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 microg once daily) dramatically improved the tumorous lesions of PTM after 4 weeks, and the lesions remained stable even after reducing the dose to 200 microg once weekly. The amount of hyaluronic acid (HA) in the lesional skin decreased to 5.8 microg mg-1 dry weight from 16.3 microg 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.
Shinohara
M
M
Department of Dermatology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8102, Japan.
Hamasaki
Y
Y
Katayama
I
I
D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D007868:Leg Dermatoses / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009230:Myxedema / Q000188:drug therapy*; D015282:Octreotide / Q000627:therapeutic use*
D006728:Hormones; D007334:Insulin-Like Growth Factor I; D006820:Hyaluronic Acid; D015282:Octreotide