Kotaro Nagai

Anti-bovine thyrotropin autoantibodies in patients with Hashimoto’s thyroiditis, subacute thyroiditis, and systemic lupus erythematosus

We report four cases found to have anti-bovine thyrotropin (bTSH) antibodies, two with Hashimoto’s thyroiditis and the other two, each with subacute thyroiditis and systemic lupus erythematosus (SLE). The unusually high negative titers of anti-TSH receptor antibodies (Case no. 1, −43.1%; Case no. 2, −34.9%; Case no. 3, −55.2%; Case no. 4, −59.9%) led to the incidental finding of the presence of anti-bovine (bTSH) antibodies in each patient. Case no. 1 was diagnosed to have Hashimoto’s thyroiditis and was treated with L-thyroxine (L-T4). With the treatment, serum free T4 (FT4)normalized with a decline in the serum TSH concentration. The other patient diagnosed to have Hashimoto’s thyroiditis (Case no. 2) remained euthyroid even without supplemental thyroid hormone therapy and the serum concentrations of FT4 and TSH stayed within the normal range. The third is a case of subacute thyroiditis (Case no. 3) with a typical clinical course of the disease. She had the anti-bTSH antibodies on her first outpatient visit. Serial examination of her sera disclosed the antibody titers to be on the same range over the 28 months after the onset of the symptoms. The fourth is a patient with SLE who had been treated with steroid (alternative day therapy of 40 mg/day prednisolone). Titers of the anti-bTSH antibodies spontaneously declined to the negative level 5 months later. None of the four cases had antibodies against human TSH α-subunit of bovine LH and α-subunit of bovine FSH. Except for the SLE patient whose anti-bTSH antibodies disappeared spontaneously, the rest of the three patients persistently showed the antibodies suggesting a continuous anti-genic stimulation by bTSH or bTSH-like molecule.

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.

A case of rheumatoid arthritis associated with silent thyroiditis

A 41-year-old female with rheumatoid arthritis had nontender enlarged thyroid gland. Thyroid function tests revealed increased concentrations of serum free T3 (FT3, 10.8 pmol/L) and free T4 (FT4, 31.1 pmol/L) with suppressed concentration of thyrotropin (TSH, lower than 0.1 mU/L) and low 24-hour thyroidal radioactive iodine uptake (1.6%). Serum thyrotropin receptor antibody (TRAb) was negative (0%) and she had positive anti-thyroglobulin and anti-microsomal antibodies. A diagnosis of silent thyroiditis was made based on laboratory findings. Serum concentrations of FT3 and FT4 normalized one month later without treatment. The causal relationship between the two diseases is discussed.

Two cases of Graves’ disease with antithyroid hormone antibodies: Implication on the role of thyroglobulin as an antigen

We have experienced two cases of Graves’ disease with antithyroid hormone autoantibodies (Case 1: anti-T4; Case 2: anti-T3) who finally underwent subtotal thyroidectomy after antithyroid drug treatment. Using serial sera obtained before and after operation, the correlation between titers of antithyroglobulin (anti-Tg) and anti-T4 or anti-T3 autoantibodies was examined in each case. There was a significant positive correlation between titers of anti-T4 (Case 1, r = 0.90, p < 0.05), or anti-T3 (Case 2, r = 0.64, p < 0.01) and anti-Tg antibodies. Using the homogenate of the thyroid tissue, it was found that the sole iodoprotein in the thyroid gland in each patient was 660 KDa Tg. In addition, Tg purified from the thyroid gland from Case 2 showed different immunological activity with normal Tg in two out of four murine monoclonal anti-Tg antibodies tested. On the other hand, Tg from Case 1 had identical immunological activity with normal Tg in every four monoclonal antibodies. These results are consistent with the view that the antigen responsible for the development of antithyroid hormone autoantibodies is Tg, at least in our two cases. The reason for the persistence of anti-T3 autoantibodies in Case 2, despite the subtotal thyroidectomy, could be due to some unidentified structural abnormalities of Tg which was detected only by the monoclonal anti-Tg antibodies.

A case of diabetes mellitus associated with anti-insulin autoantibodies without previous insulin injection

A case of diabetes mellitus who had high levels of fasting immunoreactive insulin (IRI) and low levels of immunoreactive C-peptide (CPR) is reported. Examination of her serum disclosed the presence of IgG class k + λ type anti-insulin autoantibodies. She has never been treated with insulin, nor had drugs which have been reported to be responsible for inducing insulin autoimmune syndrome. Despite the presence of autoantibodies against insulin, she has never experienced hypoglycemia. Significance of the production of autoantibodies against insulin and physicochemical parameters of anti-insulin antibodies in her serum are discussed.

Insulin Binding to Erythrocytes in Chronic Glucocorticoid Deficiency

The effect of chronic glucocorticoid deficiency on insulin binding to erythrocyte was evaluated in 2 cases of ACTH deficiency, 2 of Sheehans syndrome and a case of Addisons disease before and after the replacement therapy with cortisone acetate. 75 gram oral glucose tolerance test (OGTT) was also performed. Mean fasting plasma glucose (FPG) and insulin (FIRI) before (70.2 mg/dl, 3.6 microU/ml) and after (75.4 mg/dl, 7.8 microU/ml) therapy were significantly lower than those in normal control (97.0 mg/dl, 12.0 microU/ml). The ratio of FIRI/FPG before and after treatment were also significantly lower than that in control subjects. Glucose areas during OGTT before and after treatment were not different from that in control subjects. However, insulin area before treatment was significantly lower than that in control group. There were significant increases in FIRI/FPG and insulin area, but not in FPG and glucose area before and after treatment. Insulin binding to erythrocytes before treatment (11.9 +/- 1.1%, mean +/- SD) was greater than that in normal subjects (7.7 +/- 1.9%, n = 19, p less than 0.05). It was significantly decreased and normalized to 7.8 +/- 2.0% by the treatment. Analysis of binding parameters revealed the increases in receptor concentration at high affinity site (R1) and in average affinity at empty site by average affinity profile (Ke) before treatment in comparison with control subjects. There was no significant difference in binding parameters after treatment and in control group. High R1 or low R2 observed before treatment was significantly decreased or increased after treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of primary hepatocellular carcinoma associated with hyperthyroxine-binding-globulinemia].

概 要: 高thyroxine binding globulin(TBG)血 症 を伴 つた原発 性 肝細 胞癌(肝 癌)の1例 で,血 清 中TBG,α-fetoprotein(AFP)値 が,肝 癌 の進 行 と共 に平行 して上昇,両 者 が解 離 し た死 亡 直前の値 を除 くと正 の相 関(r=0.846,p<0 .05)が 認 め られた.血 清thyroxine(T4), triiodothyronine(T3)値 はTBGと 平行 して増加 したが, free T4 (F-T4), free T3(F-T3) 値 は正常範 囲y-か 正 常 下限 で あつ た.ま た,本 例 のTBGのT3 T4に 対 す る結合 定数 は,低 値 で あ つた.以 上 か ら,本 例 の肝 癌組 織 よ りAFPと 同様,T3,T4結 合 能 の低下 した異 常 なTBGも 産 生 され た可能性 が示 唆 され た.ま た,末 期 には,血 中immunoreactive insulin(IRI)低 値 を 伴 つ た低血 糖 発 作が 頻発 し,insulin-1ike activity(ILA)産 生肝 癌 の可能性 も残 され た. 〔日内会誌 75:1644~1649,1986〕