Studies on the thyroidal defect in an atypical form of Pendred's syndrome.

A 52-yr-old woman and her 47-yr-old brother both had large goiters, short stature, nerve deafness, and mild intellectual impairment. Serum levels of thyroid hormones were normal (sister) on borderline low (brother), urinary 127I levels were normal, and perchlorate discharge tests were negative. After adminstration of 125I, we found normal uptakes and retention of istotope by the thyroid, normal serum half-lives for PB 125I, and absence of labelled iodotyrosines in serum or urine. Particulate fractions from both glands had peroxidase activity by in vitro tests for guaiacol oxidation and tyrosine iodination. Samples from different parts of the sister's gland showed a correlation between peroxidase activity in vitro and radioiodine uptake in vivo. We made three separate preparations of thyroglobulin from the sister and one from the brother by gel filtration on 4% agarose. These were similar to each other and to thyrolobulin samples from normal humans when examined by gel electrophoresis both before and after reduction and alkylation. However, the three thyroglobulins from the same gland differed significantly from one another in their composition of most amino acids. This finding indicates that there can be heterogeneity in the protein portion of thyroglobulin, and since the three samples of thyroglobulin were from the same individual, this heterogeneity was probably not of genetic origin. In these patients we could not demonstrate any of the well-established biochemical defects associated with familial goiter. An abnormality in thyroglobulin structure remains in distinct possibility, but we must defer conclusions until there is more known about thyroglobulin heterogeneity and its relationship to hormone biosynthesis.