Refractory pretibial myxoedema with response to intralesional insulin-like growth factor 1 antagonist (octreotide): downregulation of hyaluronic acid production by the lesional fibroblasts

We report a case of refractory pretibial myxoedema (PTM) with Graves' disease in which there was a good clinical response to intralesional injection of the insulin-like growth factor 1 (IGF-1) antagonist octreotide. Intralesional octreotide (200 mug once daily) dramatically improved the tumorous lesions of PTM after 4 weeks, and the lesions remained stable even after reducing the dose to 200 mug once weekly. The amount of hyaluronic acid (HA) in the lesional skin decreased to 5.8 mug mg(-1) dry weight from 16.3 mug mg(-1) dry weight after 4 weeks of octreotide treatment. IGF-1 showed a dose-dependent stimulatory effect on HA secretion by both normal and patient's fibroblasts at higher concentrations in vitro. Octreotide significantly suppressed IGF-1 induced-HA secretion by the patient's fibroblasts, but not by normal fibroblasts, which suggests that expression of IGF-1 receptor on fibroblasts, or its affinity for IGF-1, are upregulated in PTM, resulting in the oversecretion of HA. These results might suggest that octreotide improves PTM through downregulation of HA production by lesional fibroblasts.