Batista Dalia L, Riar Jehan, Keil Meg, Stratakis Constantine A
Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, USA.
Pediatrics. 2007 Sep;120(3):e575-86. doi: 10.1542/peds.2006-2402. Epub 2007 Aug 13.
Endogenous Cushing syndrome in children is a rare disorder that is most frequently caused by pituitary or adrenocortical tumors. Diagnostic criteria have generally been derived from studies of adult patients despite significant differences in both the physiology of the hypothalamic-pituitary-adrenal axis and the epidemiology of Cushing syndrome in childhood. The purpose of this study was to identify the tests that most reliably and efficiently diagnose pituitary or adrenal tumors in a large cohort of pediatric patients with Cushing syndrome.
A retrospective review of clinical data of children who were referred to a tertiary care center for evaluation for Cushing syndrome during the years 1997 to 2005 was conducted. A total of 125 consecutive children were studied retrospectively; 105 were found to have Cushing syndrome, which was confirmed histologically; and 20 children who did not have Cushing syndrome or any other endocrinopathy served as the control group. The following tests were performed in all children: midnight and morning cortisol, corticotropin hormone, urinary free cortisol and 17-hydroxycorticosteroid levels, ovine corticotropin-releasing hormone stimulation test, and overnight high-dosage dexamethasone suppression test. Imaging of the pituitary and adrenal glands was also obtained. The main outcome measure was the sensitivity of these parameters for the diagnosis and differential diagnosis of Cushing syndrome at 100% specificity.
A midnight cortisol value of > or = 4.4 microg/dL confirmed the diagnosis of Cushing syndrome in almost all children, with a sensitivity of 99% and a specificity of 100%. Suppression of morning cortisol levels > 20% in response to an overnight, high-dosage dexamethasone test excluded all patients with adrenal tumors and identified almost all patients with pituitary tumors (sensitivity: 97.5%; specificity: 100%).
Our study suggests that among children who were referred for the evaluation of possible Cushing syndrome, a single cortisol value at midnight followed by overnight high-dosage dexamethasone test led to rapid and accurate confirmation and diagnostic differentiation, respectively, of hypercortisolemia caused by pituitary and adrenal tumors.
儿童内源性库欣综合征是一种罕见疾病，最常见的病因是垂体或肾上腺皮质肿瘤。尽管儿童下丘脑 - 垂体 - 肾上腺轴的生理学以及库欣综合征的流行病学存在显著差异，但诊断标准通常源自对成年患者的研究。本研究的目的是确定在一大群患有库欣综合征的儿科患者中，最可靠且高效地诊断垂体或肾上腺肿瘤的检测方法。
对1997年至2005年期间转诊至三级医疗中心评估库欣综合征的儿童临床资料进行回顾性研究。共对125名连续儿童进行了回顾性研究；其中105名被发现患有库欣综合征，经组织学证实；20名未患库欣综合征或任何其他内分泌病的儿童作为对照组。对所有儿童进行了以下检测：午夜和清晨皮质醇、促肾上腺皮质激素、尿游离皮质醇和17 - 羟皮质类固醇水平、羊促肾上腺皮质激素释放激素刺激试验以及过夜高剂量地塞米松抑制试验。还对垂体和肾上腺进行了成像检查。主要观察指标是这些参数在100%特异性时对库欣综合征诊断和鉴别诊断的敏感性。
午夜皮质醇值≥4.4μg/dL几乎可确诊所有儿童的库欣综合征，敏感性为99%，特异性为100%。过夜高剂量地塞米松试验后清晨皮质醇水平抑制>20%可排除所有肾上腺肿瘤患者，并识别出几乎所有垂体肿瘤患者（敏感性：97.5%；特异性：100%）。
我们的研究表明，在因可能患有库欣综合征而转诊的儿童中，单次午夜皮质醇值检测随后进行过夜高剂量地塞米松试验，分别可快速、准确地确诊由垂体和肾上腺肿瘤引起的高皮质醇血症，并进行诊断鉴别。
