CASE REPORT Clinical Evaluation of the Long-Term Response to Intravenous Pulses of Methylprednisolone in Patients With Moderate to Severe Graves Ophthalmopathy Carla Amaral de Almeida, MD, Leonardo Vieira Neto, MD, Alexandru Buescu, MD, PhD, and Ma ´rio Vaisman, MD, PhD Abstract: Graves ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves disease, affecting between 25% and 50% of patients, mostly in a mild and self-limited manner. Three percent to 5% of cases need clinical or surgical treatment. Therapy options for mod- erate to severe GO include: local or systemic glucocorticoids, external orbital radiotherapy (OR), other immunosuppressants, plasmapheresis, intravenous immunoglobulin, somatostatin analogs, pentoxyphyline, and surgical orbital decompression. We have studied the long-term response of GO to intravenous pulses of methylprednisolone associated or not with OR in 21 patients with moderate to severe GO. Of these, 18 (86%) had a reduction in the clinical score and the remaining 3 showed no change to pulse therapy. The observed reduction in the clinical score was from an average of 3 to an average of one. Twelve patients (57%) exhibited a reduction in the degree of proptosis of more than 2 mm. Diplopia improved in 13 (93%) of the 14. Of these, 7 also received OR. All patients who were treated with OR and pulse therapy improved. Proptosis improved in 62% (5 patients) and diplopia improved in 75% (6 patients). We conclude that steroid pulse therapy, with or without OR, is a safe and effective treatment of GO. There were few adverse effects and quality of life was improved. Key Words: Graves ophthalmopathy, methylprednisolone, orbital radiotherapy (The Endocrinologist 2006;16: 193–196) G raves ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves disease, affecting between 25% and 50% 1–3 of patients, mostly in a mild and self-limited form. Ocular involvement can be subclinical with elevation of intraocular pressure even in the absence of exophthalmia or clinically apparent ophthalmopathy. 4 There are, however, severe and disfiguring forms that interfere with the quality of life of affected patients. Three percent to 5% of cases need clinical or surgical treatment. 5,6 GO can also affect patients with Hashimoto thyroiditis and euthyroid individuals with positive thyroid autoimmunity. 2,7 The pathogenesis of GO is not entirely clear. It is known that autoimmune inflammatory processes are associated with increased production of glycosaminoglycans, edema, fibro- blast proliferation, and adipogenesis. All of these increase the volume of orbital components. Myocyte involvement fol- lows. It is believed that there is at least one common antigen shared by the orbit and the thyroid that could initiate this process. The main candidates are the thyroid-stimulating hormone (TSH) receptor expressed in orbital fibroblasts and preadipocytes, G2s/FOXP1, flavoprotein, thyroglobulin, and the orbital acetylcholine receptor. 1,2,7–9 The main clinical findings of GO are proptosis, conjunc- tival edema, chemosis, an ocular burning sensation, visual blur- ring, tearing, photophobia, and dysfunction of the extrinsic ocular muscles leading to diplopia. Some patients exhibit a compressive ocular neuropathy which, rarely, can progress to visual loss. 8 GO can be classified as mild, moderate, or severe based on clinical parameters such as proptosis, optic neuropathy, and/or dysfunction of the extrinsic ocular muscles. Soft tissue involvement is more associated with activity than with sever- ity of the disease. The activity GO has 2 phases: an initial, inflammatory one, which can progressively worsen, and a second one, fibrotic, which is static and residual. Defining of the phase using clinical parameters, some imaging methods (such as ultrasound, mag- netic resonance, and OctreoScan), and/or urinary or serum de- terminations of glycosaminoglycans such as hyaluronan 10 are critical for determining the choice of therapy. GO tends to improve with the regression of hyperthy- roidism whatever the type of treatment. The use of radioio- dine can be associated with a transient worsening of GO. This can be prevented by the concomitant administration of pred- nisone. 11 Supportive therapy such as dark glasses, methylcel- lulose eyedrops, elevation of headrest, eye occlusion during sleep and, very important, the avoidance of smoking can be very helpful. These measures can be all that is necessary to effectively treat mild GO. Therapy options for moderate to severe GO include local or systemic glucocorticoids, external radiotherapy, im- From the Servic ¸o de Endocrinologia–Hospital Universita ´rio Clementino Fraga Filho/Faculdade de Medicina, Universidade Federal do Rio de Janeiro–UFRJ. Reprints: Ma ´rio Vaisman, MD, PhD, Rua General Vena ˆncio Flores, 368 Apto 302–Leblon, Rio de Janeiro, RJ, Brasil. E-mail: vaisman@hucff.ufrj.br. Copyright © 2006 by Lippincott Williams & Wilkins ISSN: 1051-2144/06/1604-0193 DOI: 10.1097/01.ten.0000227493.32959.ae The Endocrinologist • Volume 16, Number 4, August 2006 193