Abstract
A 36-year-old male with congenital goitrous hypothyroidism is presented. Thyroidal iodide was released by Perchlorate (62%) indicating a iodide organification defect. Serum T4 was 0.8 μg/dl, T3 was 16 ng/dl and TSH level 190 μU/ml. Tests for autoantibodies against thyroid antigens were negative. Chromatographs of serial serum samples after a tracer dose of 125I indicated only the presence of iodoalbumin (48.5%). At surgery the gland weighed 1,680 g and histologically the tissue showed marked heterogeinity. Total iodide content of the thyroid was very low (3.4 μg of l/g of tissue). The iodothyronines comprised only 8.1% of the iodocompounds in the pronase-digested homogenate of the gland, and the major components were the iodotyrosines (82.6%) with a very high DIT/MIT ratio (3.6). Enzymatic studies performed on the tissue demonstrated very low peroxidase activity (7–15% of normal values) according to results in the triiodide, guaiacol and tyrosine iodinase assays. Preincubation of the enzyme with hematin did not increase peroxidase activity. Catatase activity was normal and cytochrome c reductase, a possible source of endogenous thyroidal H2O2, was also within the normal range. Peroxidase was normally present in the saliva and in peripheral leucocytes. Thyroglobulin (Tg) was found to be the major soluble protein component of the homogenate although the iodine content of Tg was markedly reduced (0.16%). It is suggested that the congenital absence of peroxidase in this patient causes an organification block and also possibly impairs the coupling reaction within the thyroglobulin molecule.
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Hagen G.A., Niepomniszcze H., Haibach H., Bigazzi M., Hati R., Rapoport B., Jimenez C., DeGroot L.J., Flawley T.F. Peroxidase deficiency in familial goiter with iodide organification defect. N. Engl. J. Med. 285: 1394, 1971.
Niepomniszcze H., Castells S., DeGroot L.J., Refetoff S., Kim O.S., Rapoport B., Hati R. Peroxidase defect in congenital goiter with complete organification block. J. Clin. Endocrinol. Metab. 36: 347, 1973.
Niepomniszcze H., DeGrossi O., Scavini L.M., Curutchet H.P. Familial goiter with partial iodine incorporation block and euthyroidism due to the deficient peroxidase defect. In: Robbins J. and Braverman L.E. (Eds.), Thyroid Research. Excerpta Medica, Amsterdam, 1976, p. 470.
Valenta L.J., Bocle H., Vichery A.L., Caulfield J.B., Maloof F. Lack of thyroid peroxidase activity as the cause of congenital goitrous hypothyroidism. J. Clin. Endocrinol. Metab. 36: 830, 1973.
Niepomniszcze H., DeGroot L.J., Hagen G.A. Abnormal thyroid peroxidase causing iodide organification defect. J. Clin. Endocrinol. Metab. 34: 607, 1972.
Niepomniszcze H., Rosenbloom A.L., DeGroot L.J., Shimaoka L., Refetoff S., Yamamoto K. Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism. Metabolism 24: 57, 1975.
Pommier J., Tourniaire J., Dème D., Chalendor D., Bornet H., Nunez J. A defective thyroid peroxidase solubilized from a familial goiter with iodine organification defect. J. Clin. Endocrinol. Metab. 39: 69, 1974.
Kusakabe T. Deficient cytochrome b5 reductase activity in nontoxic goiter with iodide organification defect. Metabolism 24: 1103, 1975.
Pommier J., Dominici R., Bougneres P., Rahmoun B., Nunez J. A dialysable inhibitor bound to thyroglobulins from four simple goiters and from two goiters with iodine organification defect. J. Molec. Med. 2: 169, 1977.
Medeiros-Neto G.A., Kieffer J., Nicolau W., Ulhôa-Cintra A.B. Plasma chromatography of iodinated compounds in cryptothyroidism. J. Clin. Endocrinol. Metab. 27: 1053, 1967.
Niepomniszcze H., Medeiros-Neto G.A., Refetoff S., DeGroot L.J., Faug V.J. Familial goiter with partial iodine organification defect, lackofthyroglobulinand high levels of thyroid peroxidase. Clin. Endocrinol. (Oxf.) 6: 27, 1977.
Yamamoto K., DeGroot L.J. Peroxidase and NADPH-cytochrome c redutase activity during thyroid hyperplasia and involution. Endocrinology 96: 1022, 1975.
Taurog A. Thyroid peroxidase and thyroxine biosynthesis. Recent Prog. Horm. Res. 26: 189, 1970.
Kusakabe T. A goitrous subject with structural abnormality of thyro-globulin. J. Clin. Endocrinol. Metab. 35: 785, 1972.
Kusakabe T. A goitrous subject with defective synthesis of diiodotyro-sine due to thyroglobulin abnormalities. J. Clin. Endocrinol. Metab. 37: 317, 1973.
Lizzaralde G., Jones B., Seal U.S., Jones J.E. Goitrous cretinism with chromosomal aberration and defect in thyroglobulin synthesis. J. Clin. Endocrinol. Metab. 26: 1227, 1966.
Ljunggren J.G., Lindström H., Hjern B. The concentration of peroxidase in normal and adenomatous human thyroid tissue with special reference to patients with Pendred’s syndrome. Acta Endocrinol. (Kbh.) 72: 272, 1973.
Michel R., Rall J.E., Roche J., Tubiana M. Thyroidal iodoproteins in patients with goitrous hypothyroidism. J. Clin. Endocrinol. Metab. 24: 352, 1964.
Mouriz J., Riesco G., Usobiaga P. Thyroid proteins in a goitrous cretin with iodide organification defect. J. Clin. Endocrinol. Metab. 29: 942, 1969.
Cave W.T. Jr., Dunn J.T. Studies on the thyroid defect in an atypical form of Pendred’s syndrome. J. Clin. Endocrinol. Metab. 41: 590, 1975.
Lissitzky S., Bismuth J., Jaquet P., Castay J., Michel-Bechet M., Koutras D.A., Pharmakiotis A.D., Moschos A., Psarras A., Malamos B. Congenital goiter with impaired thyroglobulin synthesis. J. Clin. Endocrinol. Metab. 36: 17, 1973.
Lissitzky S., Codaccioni J.L., Bismuth J., Depieds R.C. Congenital goiter with hypothyroidism and iodo-serum albumin replacing thyroglobulin. J. Clin. Endocrinol. Metab. 27: 185, 1967.
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Medeiros-Neto, G.A., Knobel, M., Yamamoto, K. et al. Deficient thyroid peroxidase causing organification defect and goitrous hypothyroidism. J Endocrinol Invest 2, 353–357 (1979). https://doi.org/10.1007/BF03349333
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DOI: https://doi.org/10.1007/BF03349333