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Cigarette Smoking and Treatment Outcomes in Graves Ophthalmopathy

Luigi Bartalena, MD; Claudio Marcocci, MD; Maria Laura Tanda, MD; Luca Manetti, MD; Enrica Dell'Unto, MD; Maria Pia Bartolomei, MD; Marco Nardi, MD; Enio Martino, MD; and Aldo Pinchera, MD
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From the University of Pisa, Pisa, Italy. Grant Support: In part by grants from the University of Pisa (Fondi di Ateneo), Pisa, Italy, and from Ministero della Universita e della Ricerca Scientifica e Tecnologica (40% funding), Rome, Italy. Requests for Reprints: Luigi Bartalena, MD, Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Ospedale Cisanello, via Paradisa, 2, 56122 Pisa, Italy; e-mail, l.bartalena@endoc.med.unipi.it. Current Author Addresses: Drs. Bartalena, Marcocci, Tanda, Manetti, Dell'Unto, Martino, and Pinchera: Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Ospedale Cisanello, via Paradisa, 2, 56122 Pisa, Italy.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1998;129(8):632-635. doi:10.7326/0003-4819-129-8-199810150-00010
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Background: It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes.

Objective: To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Graves ophthalmopathy receiving orbital radiation therapy and glucocorticoids.

Design: Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2).

Setting: University medical center.

Patients: 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2).

Intervention: In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks).

Measurements: Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy).

Results: In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001).

Conclusions: Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy.

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