Biochemical Studies on the Iodine Organification Defect of Pendred's Syndrome

Abstract

Biochemical studies were performed on the thyroid of a typical case of Pendred's syndrome who underwent total thyroidectomy. The patient, a euthyroid 14 year old female, presented congenital nerve deafness, goitre and impairment of thyroidal iodine organification. Thyroid peroxidase (TPO) activity was quantitatively normal. Using crude preparations, enzyme activity ranged from 176\p=n-\366 nmoles of I \ m= -\ \ x = r e q -\ incorporated (inc.) to tyrosine/g of tissue. Normal values are 220\p=n-\410 nmoles I\m=-\inc./g. Digitonin pseudosolubilized TPO, assayed by the tyrosine-iodinase method, showed 44.9 nmoles I\m=-\ inc./mg of protein for the Pendred's tissue, and 44.5 nmoles I\m=-\ inc./mg for the control glands. Soluble TPO was utilized for enzyme-kinetic studies. The Km for H2O2, obtained in the triiodide assay with iodide as hydrogen donor, was in the same order of magnitude for both Pendred's and control thyroids, being 3 \ m=x\ 10\m=-\4 m and 3.5 \ m=x\10\m=-\4 m, respectively. In the guaiacol assay, the Pendred's Km value of 4 \ m=x\10\m=-\4 m was also normal for H2O2. Pre-incubation of enzyme preparations with 5 \m=x\10\m=-\5m haematin did not stimulate TPO activity. Thyroidal NADPH-cytochrome c reductase and monoamine oxidase activities were normal. A low concentration, 37 mg/g, of a qualitatively normal thyroglobulin was found in Pendred's goitre. The iodine content of thyroglobulin was 0.19 %.

Defective Organification of Iodide Causing Hereditary Goitrous Hypothyroidism

“…Other studies performed in thyroid tissues from patients with congenital goiter and defective TPO have indicated that the Tg obtained from these tissues can be normally iodinated and has a normal coupling reaction in vitro when incubated with hog TPO. In tissues with defective TPO, as expected, little MIT or DIT is formed, with only traces of T3 or T4 (66). It is conceivable that some Tg might be iodinated, some with T3 and T4 formation due to some TPO activity.…”

“…In retrospect, however, we may assume that the majority of cases had a quantitative type of TPO defect. This conclusion is reached through comparison with other documented instances of quantitative TPO deficiency (57,59,64,66,70,75,78). Strong points favoring a clinical diagnosis of a quantitative defect are large goiters, a complete discharge of iodide following perchlorate, more than one sibling affected in the family, consanguinity, and severe hypothyroidism.…”

“…In one study, the solubilized TPO was able to oxidize iodide but had 60-80% less activity in iodinating thyroglobulin (36). Others have found normal TPO activity in tissue obtained from patients with Pendred's syndrome (37,38). The controversy may be solved by molecular biological methods exploring the TPO mRNA and the translated protein in thyroid tissues from patients with Pendred's syndrome.…”

A Case of Pendred’s Syndrome Presenting with Amenorrhea

“…Quan titative and qualitative studies done on thyroid peroxi dase in patients with Pendred's syndrome have been nor mal [5], Mason et al [6] have demonstrated abnormalities of the messenger ribonucleic acid encoding the 3-prime region of thyroglobulin. The exact nature of the biochemi cal defect in Pendred's syndrome remains unknown.…”

Goitre and Deaf-Mutism

“…Morgans and Trotter in 1958 demonstrated a presumed specific enzymatic defect as the cause of goitre in this condition [17]. The thyroid defect has been shown to be a partial defect in iodine organification leading to the under production of thyroxine [18]. This triggers the secretion of thyroid stimulating hormone (TSH) which stimulates thyroid gland hyperplasia to compensate for the defect by maintaining the minimal level of thyroid hormones production to keep the patient euthyroid.…”