HEREDITARY CONGENITAL GOITRE WITH THYROGLOBULIN DEFICIENCY CAUSING HYPOTHYROIDISM

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Abstract
The thyroid glands of 2 hypothyroid goitrous siblings aged 13 and 14 and of a 21-yr-old hypothyroid goitrous female were examined. In all 3 patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12.9-20.0 .mu.g/dl) and low serum T4 [thyroxine] concentration suggested the presence of increased serum levels of iodoalbumin. Serum T3 [triiodothyronine] levels were normal or low normal (80-220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin [Tg] was undetectable in 1 patient, low normal in another and in the normal range for the 3rd one. Except for the patient with undetectable Tg, the 2 other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3 + T4 and MIT + DIT [monoiodotyrosine and diiodotyrosine, respectively]. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had a pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg-like proteins (RIA [radioimmunoassay]) in the thyroid soluble protein extract was only 16-122 .mu.g/g (normal: 50-70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18-20S) thyroglobulin. Only 1 peak (3.6-4.1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively larger amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. A defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA could finally result in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.