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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 effects of high-dose glucocorticoid therapy on adrenocortical function in patients with thyroid-associated ophthalmopathy (TAO). Methods Forty-eight patients with active and moderate active TAO were enrolled and divided into intermittent treatment group (24 cases) and maintenance therapy group (24 cases) by stratified randomized method. Two groups of patients were given methylprednisolone 500mg / d intravenous infusion, continuous 3d for a course of treatment, each treatment interval of 4 weeks, a total of 6 courses of impact treatment. Patients in the maintenance treatment group were given oral prednisone 10 mg / d during the intermittent period and discontinued within 4 weeks. The clinical activity score (CAS score), the American Thyroid Association Graves ophthalmopathy classification (NOSPECS), the ocular condition (exophthalmos, extraocular muscle thickness And diplopia) and intraocular pressure, and serum cortisol, adrenocorticotrophic hormone (ACTH) and urinary cortisol levels of 24h to assess their adrenocortical function. Results There was no significant difference in thyroid function and antibody level between the two groups before treatment (P> 0.05). At 4 weeks after the end of treatment, the effective rate was 83.3% (20/24) in the intermittent treatment group and 87.5% (21/24) in the maintenance treatment group, with no significant difference (P> 0.05) At 24 weeks, the recurrence rate was 20.0% (4/20) in the intermittent treatment group and 19.0% (4/21) in the maintenance treatment group, with no significant difference (P> 0.05). CAS scores, NOSPECS grade, exophthalmos, incidence of diplopia and extraocular muscle thickness were significantly lower in both groups than those in the same group before treatment (P <0.05) at the 4th and 24th week after treatment. At 4 weeks after the end of treatment, the intraocular pressure of the two groups were significantly lower than before treatment and 24 weeks after the end of treatment (P <0.05). The indexes of each adrenocortical function in the two groups were all normal before treatment. The levels of serum cortisol, ACTH and 24h urinary cortisol in the fourth week after treatment in the maintenance treatment group were significantly higher than those before treatment and 24th after the treatment Week decreased significantly (P <0.05). The incidence of adverse reactions in maintenance therapy group was 85.7% (18/21), significantly higher than that in intermittent treatment group (30.0%, 6/20, P <0.05). Conclusion The high dose of methylprednisolone is effective in treating TAO intermittently, while the effect of intermittent oral prednisone is not significantly improved, and the adverse reaction is large, and the effect on adrenocortical function is obviously inhibited.