Kedem Eynat, Shahar Eduardo, Hassoun Gamal, Pollack Shimon
Institute of Clinical Immunology, Allergy and AIDS, Rambam Health Care Campus, Haifa, Israel.
J Asthma. 2010 Sep;47(7):830-1. doi: 10.3109/02770903.2010.485666.
Iatrogenic Cushing's syndrome (CS) is caused by exposure to glucocorticoids and may be promoted by interaction with additional drugs. It is well known in asthmatic human immunodeficiency virus (HIV)-infected patients treated with inhaled fluticasone with ritonavir-containing antiretroviral regimen (cART).
The authors present an asthmatic HIV-infected Ethiopian woman, treated with fluticasone/salmeterol, commencing cART with tenofovir, emtricitabine, and lopinavir/ritonavir. During 7 months she gained 9 kg and hyperpigmentation, mild edema, marked abdominal striae, and increase in blood pressure were noted. Plasma am and urine free cortisol levels confirmed CS diagnosis and fluticasone was discontinued. Complete resolution of CS occurred within 2 months. However, frequent asthma symptoms required resumption of inhaled corticosteroid (ICS) treatment, and budesonide/formeterol was prescribed. Soon reemergence of symptomatic CS was noted. Ritonavir dose was halved, but CS symptoms continued to develop. Budesonide was stopped and montelukast initiated. Resolution of cushingoid symptoms was observed within weeks.
Corticosteroids are metabolized by cytochrome P450 3A4 (CYP3A4). Fluticasone has the longest glucocorticoid receptor-binding half-life and is 300 times more lipophilic than budesonide. Inhaled fluticasone possesses a high suppression rate of hypothalamic-pituitary-adrenal axis. Ritonavir, a potent CYP3A4 inhibitor, may inhibit corticosteroid degradation and increase its accumulation. Inhaled budesonide is less likely to cause adrenal suppression. Diagnosing Cushing's syndrome presents a clinical challenge due to similarities with clinical manifestations and side effects related to cART. In patients treated with inhaled or intranasal corticosteroids together with cART there may be a higher incidence of iatrogenic CS. CS should be looked for, and management considered carefully.
医源性库欣综合征（CS）由接触糖皮质激素引起，可能因与其他药物相互作用而加重。在接受吸入性氟替卡松联合含利托那韦的抗逆转录病毒疗法（cART）治疗的哮喘合并人类免疫缺陷病毒（HIV）感染患者中，这一情况已为人熟知。
作者介绍了一名患有哮喘的HIV感染埃塞俄比亚女性，她接受氟替卡松/沙美特罗治疗，并开始使用替诺福韦、恩曲他滨和洛匹那韦/利托那韦进行cART治疗。在7个月内，她体重增加了9千克，出现了色素沉着、轻度水肿、明显的腹部条纹和血压升高。血浆上午和尿游离皮质醇水平确诊为CS，遂停用氟替卡松。2个月内CS完全缓解。然而，频繁的哮喘症状需要恢复吸入性糖皮质激素（ICS）治疗，于是开具了布地奈德/福莫特罗。很快，有症状的CS再次出现。利托那韦剂量减半，但CS症状仍持续发展。停用布地奈德并开始使用孟鲁司特。数周内观察到库欣样症状缓解。
皮质类固醇由细胞色素P450 3A4（CYP3A4）代谢。氟替卡松具有最长的糖皮质激素受体结合半衰期，亲脂性比布地奈德高300倍。吸入性氟替卡松对下丘脑 - 垂体 - 肾上腺轴具有较高的抑制率。利托那韦是一种强效CYP3A4抑制剂，可能抑制皮质类固醇降解并增加其蓄积。吸入性布地奈德致肾上腺抑制的可能性较小。由于与cART相关的临床表现和副作用相似，诊断库欣综合征面临临床挑战。在接受吸入或鼻内皮质类固醇联合cART治疗的患者中，医源性CS的发生率可能更高。应留意CS并谨慎考虑治疗方案。
