Mizuo Azukizawa

Familial Isolated Thyrotropin Deficiency with Cretinism

Abstract Two sisters with nongoitrous cretinism, offspring of a consanguineous marriage, were found to have isolated thyrotropin (TSH) deficiency. Growth hormone, ACTH and gonadotropin secretion we...

DIFFERENTIATION OF THYROTOXICOSIS INDUCED BY THYROID DESTRUCTION FROM GRAVES' DISEASE

Thyroid function was tested in untreated patients with Graves disease or thyrotoxic subacute thyroiditis, and in patients with autoimmune thyroiditis who showed postpartum or spontaneous transient thyrotoxicosis. The serum triiodothyronine/thyroxine ratio (T3/T4) was greater than 20 ng/microgram in Graves disease but less than 20 in all patients with subacute thyroiditis and 9 of 11 patients with autoimmune thyroiditis. Thus, like radioactive iodine uptake, the serum T3/T4 ratio is useful for differentiating destruction-induced thyrotoxicosis from the stimulation-induced hyperthyroidism of Graves disease.

Longitudinal study or serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy.

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3′‐triiodothyronine (T3), free T3, 3,3′,5′‐triiodothyronine (reverse T3, rT3), thyroxine‐binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age‐matched, non‐pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.

Kinetic aspects of the antigen-antibody reaction in various radioimmunoassays: Effect of delayed addition of labeled or unlabeled antigens on sensitivity of assay

The kinetics of the antigen-antibody reaction were examined systematically in four kinds of double-antibody radioimmunoassay (RIA). In all the RIAs, the dose-response curves obtained on delayed addition by 24 to 48 h of labeled antigens (curves B), were shifted downwards and to the left of those obtained on simultaneous addition of the reagents (curves A), resulting in improved sensitivity of the assay. On the contrary, the dose-response curves obtained on delayed addition of unlabeled antigens (curves C), were shifted upwards and to the right of curves A, resulting in reduced sensitivity. In human thyrotropin (hTSH) RIA, curves B and C approached curves A very little, even after 168 h of incubation. A similar phenomenon was observed with anti-hTSH antisera from five different sources at two incubation temperatures, and the dilution curves of 125I-labeled hTSH and unlabeled hTSH appeared to be parallel. Therefore, the phenomenon observed with hTSH RIA could not be attributed to the assay conditions or to peculiar properties of the reagents used. In insulin RIA, the reversibilities of the shifts of curves B and C were slight but comparable to those observed in hTSH RIA. In 1-3,5,3-triiodothyronine RIA, curves B and C gradually approached curves A on prolonged incubation and curves B became nearly identical with curves A after 98 h of incubation. On the other hand, in alpha-fetoprotein (AFP) RIA, curves B and C did not approach curves A, even on prolonged incubation for up to 288 h. The equilibrium affinity constants of the antibodies were of the same order of magnitude, thus it is unlikely that differences in the constants can account for the differences in the reversibility of these RIAs. In APF RIA, a significant amount of the antigen-antibody complex was precipitated without second antibody after centrifugation at 3000 X g. These findings suggest that the extent of dissociation of the immune complexes depends on their size, which in turn is related to the molecular weight of the antigen.

Pathogenesis of Hyperthyroidism

I. TSH secretion in patients with Graves disease 1. In hyperthyroid patients, serum TSH levels determined by radioimmunoassay were undetectable (<1.0 /2U/m1). 2. Three euthyroid patients with Graves disease were treated with 1-methyl-2mercaptoimidazole followed by thyroxine. Reciprocal changes in TSH and thyroxine levels were observed, but LATS did not change. II. LATS in Graves disease 1. Concentration and identification of LATS : LATS cantaining IgG which was separated from serum by DEAE-Sephadex column chromatography was passed through a CM-C column, and LATS fractions with high specific activity were obtained. The