Low molecular weight thyroglobulin leading to a goiter in a 12-year-old girl

We characterized the abnormal thyroglobulin (TG) in the thyroid and serum of a 12-yr-old girl with a large sporadic multinodular goiter first noted at age 4 yr. She developed normally and had no clinical evidence of hypothyroidism. However, her serum T4 was less than 1.0 microgram/dl, T3 was 125 ng/dl, and TSH was 155 microU/ml. Serum PBI was 9.7 micrograms/dl, and more than 90% was not extractable with butanol. The 24-h radioactive iodine uptake was 55%, not dischargeable by perchlorate. Hormone formation was tested by the administration of 131I before surgery. [131I]T4 and [131I]T3, but not 131I-labeled iodotyrosines, were present in the thyroidal venous blood. Hydrolysis of 10,000 X g supernatants from three randomly obtained samples of the goiter revealed 66-77% of the 131I as iodotyrosines, 2-4% as iodothyronines, and 10-12% as undigestable material; the MIT to DIT ratio ranged from 3.1-8.7, and the T4 to T3 ratio ranged from 2.3-8.3. The TG level was 2.5 mg/g in the goiter and 9.4 micrograms/ml in the serum. The RIA displacement curves for the goiter and serum TG levels were both identical to the curve produced by normal human TG. The iodine contents of goiter and serum TG were 0.49% and 0.47% (wt/wt), respectively. The T4 to T3 ratio was lower in the goiter (approximately 5) than in the serum iodoprotein (approximately 45), whereas the calculation of the T4 to T3 ratio in the thyroidal secretion was less than 1. The goiter and serum TG bound normally to Concanavalin A, indicating that they contained carbohydrate. When either serum- or goiter-soluble proteins were gel-filtered (Bio-Gel A-5m), TG immunoreactivity and stable iodine elution profiles were the same, suggesting that no significant amounts of other iodoproteins were present in the thyroid or circulation. Both serum and goiter TG elution volumes corresponded to mol wt of approximately 9 X 10(4). A sedimentation rate of 10-11 S was found for both goiter and serum TG. An abnormally low mol wt of 8.5-9.0 X 10(4) was determined by sodium dodecyl sulfate-electrophoresis, in good agreement with the estimates from gel filtration studies. A single band was present on sodium dodecyl sulfate-electrophoresis regardless of whether the TG was reduced before the analysis. Thus, it is very unlikely that the low molecular weight was due to partial hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS)