Noriko Kojima

Serum concentrations of osteocalcin in patients with hyperthyroidism, hypothyroidism and subacute thyroiditis

Serum concentration of osteocalcin (OC) was measured in sera from untreated patients with Graves’ disease, hypothyroidism due to Hashimoto’s thyroiditis, and subacute thyroiditis. Serum concentration of OC in Graves’ disease and hypothyroidism were 14.1+5.6 μ/L and 3.8±2.7 μg/L, respectively which were significantly different from that of healthy subjects (Graves’ disease, p<0.001, hypothyroidism, p<0.01). Serum concentration of OC in patients with subacute thyroiditis was 8.0+3.5 μ/L which was not statistically different from age-matched normal controls. Serial measurement of serum OC for 24 mo in 15 patients with Graves’ disease after initiation of antithyroid drugs disclosed that the decline of serum OC was obtained only 24 mo after antithyroid drug therapy. On the other hand, in hypothyroid patients, increased serum OC was observed after 1-2 months treatment of L-T4. Correlation coefficients between serum concentrations of OC and T3, T4, FT3 or FT4 in all the patients with thyroid disorders were 0.66, 0.51, 0.50 and 0.54, respectively, which were statistically significant (all, p<0.001). These results suggest that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism. In hyperthyroid patients, despite of normalization of FT4 concentration in relatively short period (within 3-4 mo), it took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion. In contrast to thyrotoxic patients, rapid increase in serum OC after initiation of supplemental L-T4 treatment in hypothyroidism was observed, suggesting a direct effect of thyroid hormone on the osteoblasts in patients with hypothyroidism.

Effect of 8-anilino-1-naphthalene sulfonic acid (ANS) on the interaction between thyroid hormone and anti-thyroid hormone antibodies

Effect of 8-anilino-1-naphthalene sulfonic acid (ANS) on the interaction between thyroid hormone and anti-thyroid hormone antibodies was examined. Addition of 5.1 x 10(6) or 6.3 x 10(6) molar excess of ANS, respectively, enhanced the binding of 125I-T3 or 125I-T4 to their respective autoantibodies. However, further increase in ANS concentration resulted in a decrease in binding. These results suggest that the optimum concentration of ANS for the detection of anti-thyroid hormone antibodies is 5 approximately 6 x 10(6) molar excess of ANS to 125I-T3 or 125I-T4. On the other hand, addition of 10(4) molar excess of ANS concentration decreased the binding of 125I-insulin to anti-insulin antibodies. It was therefore suggested that the effect of ANS could be a nonspecific one and likely due to its negative charge.

Autoimmune Recognition of Thyroglobulin and Thyroid Hormones in Rabbits

Two rabbits (RG-1, RG-2) were immunized with rabbit thyroglobulin (RTg) purified from thyroid glands of four other normal rabbits of the same strain, and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. Production of anti-RTg as well as anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed in both rabbits. Physicochemical parameters of anti-RTg antibodies with RTg, T4, and T3 were calculated in two selected antisera (70-day and 253-day) of each of the rabbits, using a Scatchard plot. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of T3 and T4 in immune sera than in preimmune serum. Examination of pathology of thyroid glands and kidneys in both rabbits was negative for the lesions of autoimmune thyroiditis and immune nephritis. These results indicate that anti-Tg as well as anti-thyroid hormone autoantibodies can be raised without thyroid pathology in rabbit by immunization with autologous Tg.

Concentrations of free thyroxine, total thyroxine, and total triiodothyronine in rabbits immunized with human thyroglobulin.

Levels of serum free thyroxine, total triiodothyronine and total thyroxine were measured in two rabbits (TG-1, TG-2) which had been immunized with human thyroglobulin and produced both anti-thyroglobulin and anti-thyroid hormone antibodies. Despite the presence of both anti-triiodothyronine and -thyroxine antibodies, levels of serum free thyroxine in serial sera obtained from a rabbit (TG-1) stayed within normal range up to 249 days after the first immunization, whereas in the other rabbit (TG-2), serum free thyroxine concentrations of serial sera declined after three immunizations and stayed at lower levels than normal range up to 249 days. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of triiodothyronine and thyroxine in immune sera than preimmune sera. From these results, it is concluded that the presence of anti-thyroid hormone antibodies per se can reduce serum level of free thyroxine in rabbits.