Effect of Methimazole and Dexamethasone on Leucocyte Glucocorticoid Receptor, Plasma ACTH, and Cortisol Levels in Graves' Disease

Thirty-two cases of newly diagnosed Graves' disease with hyperthyroidism were recruited in this study on the changes of leucocyte glucocorticoid receptor (GCR), plasma ACTH, and cortisol levels befor and after treatment with methinazole (tapazole) alone (n=16) and methimazole combined with Dexamethasone (Dex, TD group, n=16). Twenty normals served as the control. Methimazole treatment was initiated with a dosage of 40 mg/d, tapered to 20 mg/d after two weeks and maintained until complete remission in both groups. Meanwhile, Dex 6 mg/d was added to the TD group along with methimazole from the commencement of therapy. The dosage of Dex was reduced to 4. 5 mg/d on the 5th day and to 2. 25 mg/d two weeks after treatment, and continued until remission. It was found that there was remarkable decrease in leucocyte GCR levels with a moderate elevation of plasma ACTH and a slight decline of plasma cortisol in untreated Graves' disease, suggestive of a compensation of the pituitary-adrenal axis function in hyperthyroidism. The levels of GCR, ACTH and cortisol returned to normal after complete remission by methimazole in the methimazole alone group. In the TD group, however, all GCR, ACTH and cortisol levels were significantly decreased after Dex therapy, implying down regulation of GCR by exogenous Dex and suppresion of the pituitary-adrenal axis. Thus the dosage of glucocorticoid should be appropriately adjusted to avoid adrenal insufficiency, especially in case of stress, due to the suppresion of pituitary adrenal function.