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Endocrine Abstracts (2011) 25 CM1.3

University of Insubria, Varese, Italy.


Extrathyroidal manifestations of Graves’ disease include eye disease (Graves’ ophthalmopathy, GO), dermopathy (also known as pretibial myxedema) and nail changes (acropachy). While about 50% of Graves’ patients are affected with mild to moderately severe GO, dermopathy is present only in 1–4% of cases, and acropachy in 0.1–0.4%.

Management of GO represents a complex and unresolved problem, and the treatment outcome is frequently unsatisfactory both to the patient and the physician. Medical treatment is often followed by rehabilitative surgery, including orbital decompression, squint surgery, eyelid surgery. An aggressive medical treatment is indicated only when GO is active, i.e. in the inflammatory phase of the disease. Mild active GO usually does not require a specific treatment but only local measures such as artificial tears, ointments, dark lenses, prisms (for mild diplopia), and general measures, such as refrain from smoking. If however the quality of life is severely affected, the patient can be admitted to active treatment as for moderate-to-severe cases. First-line treatment for moderate-to-severe and active GO is represented by glucocorticoids. The latter can administered via the oral route or the i.v. route. Randomized clinical trials have shown that the i.v. route is more effective and, in general, better tolerated. Severe side effects may however occur. Accordingly, this treatment should preferably be performed in specialized centres under strict surveillance. There is no evidence as to the optimal regimen. A commonly used schedule consists of 12 weekly slow infusion, with a cumulative dose of 4.5–5 g methylprednisolone. Some evidence suggests that a cumulative dose <8 g per cycle is associated with a low risk of hepatotoxicity. Unfortunately, treatment outcome is not always favourable. If response is not satisfactory and GO is still active, treatment options include a second course of i.v. glucocorticoids associated with orbital radiotherapy, or oral glucocorticoids combined with cyclosporine. A promising drug for GO (and Graves’ hyperthyroidism) is rituximab, but randomized clinical trials on the use of this drug are lacking. In cases of sight-threatening GO (mostly due to dysthyroid optic neuropathy), i.v. methylprednisolone at very high doses (1 g for three consecutive days, to be repeated on the next week) is the first-line treatment. If the response is absent or poor within 2 weeks, the patient should be promptly submitted to orbital decompression. Rehabilitative surgery, if needed, should be performed after GO has been inactive for at least 6 months. If more than one operation is required, orbital decompression, squint surgery and eyelid surgery should be performed in this sequence.

Dermopathy usually occurs in patients who also have severe GO. In mild-to-moderate forms topical steroid ointment with sealing cover (steroid occlusive dressing technique) for at least 4–6 weeks is the treatment of choice, but the long-term benefit of this treatment remains to be clearly determined. Systemic glucocorticoids are rarely employed, unless they are used for the concomitant GO. High-dose i.v. immunoglobulins, octreotide and plasmapheresis have occasionally been used for severe cases of dermopathy with some success, but evidence on the real effectiveness of these treatments is scant. Surgical excision has been reported in elephantiasic forms of dermopathy, but it is usually not recommended because of the high recurrence rates.

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