Thyroxine Biosynthesis in Human Goitrous Cretinism1

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Abstract
Three adult goitrous cretin siblings were studied to determine the biochemical deficiency that resulted in depressed thyroidal thyroxine biosynthesis. Their thyroids could effectively transport and oxidize iodide and iodinate and deiodinate iodotyrosines. The glands had an adequate content of proteolytic enzymes for the release of free iodoamino acids. Thsse patients had a defective mechanism for synthesizing iodothyronines although there were no deficiencies in 2 enzymes, peroxidase and iodotyrosine transaminase, which have been implicated in the so-called coupling reaction. The serum protein bound iodine was normal but only ⅓ of this iodine was soluble in butanol, indicative of an abnormal iodopeptide or iodoprotein in the serum. Analysis of the iodoprotein composition of the cretin glands by salt fractionation, DEAEcellulose chromatography, radioimmunoelectrophoresis and sucrose gradient centrifugation revealed that there were only small amounts of thyroglobulin in the tissue. Some iodine was covalently linked as monoiodotyrosine and diiodotyrosine to proteins that were antigenically identical with human serum albumin. It appeared that the defect in these cretins was due to a deficiency in the synthesis of thyroglobulin.

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