marcocci, M.D., Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Via Paradisa 2, 56124 Pisa, Italy. E-mail: c.marcocci{at}endoc.med.unipi.it

Abstract

Eighty-two consecutive patients with moderate-to-severe and active Graves’ ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves’ ophthalmopathy. Follow-up lasted for 12 months.

A significant reduction in proptosis (from 23.2 ± 3.0 to 21.6 ± 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 ± 1.8 to 21.7 ± 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 ± 2.5 to 11.8 ± 2.2 mm, and from 13.6 ± 2.0 to 11.5 ± 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 ± 1.2 to 1.7 ± 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 ± 1.1 to 2.2 ± 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery.

In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves’ ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.

This article has been cited by other articles:

				L. Bartalena, L. Baldeschi, A. Dickinson, A. Eckstein, P. Kendall-Taylor, C. Marcocci, M. Mourits, P. Perros, K. Boboridis, A. Boschi, et al. Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO Eur. J. Endocrinol., March 1, 2008; 158(3): 273 - 285. [Full Text] [PDF]

				R. J van Geest, I. V Sasim, H. P F Koppeschaar, R. Kalmann, S. N Stravers, W. R Bijlsma, and M. P Mourits Methylprednisolone pulse therapy for patients with moderately severe Graves' orbitopathy: a prospective, randomized, placebo-controlled study Eur. J. Endocrinol., February 1, 2008; 158(2): 229 - 237. [Abstract] [Full Text] [PDF]

				F. Menconi, M. Marino, A. Pinchera, R. Rocchi, B. Mazzi, M. Nardi, L. Bartalena, and C. Marcocci Effects of Total Thyroid Ablation Versus Near-Total Thyroidectomy Alone on Mild to Moderate Graves' Orbitopathy Treated with Intravenous Glucocorticoids J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1653 - 1658. [Abstract] [Full Text] [PDF]

				M. Salvi, G. Vannucchi, I. Campi, N. Curro, D. Dazzi, S. Simonetta, P. Bonara, S. Rossi, C. Sina, C. Guastella, et al. Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study Eur. J. Endocrinol., January 1, 2007; 156(1): 33 - 40. [Abstract] [Full Text] [PDF]

				The European Group of Graves' Orbitopathy, P Perros, L Baldeschi, K Boboridis, A J Dickinson, A Hullo, G J Kahaly, P Kendall-Taylor, G E Krassas, C M Lane, et al. A questionnaire survey on the management of Graves' orbitopathy in Europe. Eur. J. Endocrinol., August 1, 2006; 155(2): 207 - 211. [Abstract] [Full Text] [PDF]

				J. A. P. DA SILVA, J. W. G. JACOBS, and J. W. J. BIJLSMA Revisiting the Toxicity of Low-Dose Glucocorticoids: Risks and Fears Ann. N.Y. Acad. Sci., June 1, 2006; 1069(1): 275 - 288. [Abstract] [Full Text] [PDF]

				J A P Da Silva, J W G Jacobs, J R Kirwan, M Boers, K G Saag, L B S Ines, E J P de Koning, F Buttgereit, M Cutolo, H Capell, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data Ann Rheum Dis, March 1, 2006; 65(3): 285 - 293. [Abstract] [Full Text] [PDF]

				L. Bartalena Glucocorticoids for Graves' Ophthalmopathy: How and When J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5497 - 5499. [Full Text] [PDF]

				G. J. Kahaly, S. Pitz, G. Hommel, and M. Dittmar Randomized, Single Blind Trial of Intravenous versus Oral Steroid Monotherapy in Graves' Orbitopathy J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5234 - 5240. [Abstract] [Full Text] [PDF]

				S. Savastano, R. Pivonello, W. Acampa, M. Salvatore, G. Lombardi, A. Colao, and G. Fenzi Recombinant Thyrotropin-Induced Orbital Uptake of [111In-Diethylenetriamine-Pentacetic Acid-D-Phe1]Octreotide in a Patient with Inactive Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2440 - 2444. [Abstract] [Full Text] [PDF]

				C. Marcocci, L. Bartalena, R. Rocchi, M. Marino, F. Menconi, E. Morabito, B. Mazzi, S. Mazzeo, M. S. Sartini, M. Nardi, et al. Long-Term Safety of Orbital Radiotherapy for Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3561 - 3566. [Abstract] [Full Text] [PDF]