SKIN FIBROBLAST ACTIVITY IN PRETIBIAL MYXEDEMA AND THE EFFECT OF OCTREOTIDE (SANDOSTATIN(R)) IN-VITRO

The accumulation of glycosaminoglycans in the skin in pretibial myxoedema appears to be a response by local fibroblasts to a stimulating factor in the patient's serum, but the identity of the factor, its ability to stimulate skin fibroblasts as opposed to cultured thyroid cells, and the specificity of its effect to pretibial skin fibroblasts, are all controversial. We have studied fibroblasts cultured from the lesional skin of two women with pretibial myxoedema, and compared their proliferation and secretion of glycosaminoglycans with those of fibroblasts from the patients' forearms and from the forearm skin of two normal subjects. We found that in the presence of the patients' sera all six lines of fibroblasts secreted more glycosaminoglycans [205 +/- 21% (SD)] than with normal human sera (147 +/- 19%), or fetal calf serum (100%). Fibroblast proliferation showed the same pattern of differences: patients' sera 142 +/- 22%; normal human sera 116 +/- 9%, and fetal calf serum 100%. These experiments confirm the presence of a serum factor in pretibial myxoedema which is capable of stimulating the activity of skin fibroblasts in vitro, and show that its effects are not restricted to fibroblasts from pretibial skin or to those grown from the skin of the patients. Proliferation of normal fibroblasts cultured in medium supplemented with fetal calf serum was reduced by Sandostatin(R) (octreotide), but it failed to inhibit their secretion of glycosaminoglycans. In contrast, secretion of glycosaminoglycans by a patient's pretibial skin fibroblasts was almost completely inhibited by 1 mM minoxidil. In the presence of patients' sera Sandostatin(R) (0.1-10 mu g/ml) reduced secretion of glycosaminoglycans by about 50%. Our data support the use of Sandostatin(R) in pretibial myxoedema, and suggest that it may suppress fibroblast glycosaminoglycan secretion within the skin via depletion of insulin-like growth factor or the blocking of its effect.