The Possible Occurrence of Two Inborn Errors of Iodine Metabolism in One Patient

Abstract

The occurrence of two separate inborn errors of iodine metabolism in one patient has been suggested by some authors but doubted by others. The combination of two other mechanisms may explain most of these cases: one defect may be conditioned by another, or the defects may have a common underlying cause. A seemingly impeded deiodination of iodotyrosines, found together with one of the other defects in a hypothyroid patient, may be an example of the first mechanism. The second mechanism might be involved when the primary abnormality is located in the biogenesis of thyroglobulin. In the absence of normal thyroglobulin, three successive reactions could secondarily be influenced: the iodination, the »coupling« and the proteolysis. Thus, when two or more of these reactions are found to be (partially) blocked, defective thyroglobulin biogenesis should be considered as a possibility. A case is presented in which such a defect was at first suggested by the simultaneous occurrence of circulating iodinated protein-like compounds (defective proteolysis) and the secretion of large amounts of iodide by the thyroid (hampered coupling), and was subsequently confirmed by the electrophoretic analysis of a thyroid extract which showed an absence of normal thyroglobulin. Furthermore, additional evidence is presented on a similar patient described in a previous paper. Finally, a survey is given of sixteen other patients described in the literature in whom the existence of defective thyroglobulin biogenesis was either suggested by the occurrence of two seemingly separate defects or confirmed by the absence of normal thyroglobulin.

Studies on Mono- and Diiodohistidine. II. CONGENITAL GOITROUS HYPOTHYROIDISM WITH THYROGLOBULIN DEFECT AND IODOHISTIDINE-RICH IODOALBUMIN PRODUCTION

“…c Firstly, the high radioiodide uptake, the negative perchlorate discharge test, the detection of an iodotyrosine edeiodinase activity eliminate other syndromes except afor the rare occurrence of associated defects (3,10).…”

“…This iodoalbumin has ialso been identified from the serum of the patients (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). From the poorly iodinated iodoalbumin, low peptide-linked levels of hormone were already reported (8,11).…”

“…An iodoalbumin has been identified in similar goiters (6), and thyroglobulin has been reported as reduced (3)(4)(5)7) or apparently absent (2,(8)(9)(10)(11). From similar patients, other butanol-insoluble compounds were detected either in thyroid (2,4,7) or serum (1,4,8) hydrolysates, and in urines (2,3,10,11). These compounds, constituting the butanol-insoluble iodine (BII)' moiety of the urine, were not identified.…”

A Goitrous Subject with Structural Abnormality of Thyroglobulin

“…This could eliminate the possibility of even a partial defect in an enzyme or enzymes as an inborn error of thyroid hormone biosynthesis in this case, although a defect in any other iodinating or iodideoxidizing mediator than peroxidase could not be excluded. Wiener and Lindeboom (27) have postulated that the existence of defective thyroglobulin biosynthesis is suggested by the occurrence of two seemingly separate defects in thyroid hormone production. In Patient D, iodide organification defect and refractoriness of thyroglobulin to proteolytic enzyme were observed.…”