Protein-Linked Iodotyrosines in Serum after Topical Application of Povidone-Iodine (Betadine)

Abstract

Markedly elevated serum PBI levels occur after therapy with povidone-iodine (Betadine), an iodine-polyvinylpyrrolidone iodophor. In this study, we investigated the serum iodine compounds from a severely burned patient with normal initial thyroid function tests who was swabbed with Betadine ointment and received daily therapeutic baths in Betadine. Three and 9 days after therapy, his serum contained 93 and 168 micrograms PGI/dl, respectively (normal range, 4-8), while the serum T4 and free T4 index were normal; the serum T3 level, however, was abnormally depressed. Most of the PBI was in albumin, and hydrolysis of the serum proteins with proteases released 35% of the PBI as monoiodotyrosine, 3.2% as diiodotyrosine, 0.01% as T3, and 2.5% as T4, as determined by competitive radioassays, anion exchange, and reversed phase high pressure liquid chromatography. The same concentrations of T4 and T3 were detected before and after hydrolysis. Failure of the proteases to completely hydrolyze iodoalbumin partially explains why all of the PBI was not recovered as iodotyrosines in the serum protein hydrolysates. Povidone-iodine rapidly iodinated tyrosine residues in human serum albumin at pH 7.4 and 37 C in vitro, and the ratio of diiodotyrosine to monoiodotyrosine increased as the molar ratio of povidone-iodine to albumin was increased. It is concluded that the abnormal increase in serum PBI resulted from absorption of the iodophor into the blood where it primarily iodinated albumin and, to a lesser extent, the globulins.