Congenital Goitrous Hypothyroidism Research Articles

Lack of thyroid peroxidase activity as the cause of congenital goitrous hypothyroidism.

Studies have been performed on a 52-yr-old female who presented with a goiter, mental deficiency, normal hearing, a serum T4 = 1.0 μg per 100 ml, F T4 = 0.4 ng per 100 ml, total T3 40 ng per 100 ml, BEI = 1.6 μg per 100 ml, BII 0.4 μg per 100 ml and a serum TSH of 82 μU/ml. The sella turcica was enlarged. The thyroid of the patient had a normal concentration mechanism for iodide; the peak uptake of 131I occurred at 4 hr (17%) and declined to 6.0% in 24 hr. Thiocyanate discharged 68% of the accumulated iodide in 1 hr and 84% in 3 hr. A tissue specific lack of peroxidase activity was found as assessed by the complete failure of thyroid tissue, in vitro, to peroxidize guaiacol, iodinate bovine serum albumin or to oxidize thiocyanate. The addition of hydrogen peroxide (10−4m) or hematin (10−4m) failed to stimulate peroxidase activity. Catalase activity was not excessive. Thyroglobulin was present and could be iodinated in the presence of H2O2 and horseradish peroxidase. Salivary peroxidase activity was presen...

Peroxidase defect in congenital goiter with complete organification block.

A 14-yr-old girl with congenital goitrous hypothyroidism is presented. Thyroidal iodide was released by perchlorate, indicating a complete iodide organification block. Serum total thyroxine was 0.6 μg/100 ml. After iv administration of 131I, thyroid uptake of 42% was reached at 30 min. Subsequently the thyroidal 131I content fell with a half time of 0.76 day. Thyroid clearance was 811 ml/min and chromatographs of serum and urine samples indicated the presence of only free iodide. The thyroid tissue obtained at thyroidectomy established a slice/medium [131I] ratio of 37, which was abolished by KC1O4 but not by methimazole. Enzymatic studies performed on the tissue demonstrated very low peroxidase activity (3% of normal values), according to results in the tyrosine iodinase, triiodide, and guaiacol assays. Preincubation of the enzyme with hematin did not increase activity. Neither digitonin nor deoxycholate + trypsin + acetone produced soluble enzyme. Catalase activity was normal and cytochrome c reductase,...

Studies on mono- and diiodohistidine. II. Congenital goitrous hypothyroidism with thyroglobulin defect and iodohistidine-rich iodoalbumin production.

Butanol-insoluble iodinated compounds in the urine of patients with congenital goiters have been generally regarded as iodopeptides. Monoiodohistidine (MIH) and diiodohistidine (DIH) were identified from the urine of four patients with congenital goitrous hypothyroidism. From radioiodine studies, 40-70% of the urinary radioactivity was in the iodide-free fraction from which about 40% was identified as MIH and DIH by crystallizations to a constant specific activity. Iodotyrosines were simultaneously identified in the urine. However the presence of an iodotyrosine-deiodinase activity was demonstrated in the two removed goiters with a normal K(m) for MIT. In vivo iodotyrosine deiodination was normal for hypothyroid subjects. No thyroglobulin was identified in the thyroids from these patients. The major iodoprotein was iodoalbumin which, after in vivo labeling, contained 84-89% of the total soluble protein radioactivity. The thyroxine content of the goiter iodoalbumins and other iodoproteins was extremely low. Iodohistidines were identified in comparable proportions in the iodoalbumin and in the other iodoproteins isolated from each goiter. The average iodohistidine content of these proteins as crystallizable MIH and DIH was in the individual cases 15 and 4% of the in vivo incorporated radioiodine. DIH was identified in all iodoprotein fractions. The mean DIH/MIH ratios from the individual cases were 1.16 and 0.35. The corresponding DIT/MIT ratios were 3.19 and 1.45, respectively. The major consequence of this thyroglobulin defect is the iodination of inappropriate proteins (mainly albumin) resulting in low yields of thyroxine and high yields of iodohistidines. Iodohistidines from the goiter iodoproteins were not deiodinated and, at least for MIH, were quantitatively excreted in the urine of these patients. From the MIH iodoalbumin content and the MIH urinary excretion, goiter iodoalbumin turnover estimates were made and, although elevated, could not maintain a normal thyroxine secretion. The urinary excretion of iodohistidines easily demonstrated by column chromatography is offered as a test for detecting this variety of congenital goiter.

Congenital goiter with impaired thyroglobulin synthesis.

Two cases of congenital hypothyroidism with goiter are reported. The first was that of a 15-yr-old girl with typical goitrous cretinism, the second of a 12-yr-old boy with congenital goitrous hypothyroidism of a milder degree. Extensive clinical and biochemical studies revealed a complete absence of thyroglobulin. The only thyroidal iodoprotein detected, whether by stable or radioactive iodine analysis, had the characteristics of iodinated serum albumin. This iodoprotein was also detected after in vivo 125I labeling in the serum of one case in which it was sought. Non-iodinated thyroglobulin immunoreactive material of small molecular weight was present in very small concentrations in both glands, representing probably normal or abnormal precursors of thyroglobulin. Other inherited biochemical defects in hormonogenesis could not be detected in these cases. It is concluded that absence of thyroglobulin synthesis may represent one of the causes of congenital hypothyroidism with goiter (thyroid dyshormonogene...

12. Studies on thyroid proteins in congenital goiter

Congenital goitrous hypothyroidism may be caused by a metabolic bloc in the synthesis of the thyroid hourmones or by an abnormal synthesis of iodinated proteins in the thyroid. Previously we have utilized labeling in vitro with 3H-leucine and Na125I in the study of the normal synthesis of 17-19 S thyroglobulin in the human fetal thyroid gland (Olin, Vecchio, Ekholm, and Almqvist: Endocrinology, 86: 1041, 1970). This system has been applied to 2-10 mg specimens from congenital goiters obtained by percutaneous biopsy.

Peptide-linked iodotyrosines and iodothyronines in the blood of a patient with congenital goiter.

A case of congenital goitrous hypothyroidism is reported. Studies were made to determine whether a metabolic defect was present. Intravenously administered I131-labeled diiodotyrosine and thyroxine were metabolized normally. Electrophoresis of plasma proteins after in vitro addition of I131-labeled thyroxine demonstrated normal amounts of thyroxine-binding protein. I131 was rapidly concentrated by the gland, and administration of potassium thiocyanate did not cause the release of trapped iodide. Endogenously labeled material in the serum was 60–65 per cent insoluble in butanol. The soluble fraction proved to be thyroxine and triiodothyronine. Starch-block electrophoresis and ultracentrifugation identified the butanol-insoluble portion as an abnormal iodinated protein having the mobility of albumin. This protein was not precipitated by equine anti-human serum albumin. After enzymatic hydrolysis of plasma, mono- and diiodotyrosine, thyroxine, and triiodothyronine were identified on paper chromatograms. This...