Abstract：
BACKGROUND: Cushing\'s syndrome due to ectopic ACTH secretion is a rare clinical condition resulting from a dysregulated ACTH secretion by neuroendocrine tumors, which can have various localizations and different histological differentiations. The overall incidence of endogenous Cushing\'s syndrome is 0.7-2.4 per million people per year. Children account for just 10% of all new cases that are reported each year.
METHODS: When the patient first presented clinically, she was a 17-year-old girl who displayed symptoms of schizophrenia (delirium, psychotic episodes, and hallucinations). Blood tests showed diabetes mellitus and hypokalemia. She was also affected by high blood pressure and osteoporosis complicated by D9-D10 and L1-L5 vertebral collapses. For these reasons, she was treated with aripiprazole, insulin glargine, potassium chloride, spironolactone, enalapril, and calcium carbonate. After two months of treatment, she was referred to the pediatrician endocrinologist, who diagnosed hypercortisolism after prescribing hormone tests (Table 1). After receiving her diagnosis, she began taking 1000 mg of metyrapone and had a whole-body CT scan, which revealed bilateral adrenal hyperplasia. The results of the 68Ga-PET/DOTATOC and 18FDG-PET scans were negative. The clinical course was intermittent in the months that followed, with hypercortisolism and eucortisolism alternating. After one year of treatment, a 68Ga-PET/DOTATOC showed a nodule in the thymic lodge (Fig. 1). The patient underwent a thymectomy. Unfortunately, after surgery, she continued to have high levels of cortisol, for which she continued metyrapone 750 mg/die. 68Ga-PET/DOTATOC repeated three months after surgery showed again an uptake corresponding to the thymic lodge (Fig. 2). In order to remove the neuroendocrine lesion, she had a new surgery, which resulting a finally resolutive. ACTH levels were monitored before, during, and post-surgery (Table 2). The laboratory provided the ACTH results very quickly and thoracic surgeons waited for hormonal results before concluding the procedure. The adopted strategy permitted us to monitor the outcome of the surgery.
CONCLUSIONS: The heterogeneity of ectopic Cushing\'s syndrome makes diagnosis difficult. Treatment of ectopic Cushing\'s syndrome requires close clinical, biochemical, and instrumental observation. Metyrapone is a drug able to control hypercortisolism in a lasting way with a good level of safety. 68Ga-PET/DOTATOC proves to be a tracer with good sensitivity and specificity for the identification of ACTH-secreting neuroendocrine lesions. The short half-life of ACTH is found to be a strategy to monitor the complete surgical resection of the neuroendocrine lesion. A multidisciplinary approach improves therapeutic success and reduces the risk of recurrence.
METHODS: When the patient first presented clinically, she was a 17-year-old girl who displayed symptoms of schizophrenia (delirium, psychotic episodes, and hallucinations). Blood tests showed diabetes mellitus and hypokalemia. She was also affected by high blood pressure and osteoporosis complicated by D9-D10 and L1-L5 vertebral collapses. For these reasons, she was treated with aripiprazole, insulin glargine, potassium chloride, spironolactone, enalapril, and calcium carbonate. After two months of treatment, she was referred to the pediatrician endocrinologist, who diagnosed hypercortisolism after prescribing hormone tests (Table 1). After receiving her diagnosis, she began taking 1000 mg of metyrapone and had a whole-body CT scan, which revealed bilateral adrenal hyperplasia. The results of the 68Ga-PET/DOTATOC and 18FDG-PET scans were negative. The clinical course was intermittent in the months that followed, with hypercortisolism and eucortisolism alternating. After one year of treatment, a 68Ga-PET/DOTATOC showed a nodule in the thymic lodge (Fig. 1). The patient underwent a thymectomy. Unfortunately, after surgery, she continued to have high levels of cortisol, for which she continued metyrapone 750 mg/die. 68Ga-PET/DOTATOC repeated three months after surgery showed again an uptake corresponding to the thymic lodge (Fig. 2). In order to remove the neuroendocrine lesion, she had a new surgery, which resulting a finally resolutive. ACTH levels were monitored before, during, and post-surgery (Table 2). The laboratory provided the ACTH results very quickly and thoracic surgeons waited for hormonal results before concluding the procedure. The adopted strategy permitted us to monitor the outcome of the surgery.
CONCLUSIONS: The heterogeneity of ectopic Cushing\'s syndrome makes diagnosis difficult. Treatment of ectopic Cushing\'s syndrome requires close clinical, biochemical, and instrumental observation. Metyrapone is a drug able to control hypercortisolism in a lasting way with a good level of safety. 68Ga-PET/DOTATOC proves to be a tracer with good sensitivity and specificity for the identification of ACTH-secreting neuroendocrine lesions. The short half-life of ACTH is found to be a strategy to monitor the complete surgical resection of the neuroendocrine lesion. A multidisciplinary approach improves therapeutic success and reduces the risk of recurrence.
