van den Berg S A A, van 't Veer N E, Emmen J M A, van Beek R H T
Laboratory for Clinical Chemistry and Haematology, Amphia Hospital, BredaThe Netherlands.
Laboratory for Clinical Chemistry, Erasmus MC, RotterdamThe Netherlands.
Endocrinol Diabetes Metab Case Rep. 2017 Apr 6;2017. doi: 10.1530/EDM-16-0158. eCollection 2017.
We present a case of iatrogenic Cushing's syndrome, induced by treatment with fluticasone furoate (1-2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i.e. striae of the upper legs, full moon face, increased body and facial hair) within weeks after starting fluticasone furoate therapy, which was exacerbated after increasing the dose to 2 dd because of complaints of unresolved rhinitis. Biochemical analysis fitted iatrogenic Cushing's syndrome, with a repeatedly low cortisol (<0.03 µM, ref 0.14-0.60 µM) and low ACTH (9 pg/mL, ref 9-52 pg/mL) without signs of adrenal insufficiency. No other biochemical abnormalities that could point to adrenal or pituitary dysfunction were detected; electrolytes, thyroid and gonadal function, and IGF-1 were within the normal range. Pharmacogenetic analysis revealed that the pediatric patient carried the and genotype (associated with a partial and complete loss of enzyme activity, respectively) which is associated with the development of iatrogenic Cushing's syndrome in patients treated for HIV due to the strong inhibition of CYP3 enzymes by Ritonavir. Upon discontinuation of fluticasone treatment, the pediatric patient improved both clinically and biochemically with normalisation of cortisol and ACTH within a couple of weeks.
Fluticasone therapy may induce iatrogenic Cushing's syndrome in a patient treated with anti-retroviral therapy.Pharmacogenetic analysis, in particular CYP3A genotyping, provides useful information in patients treated for HIV with respect to possible future steroid treatment.Fluticasone furoate is not detected in the Siemens Immulite cortisol binding assay.
我们报告了一例医源性库欣综合征病例，该病例由糠酸氟替卡松（每日1 - 2次，每侧鼻孔27.5μg）治疗一名先天性HIV患儿引起。本病例报告中的患儿是一名非洲裔年轻女孩，接受洛匹那韦/利托那韦（每日1次，320/80mg）、拉米夫定（每日1次，160mg）和阿巴卡韦（每日1次，320mg）联合治疗先天性HIV。我们的患儿在开始糠酸氟替卡松治疗数周内出现典型的库欣样特征（即大腿出现条纹、满月脸、身体和面部毛发增多），因鼻炎症状未缓解将剂量增加至每日2次后症状加重。生化分析符合医源性库欣综合征，皮质醇反复降低（<0.03μM，参考值0.14 - 0.60μM）且促肾上腺皮质激素降低（9pg/mL，参考值9 - 52pg/mL），无肾上腺功能不全迹象。未检测到其他可能提示肾上腺或垂体功能障碍的生化异常；电解质、甲状腺和性腺功能以及胰岛素样生长因子-1均在正常范围内。药物遗传学分析显示该患儿携带 和 基因型（分别与酶活性部分和完全丧失相关），由于利托那韦对CYP3酶的强烈抑制作用，这与接受HIV治疗的患者发生医源性库欣综合征有关。停用氟替卡松治疗后，患儿临床和生化指标均有改善，皮质醇和促肾上腺皮质激素在几周内恢复正常。
氟替卡松治疗可能在接受抗逆转录病毒治疗的患者中诱发医源性库欣综合征。药物遗传学分析，特别是CYP3A基因分型，对于接受HIV治疗的患者未来可能的类固醇治疗提供有用信息。西门子免疫化学发光法皮质醇结合试验未检测到糠酸氟替卡松。
