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FAMILIAL THYROID PEROXIDASE DEFECT
Author(s) -
MEDEIROSNETO GERALDO A.,
OKAMURA KEN,
CAVALIERE HUMBERTO,
TAUROG ALVIN,
KNOBEL MEYER,
BISI HELIO,
KALLAS WALLACE G.,
MATTAR EMILIO
Publication year - 1982
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1982.tb02628.x
Subject(s) - medicine , endocrinology , guaiacol , thyroid peroxidase , thyroid , thyroglobulin , chemistry , perchlorate , iodine , iodide , biochemistry , organic chemistry , enzyme , ion
SUMMARY A congenitally goitrous, mentally retarded, hypothyroid child, whose parents were first cousins, was studied for the cause of a strongly positive (86–5%) perchlorate discharge test. The mother had a recidivant goitre after being thyroidectomized in 1971. Her perchlorate discharge test was negative, but she displayed an exaggerated TSH response to TRH administration. The father also showed a negative perchlorate discharge, but he had a large cold nodule in the left thyroid lobe. The father also presented with a retinitis pigmentosa, detected additionally in two of his brothers and three nephews. Thyroid tissue, obtained from the three patients at surgery, was assayed for thyroid peroxidase (TPO) by three different assays:1 iodination of goitre thyroglobulin; 2 oxidation of guaiacol; 3 oxidation of iodide.In a standard iodination assay (100 μM I − ) and in a standard guaiacol assay 4–7 mM guaiacol) the TPO activity in the son's tissue was extremely low. Preincubation with haematin did not restore activity. The father displayed a normal TPO activity, but that of the mother was somewhat low. In the iodide oxidation assay employing 12 mM I − in the incubation system, and in iodination and guaiacol assays employing elevated concentrations of substrate, the TPO activity in the son's tissue was quite appreciable and was much closer to that of the parents. Presumably, therefore, the defect in the son's thyroid did not involve an absence of TPO. Rather, the results suggest a qualitative defect in the son's TPO, involving an abnormality in the binding of substrate for oxidation. Thyroglobulin was isolated from the thyroid soluble fraction by sucrose density gradient centrifugation and its protein and iodine content determined. Thyroglobulin from the son's thyroid tissue contained only 0–043% iodine, compared to 0–45% and 0–29% for mother and father, respectively. The very low iodine content of the son's thyroglobulin accords with the low thyroid peroxidase activity and with the clinical and laboratory findings. The fact that the parents in the present study are first cousins and that both showed some type of thyroid abnormality suggests that the severely affected son (goitre, mental retardation, and hypothyroidism) is homozygous for a recessive mutant gene.