heparitin-sulfate and Myxedema

From three patients with pretibial myxedema (PTM) of Graves' disease, a portion of the skin involved was biopsied, analyzed for proteoglycans and the results were compared with those obtained with euthyroid and hyperthyroid subjects without PTM. The tissue specimen was extracted with 4 M guanidine HCl and subjected to subsequent CsCl density gradient centrifugation. Glycosaminoglycan and protein were recovered in the heaviest density fraction in the three specimens obtained from patients with PTM and not from subjects without PTM. From the analysis by Sepharose CL-6B column, glycosaminoglycan was present as a form of proteoglycan because alkaline borohydride treatment released single chain glycosaminoglycan with a molecular weight of 77,000 or 66,000. The digestion with chondroitin ABC lyase revealed that the majority of proteoglycan in the skin tissue was chondroitin sulfate or dermatan sulfate, and heparan sulfate comprised the minor component (14-34%). The rate of proteoglycan biosynthesis was examined by 35S incorporation into glycosaminoglycan's by cultured fibroblasts from PTM and normal skin. Incorporation of 35S into both proteoglycan and single chain glycosaminoglycan was observed in the fibroblasts of PTM patients as well as of those of subjects without PTM, although the rate of synthesis was more pronounced in the former. The rate of synthesis was influenced neither by normal serum or serum from a pretibial myxedema patient. Since proteoglycan accumulation was detected only in the affected skin of PTM patients, the impairment of local degradation and the proteoglycan clearance mechanism may also be involved.

Topics: Centrifugation, Isopycnic; Chondroitin Sulfates; Graves Disease; Heparitin Sulfate; Humans; Molecular Weight; Myxedema; Proteoglycans; Skin Diseases

We assessed skin accumulation of acid glycosaminoglycans in ten patients with primary myxoedema (median age 70 years) before and during l-thyroxine treatment (median 7 months). Eight subjects matched for sex and age served as controls. Acid glycosaminoglycans were determined biochemically on small skin biopsies. Hyaluronic acid was elevated in untreated myxoedema, median 0.60, range 0.39-0.90 microgram hexosamine/mg dried defatted tissue compared to a median control value of 0.52, range 0.43-0.65 microgram hexosamine/mg dried defatted tissue, P less than 0.02. Chondroitin-4,6-sulphate and dermatan sulphate showed no elevation, while heparan sulphate was actually reduced in myxoedema, P less than 0.01. l-thyroxine treatment induced a significant reduction in hyaluronic acid, median 0.41, range 0.24-0.71 microgram hexosamine/mg dried defatted tissue, while no consistent changes occurred in the remaining three acid glycosamine glycans. The accumulation of hyaluronic acid might contribute to the peculiar non-pitting oedema of the skin in myxoedema, due to the strong water-binding capacity of the substance.

Topics: Adult; Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Myxedema; Skin; Thyroxine

Acid glycosaminoglycans were measured in the tissues of a virtually untreated 83-year-old woman with myxoedema. Intercellular oedema was demonstrated histologically in the tongue, myocardium, striated muscles, and in the skin. Tissue oedema was absent in two female control patients. All tissues from the patient with myxoedema, apart from the stomach, showed high concentrations of hyaluronic acid, but there was no consistent elevation of chondroitin-4,6-sulphate, heparan sulphate or dermatan sulphate. The accumulation of hyaluronic acid might contribute to the oedema formation in myxoedema.

Topics: Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Myxedema; Tissue Distribution