Lack of Thyroid Peroxidase Activity as the Cause of Congenital Goitrous Hypothyroidism

Abstract

Studies have been performed on a 52-yr-old female who presented with a goiter, mental deficiency, normal hearing, a serum T₄ = 1.0 μg per 100 ml, F T₄ = 0.4 ng per 100 ml, total T₃ 40 ng per 100 ml, BEI = 1.6 μg per 100 ml, BII 0.4 μg per 100 ml and a serum TSH of 82 μU/ml. The sella turcica was enlarged. The thyroid of the patient had a normal concentration mechanism for iodide; the peak uptake of ¹³¹I occurred at 4 hr (17%) and declined to 6.0% in 24 hr. Thiocyanate discharged 68% of the accumulated iodide in 1 hr and 84% in 3 hr. A tissue specific lack of peroxidase activity was found as assessed by the complete failure of thyroid tissue, in vitro, to peroxidize guaiacol, iodinate bovine serum albumin or to oxidize thiocyanate. The addition of hydrogen peroxide (10⁻⁴m) or hematin (10⁻⁴m) failed to stimulate peroxidase activity. Catalase activity was not excessive. Thyroglobulin was present and could be iodinated in the presence of H₂O₂ and horseradish peroxidase. Salivary peroxidase activity was present and there was no clinical evidence for the lack of myeloperoxidase activity. Normal deiodinase activity was present in the thyroid, evidence that this enzymatic activity is different from the peroxidase activity. Electron microscopic studies revealed normal appearing mitochondria, a marked increase in the rough endoplasmic reticulum and a decrease in the Golgi profiles.