Abnormal Thyroid Peroxidase Causing Iodide Organification Defect

Abstract

The spectrum of familial goiter due to iodide organification defect includes goitrous cretins, Pendred's syndrome, and goiter with euthyroidism and normal hearing. One female example of the latter group, now age 16, with goiter since age 6 and 50% perchlorate discharge, underwent thyroidectomy. The thyroid tissue demonstrated lack of peroxidase activity in the tyrosine iodinase, triiodide, guaiacol, and p-hydroxyphenylpyruvic acid (HPPA) assays. An inhibitor,of doubtful significance, was detected in the tissue in both triiodide and guaiacol assays using a soluble bovine thyroid peroxidase as enzyme source. No inhibition was found in the tyrosine iodinase or HPPA assays. Preincubation of the inactive enzymatic preparation from the goiter with hematin restored activity in the tyrosine iodinase assay to normal levels, while activity in the triiodide assay remained negligible. Using other human thyroid peroxidase preparations as controls, it was observed that the reconstructed enzyme from the goiter was more labile to high concentrations of H2O2 than normal peroxidase enzyme. The most probable cause of the disease is a genetic alteration in the protein structure of the peroxidase that prevented normal in vivo binding of the prosthetic group with the apoenzyme present in the gland. Presumably some enzyme bound to the prosthetic group in a manner not specifically normal, but sufficient to maintain euthyroidism in the patient.