糖皮质激素冲击治疗甲状腺相关性眼病对肾上腺皮质功能的影响

Effect of high-dose glucocorticoid on adrenal cortex in treatment of thyroid associated ophthalmopathy

目的评价大剂量糖皮质激素冲击治疗对甲状腺相关性眼病(TAO)患者肾上腺皮质功能的影响。方法选取48例活动性中、重度TAO患者,采用分层随机方法分入间歇治疗组(24例)和维持治疗组(24例)。两组患者均予甲泼尼龙500mg/d静脉滴注,连续3d为1个疗程,每个疗程间间隔4周,共冲击治疗6个疗程。维持治疗组患者于间歇期口服泼尼松10mg/d,并于4周内停药。分别于治疗前及治疗结束后第4、24周测定治疗有效者的临床活动性评分(CAS评分)、美国甲状腺协会Graves眼病的分级(NOSPECS)、眼部情况(突眼度、眼外肌厚度及复视情况)及眼内压,并测定血清皮质醇、促肾上腺皮质激素(ACTH)和24h尿皮质醇水平以评估其肾上腺皮质功能。结果两组间治疗前甲状腺功能及相关抗体水平的差异均无统计学意义(P值均>0.05)。治疗结束后第4周,间歇治疗组的治疗有效率为83.3%(20/24),维持治疗组为87.5%(21/24),差异无统计学意义(P>0.05);治疗结束后第24周,间歇治疗组的复发率为20.0%(4/20),维持治疗组为19.0%(4/21),差异无统计学意义(P>0.05)。治疗结束后第4、24周,两组治疗有效者的CAS评分、NOSPECS分级、突眼度、复视发生率、眼外肌厚度均显著低于同组治疗前(P值均<0.05)。治疗结束后第4周,两组治疗有效者的眼内压均显著低于同组治疗前及治疗结束后第24周(P值均<0.05)。两组治疗有效者治疗前各项肾上腺皮质功能的指标均正常;维持治疗组治疗结束后第4周的血清皮质醇、ACTH及24h尿皮质醇水平均较同组治疗前及治疗结束后第24周显著下降(P值均<0.05)。维持治疗组的不良反应发生率为85.7%(18/21),显著高于间歇治疗组的30.0%(6/20,P<0.05)。结论大剂量甲泼尼龙间歇冲击治疗TAO有效,间歇期口服泼尼松者的疗效无显著改善,且不良反应较大,对肾上腺皮质功能有明显抑制作用。

Objective To evaluate the effect of high-dose glucocorticoid on adrenal cortex in patients with thyroid associated ophthalmopathy （TAO）. Methods A total of 48 patients with active severe TAO were divided into intermittent treatment group （.n = 24） and maintenance treatment group （n = 24） by stratified random method. All patients received intravenous infusion of methylprednisolone 500 mg/d for 3 consecutive days as a course of treatment at intervals of 4 weeks （a total of of six courses）. In the maintenance group, the patients were treated with oral prednisone in the interim period; the initial dose was 10 mg/d and the drug was gradually reduced and stopped within four weeks. The function of thyroid gland and the levels of related antibodies were examined before treatment. Clinical activity score （CAS） and NOSPECS level were evaluated, and the ocular condition, including exophthalmos, the thickness of extraocular muscles, double vision and intraocular pressure was assessed before treatment, 4 and 24 weeks after treatment. At the same time, the levels of serum cortisol, adrenocorticotropic hormone （ACTH） and 24-hour urinary cortisol were detected. Results There were no significant differences in the function of thyroid gland or the levels of related antibodies between two groups （all P〉0.05）. Neither werethe effective rate of treatment （83.3 % in the intermittent treatment group and 87.5 % in the maintenance treatment group） at the end of the treatment and recurrence rate （20.0% in the intermittent treatment group and 19.0% in the maintenance treatment group） 4 to 24 weeks after treatment （P〉0. 05）. （AS score, NOSPECS level, exophthalmos, the thickness of extraocular muscles and intraocular pressure were significantly decreased 4 and 24 weeks after treatment as compared with those before treatment （all P〈0.05）. And intraocular pressure at the end of 24 weeks after treatment was significantly lower than that at 4 weeks after treatment （all P〈0.05）. Adrenocortical function was normal before treatment and 4 weeks afer treatment. In the maintenance treatment group, the levels of serum cortisol, adrenocorticotropic ho~ （ACTH） and 24-hour urinary cortisol were significantly lower than those before treatment and 24 week after treatment （all P〈0.05）. The incidence of adverse reaction in the maintenance treatment group was significantly higher than that in the intermittent treatment group （85.7% vs. 30.0%, P〈0.05）. Conclusions High dose mathylprednisolone intermittent therapy is effective for thyroid associated ophthalmopathy. The clinical outcomes are not significantly improved in the patiens with oral prechisone in the interval, but there are more adverse effects and the adrenal function is significantly inhibited.