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Medical Therapy

Medical Therapy

Medical therapy is offered during the early active or progressive phase of TED:  the intention is to block specific steps in the immune-mediated, inflammatory process to reduce ultimate collateral damage to orbital tissues.

Gluco-corticosteroids (GC)

These remain the first choice for active TED with significant congestive or inflammatory signs. They may reverse DON, although this may be incomplete or temporary so that adjunctive radiotherapy or surgical decompression may be necessary. They also are recommended preventively to avoid exacerbation of active TED at time of radioactive iodine thyroid ablation.


Standard oral therapy is daily prednisone 0.5–1.0 mg/kg daily for 6 weeks, but this route has side effects in 50% of cases, including Cushing’s syndrome, diabetes mellitus, insomnia, mood disturbances, gastric ulcers, osteopenia, necrosis of the femoral head, and susceptibility to infections.


Intravenous GC therapy reduces the incidence of side effects and allows a longer duration of therapy. A popular protocol is IV methylprednisolone 500 mg weekly for 6 weeks, reducing to 250 mg weekly for 6 weeks. This author prefers to titrate the dose or prolong the intervals depending on clinical response. Liver failure and rare cases of death have been reported in cumulative doses over 8 g of methylprednisolone.


Depot GC injection into the inferolateral orbital fat pocket is beneficial for focal orbital congestion but carries a small risk of intravascular emboli with visual loss.


Retrospective studies find efficacy of 60% overall for oral GC and 85% for IV GC in reducing inflammatory features in active TED. The effect occurs within 24 hours but is short-lived, so prolonged therapy is required (Fig. 12.13.6). A recent large series from Vancouver found that although appropriate doses of GC effectively reduced inflammatory scores, 17% of patients in the high-risk muscle-targeted group developed DON and 35% had worsening of diplopia or ocular restriction. In a comparable group in which combined GC and radiotherapy was provided, none developed DON, and improved diplopia and motility scores were observed.


Cyclosporine combined with CS enhances its benefit against inflammatory soft tissue changes.Intravenous immunoglobulin (IVIg) therapy is reported to be as effective as oral GC with a low rate of adverse effects but is expensive.


This oral antioxidant mineral is found in Brazil nuts, tuna, and dark green leafy vegetables. A EUGOGO randomized controlled study in patients with mild TED found greater improvement in lid retraction, CAS, and QOL scores in those supplemented with selenium 100 µg twice daily compared with a placebo group after 6 months of therapy and 6 months after cessation of the drug. No adverse effects were identified. This study was conducted in countries with selenium-deficient diets, so a follow-up study is planned by ITEDS for North America, where selenium dietary levels are adequate.

Rituximab (RTX)

This anti-CD20 chimeric monoclonal antibody induces transient B-cell depletion and blocks early B-cell and T-cell activation. Small case series have found benefit in reducing CAS scores in cases refractory to GC. Two recent randomized controlled trials have studied the use of rituximab for moderately severe, active TED. The Mayo Clinic study randomized 25 participants into infusions of either RTX or saline. Both groups improved over a year follow-up with no significant difference noted between CAS or QOL scores. A study by Salvi et al. (n = 32) found RTX given either as two biweekly 1000-mg infusions or as a single 500-mg infusion was better at reducing CAS scores compared with IVCS (methylprednisolone 7.5 g total). The inactivation rate (defined as a reduction of CAS to 3) at 24 weeks was 100% in the RTX group and 69% in the IVCS group (P < 0.04). The different findings may relate to earlier treatment in the successful study. 


Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor. A randomized controlled study divided 32 active TED patients resistant to IVCS into groups either treated with tocilizumab or placebo at 0, 4, 8 and 12 weeks and found that a drop of 2 or more points in CAS was found in 93% of the treated group compared with 59% in the placebo group.  Significant side effects include gastrointestinal ulcers and respiratory infections in up to 10% of individuals. Subcutaneous delivery is possible and may have fewer complications.


Teprotumumab is an IGF1-R inhibitor without agonist effects.  A  randomized double-blind trial randomized 83 patients with active TED to receive 8 infusions of Teprotumumab or placebo every three weeks. At 24 weeks, the treated group showed significantly better primary outcomes (reduction in proptosis) as well as secondary outcomes of CAS, diplopia scores, and GO-QOL scores. Side-effects include diabetes mellitus and deafness.  The drug has yet to be compared with currently available therapies such as IVCS or for its effectiveness in CS failures.  It is costly therapy and is not yet available in many countries.