Junko Tachi

Digoxin-like immunoreactivity in Chinese medicine

Immunoreactive digoxin-like activity was observed in Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Chan-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with similar chemical structure as digoxin. One tablet of KYUSHIN had digoxinlike immunoreactivity equivalent to 1.9, 1.5, and 72μg of digoxin measured by three different commercial kits. These different equivalences may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 μg/L in 0.5 day. Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Chan-su component.

Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease.

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in‐vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves’ disease was evaluated by this ‘natural in‐vivo human assay’. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin‐binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL‐5 cells (thyroid‐stimulating antibody, TSAb). Further, the binding‐stimulation index (B‐S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5–10 days after birth) born to 20 mothers with Graves’ disease who had positive TBII and/or TSAb (FT4I: r= 0.825 for TBII, r= 0.908 for TSAb, r= 0.944 for the B‐S index, P > 0.001; FT3I: r = 0.622 for TBII, P > 0.01, r= 0.812 for TSAb, r= 0.791 for the B‐S index, P > 0.001; n= 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves’ disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B‐S index and FT4I found in neonates was applied to values in adult patients with Graves’ disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B‐S index. FT4I and the ratio of FT4I to the B‐S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B‐S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B‐S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves’ disease (r=−0.288, P >0.05). The results suggest that in‐vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves’ disease may be regulated not only by circulating thyroid‐stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.

Postpartum Onset Of Graves’ Disease

Pregnancy markedly influences the clinical course of autoimmune thyroid diseases (1, 2). Graves’ disease is aggravated in early pregnancy but ameliorated in the later half of pregnancy (3). Hashimoto’s disease is also ameliorated during pregnancy and slightly increased levels of serum TSH are often returned into normal range in association with the progress of pregnancy (4). Contrary to amelioration of disease during pregnancy, both Graves’ disease and Hashimoto’s disease are aggravated after delivery and various types of thyroid dysfunction, as shown in Figure 1, are frequently observed (3~5).