摘要：
背景：由异位ACTH分泌引起的库欣综合征是一种罕见的临床病症，是由神经内分泌肿瘤引起的ACTH分泌失调引起的，可以有不同的定位和不同的组织学分化。内源性库欣综合征的总体发病率为每年每百万人中0.7-2.4人。儿童仅占每年报告的所有新病例的10％。
方法：当患者首次出现临床时，她是一个17岁的女孩，表现出精神分裂症的症状(谵妄，精神病发作,和幻觉）。血液检查显示糖尿病和低钾血症。她还受到高血压和骨质疏松症的影响，并伴有D9-D10和L1-L5椎骨塌陷。由于这些原因,她接受了阿立哌唑治疗,甘精胰岛素,氯化钾,螺内酯,依那普利,和碳酸钙。经过两个月的治疗,她被介绍给儿科医生内分泌学家，在处方激素测试后诊断为皮质醇增多症（表1）。在收到她的诊断后,她开始服用1000毫克的甲吡酮，并进行了全身CT扫描，提示双侧肾上腺增生。68Ga-PET/DOTATOC和18FDG-PET扫描结果为阴性。在随后的几个月中，临床过程是间歇性的，皮质醇增多症和全心激素增多症交替出现。经过一年的治疗,a68Ga-PET/DOTATOC显示胸腺小屋有结节（图。1).患者接受了胸腺切除术。不幸的是,手术后,她的皮质醇水平仍然很高,为此，她继续使用Metyrapone750mg/die。手术后三个月重复的68Ga-PET/DOTATOC再次显示出与胸腺小屋相对应的摄取（图。2).为了切除神经内分泌病变,她做了新手术,最终产生了决定性的结果。之前监测过ACTH水平,during,和手术后（表2）。实验室很快提供了ACTH结果，胸外科医生在结束手术之前等待激素结果。所采用的策略使我们能够监测手术的结果。
结论：异位库欣综合征的异质性使诊断变得困难。异位库欣综合征的治疗需要密切的临床，生物化学，和仪器观察。Metyrapone是一种能够以持久的方式控制皮质醇增多症的药物，具有良好的安全性。68Ga-PET/DOTATOC被证明是用于鉴定分泌ACTH的神经内分泌病变的具有良好敏感性和特异性的示踪剂。发现ACTH的短半衰期是监测神经内分泌病变的完全手术切除的策略。多学科方法可提高治疗成功率并降低复发风险。
方法：当患者首次出现临床时，她是一个17岁的女孩，表现出精神分裂症的症状(谵妄，精神病发作,和幻觉）。血液检查显示糖尿病和低钾血症。她还受到高血压和骨质疏松症的影响，并伴有D9-D10和L1-L5椎骨塌陷。由于这些原因,她接受了阿立哌唑治疗,甘精胰岛素,氯化钾,螺内酯,依那普利,和碳酸钙。经过两个月的治疗,她被介绍给儿科医生内分泌学家，在处方激素测试后诊断为皮质醇增多症（表1）。在收到她的诊断后,她开始服用1000毫克的甲吡酮，并进行了全身CT扫描，提示双侧肾上腺增生。68Ga-PET/DOTATOC和18FDG-PET扫描结果为阴性。在随后的几个月中，临床过程是间歇性的，皮质醇增多症和全心激素增多症交替出现。经过一年的治疗,a68Ga-PET/DOTATOC显示胸腺小屋有结节（图。1).患者接受了胸腺切除术。不幸的是,手术后,她的皮质醇水平仍然很高,为此，她继续使用Metyrapone750mg/die。手术后三个月重复的68Ga-PET/DOTATOC再次显示出与胸腺小屋相对应的摄取（图。2).为了切除神经内分泌病变,她做了新手术,最终产生了决定性的结果。之前监测过ACTH水平,during,和手术后（表2）。实验室很快提供了ACTH结果，胸外科医生在结束手术之前等待激素结果。所采用的策略使我们能够监测手术的结果。
结论：异位库欣综合征的异质性使诊断变得困难。异位库欣综合征的治疗需要密切的临床，生物化学，和仪器观察。Metyrapone是一种能够以持久的方式控制皮质醇增多症的药物，具有良好的安全性。68Ga-PET/DOTATOC被证明是用于鉴定分泌ACTH的神经内分泌病变的具有良好敏感性和特异性的示踪剂。发现ACTH的短半衰期是监测神经内分泌病变的完全手术切除的策略。多学科方法可提高治疗成功率并降低复发风险。
