A Goitrous Subject with Structural Abnormality of Thyroglobulin

Abstract

This report consists of a study of a woman with goiter whose primary defect seems to be in an abnormal stereostructure of thyroglobulin. She showed a positive thiocyanate discharge of 131 I by the thyroid. Activities of thyroid peroxidase, catalase, transaminase, keto-enol tautomerase, and protease were comparatively normal. 126 I-labeled monoiodotyrosine injected into the patient was rapidly deiodinated. Since the iodine content of the goiter thyroglobulin was at a high normal level (0.78%), it is unlikely that an iodide organification defect is a primary abnormality in this case. The behavior of the thyroid protein obtained from the patient was indistinguishable from that of normal thyroglobulin in solubility, electrophoretic mobility, sedimentation velocity, and antigenicity. Spectrotitration of tyrosyl and iodoamino acid residues in native and in vitro iodinated goiter thyroglobulin was performed in water and in 8M urea, and the reactivity of these residues was assessed with N-acetyl imidazole. Although the sum of the aromatic groups in tyrosyl and iodoamino acid residues in goiter thyroglobulin determined in 8M urea was equal to that in normal thyroglobulin, about two-thirds of tyrosyl and monoiodotyrosyl residues, and the majority of diiodotyrosyl and thyroxyl residues, appeared to be strongly buried inside the protein molecule, since these were not demonstrated in water. The number of tyrosyl residues that were easily accessible to iodide was about one-third of that in normal thyroglobulin. The percent of radioiodine bound to the goiter thyroglobulin by in vitro peroxidation also was one-third of that bound to the normal thyroglobulin. In vivo labeled goiter thyroglobulin proved to be resistant to the liberation of 1 2 5 I from the results of its hydrolysis with protease.

Biochemical Studies on the Iodine Organification Defect of Pendred's Syndrome

“…It has been postulated that congenital goitre due to failure of normal iodide organification could be a consequence of a defect in one or more components of the iodination system . Evidences for the occurrence of several types of peroxidase defects (Niepomniszcze et al 1972(Niepomniszcze et al , 1973(Niepomniszcze et al , 1975V'alenta et al 1973;Pommier et al 1974Pommier et al , 1976, possible abnormal H9O9 sources (Niepomniszcze 1976;Knsakabe 1975), and altered thyroglobulin producing organification block Kusakabe 1972Kusakabe , 1973, has been presented in the past few years. Ljunggren et al (1973) were the first to demonstrate normal thyroid pe¬ roxidase activity in patients with Pendred's syndrome.…”

Serum thyroglobulin (Tg) stimulation with bovine TSH: a useful test for diagnosis of congenital goitrous hypothyroidism due to defective Tg synthesis

“…Abnormalities of Tg synthesis and secretion may be related to quantitative or qualitative abnormali¬ ties in Tg mRNA or DNA (Von Voorthuizen et al 1978), the cellular transport of Tg to the apical site of the cell (Lissitzky et al 1975) or defective glycosylation (Kusakabe 1972). These defects have been described both in animals and man ) and the most important screening test in this group of disorders is simultaneous serum chemical measurement of protein bound iodide (PBI) and thyroxine iodine by radioimmunoassay.…”

Congenital goitre due to "thyroid peroxidase-iodinase defect"

“…Moreover, a patient whose peroxidase was inactive in crude preparatiorjs, but normal after true solubilization, was studied by Pommier et al (1974). Other cases, with impaired organifica¬ tion of iodine, were reported as having abnormal thyroglobulin (Kusakabe 1972(Kusakabe , 1973Niepom¬ niszcze et al 1977) or defective H2O2 supply (Kusa¬ kabe 1975;Niepomniszcze 1976 In this report we present biochemical studies performed on the thyroid of a patient with con¬ genital goitrous cretinism with an almost complete discharge of radioiodide during the perchlorate test. The main finding was a qualitative abnormal thyroid peroxidase that was unable to iodinate tyrosine.…”