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GO is governed by complex pathogenic mechanisms. A number of drug interferences with these pathways have been described, resulting in clinically visible modifications of the disease process.

Antidiabetic thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands known to stimulate adipogenesis. The expression of PPAR-γ was significantly increased in orbital tissue samples from patients with GO compared with normal orbital tissue [21]. According to case reports and cohort studies, TZDs can worsen GO and trigger proliferative proptosis in isolated cases without thyroid dysfunction [22]. On the other hand, PPAR-γ agonists suppress TGF-β-induced hyaluronan biosynthesis in human orbital fibroblasts and exert antifibrotic and anti-inflammatory activity [23]. Complexity of PPAR-γ activation and orbital fibroblast heterogeneity might explain divergent responses to TZD administration, and further research is needed to select PPAR-γ activities to benefit GO.

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used in the treatment of multiple sclerosis. Up to 30% of the treated patients develop thyroid autoimmunity, and several cases of mild-to-moderate GO have been described [24]. Dysbalance of regulatory T cells, increased IL-21 receptor-positive effector T cells, and depletion of intrathyroid natural killer cells after alemtuzumab are presumably involved.

Lithium carbonate is the most common drug used for treating bipolar disorder. Lithium may induce both hypothyroidism and thyrotoxicosis by several mechanisms including triggering of autoimmunity with resultant thyroiditis, abnormal iodine kinetics, Jod-Basedow-like phenomenon, and direct toxicity to thyroid follicles resulting in release of thyroglobulin [25]. GO improvement after lithium withdrawal is a rare finding [26].

Patients treated with IFN-α, mostly for hepatitis C, may develop hypo- or hyperthyroidism and GO [27]. Thyroid antibodies in this group of patients occur in 40% and clinical thyroid disease in 15%. Management of GO cases could be difficult if liver dysfunction does not allow steroid or antithyroid medication use.