Mild familial goitrous hypothyroidism associated with prolonged 131-iodine retention: possible defect in thyroglobulin synthesis

Four male siblings presented with goitrous hypothyroidism which had been presentfrom the first few years of life. Serum total tyroxine (T4), free T4 index and free T4 levels were low or in the low-normal range while TSH levels were elevated; triiodothyronine (T3) levels were normal. The 131-I-uptake was elevated at 4 and 24 h, 76–93% and 69–82% respectively (normal less than 50%), and remained elevated 96 h after the administration of radioiodine. Administration of potassium perchlorate did not cause a reduction in thyroidal radioiodine. These findings, therefore, were not consistent with defects affecting iodine trapping, iodine organification or iodotyrosine deiodinase. If a coupling defect was the cause of the disorder, iodotyrosines would have to cycle between the thyroid cell and thyroglobulin in the follicular lumen undergoing deiodination, and reorganification continually. To examine this possibility carbimazole, which inhibits organification of iodine was taken orally following administration of 131-I; potassium perchlorate was given to discharge any accumulating nonorganified radioiodine. 131-I uptake changed only from 50 to 48% and from 68 to 71% in the 2 subjects studied. These findings do not support a coupling defect. The possibility of abnormal thyroglobulin synthesis was supported by the finding of inappropriately low serum thyroglobulin levels. A specimen of thyroid tissue demonstrated a 40-fold reduction in normal thyroglobulin content. These findings suggest that our sibship have a rare partial defect in thyroglobulin synthesis and that iodine is incorporated into an alternative complex which is resistant to mobilization.