甲巯咪唑和地塞米松对Graves甲亢患者白细胞糖皮质激素受体、血浆ACTH及皮质醇的影响

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

研究了３２例Ｇｒａｖｅｓ甲亢（甲亢）患者单用甲巯咪唑及联用地塞米松（Ｄｅｘ）治疗前后白细胞糖皮质激素受体（ＧＣＲ），血浆皮质醇（ＰＴＣ）和血浆ＡＣＴＨ的变化。开始甲巯咪唑４０ｍｇ／ｄ，两周后减至２０ｍｇ／ｄ，直至完全缓解。联用Ｄｅｘ组除甲巯咪唑外，开始加Ｄｅｘ６ｍｇ／ｄ，第５日减至４．５ｍｇ／ｄ，两周后减至２．２５ｍｇ／ｄ，直至完全缀解。结果发现，未治甲亢患者的白细胞ＧＣＲ水平显著降低，ＰＴＣ略降、ＡＣＴＨ轻度升高，提示甲亢时垂体－肾上腺轴机能处于代偿状态。单用甲巯咪唑组治疗后病情缓解，ＧＣＲ、ＡＣＴＨ及ＰＴＣ恢复正常。联用甲巯咪唑及Ｄｅｘ组治疗后，ＧＣＲ、ＡＣＴＨ及ＰＴＣ均显著降低，揭示ＧＣＲ呈下降调节，同时垂体－肾上腺轴受外源性Ｄｅｘ抑制。因此，甲亢患者使用糖皮质类固醇治疗时应注意调整剂量，以避免由于垂体－肾上腺轴受抑制在应激时发生肾上腺皮质功能不全。

Thirty-two cases of newly diagnosedGraves’disease with hyperthyroidism were recruited inthis study on the changes of leucocyte glucocorticoidreceptor(GCR),plasma ACTH,and cortisol levelshbrand after treatment with methinazole(tapazole)alone (n=16)and methimazole combined with Dexam-ethasone(bex,TD group,n=16).Twenty normalsserved as the control.Methimazole treatment was initiated with a dosage of 40 mg/d,tapered to 20 mg/d after twoweeks and maintained until complete remission in bothgroups. Meanwhile, Dex 6 mg/d was added to the TDgroup along with methimazole from the commence-ment of therapy. The dosage of bex was reduced to4.5mg/d on the 5th day and to 2.25 mg/d two weeksafter treatment, and continued until remission.It wasfound that there was remarkable decrease in leucocyteGCR levels with a moderate elevation of plasmaACTH and a slight decline of plasma cortisol in un-treated Graves’disease,suggestive of a compensationof the pituitary-adrenal axis function in hyperthy-roidism. The levels of GCR,ACTH and cortisol re-turned to normal after complete ren1ission by methima-zole in the methimazole alone group. In the TD group,however.all GcR .ACTH and cortisol levels weresignificantly decreased after Dex therapy implyingdown regulation of GCR by exogenous Dex and sup-presion of the pituitary-adrenal axis. Thus the dosageof glucocorticoid should be appropriately adjusted toavoid adrenal insufficiency,especiall y in case ofstress,due to the suppresion of pituitary adrenal func-tion.