库欣综合征患者小剂量与大剂量地塞米松抑制试验之间的关系

目的 探讨库欣综合征患者小剂量地塞米松抑制试验中血清皮质醇水平抑制程度与大剂量地塞米松抑制试验可受抑制(血清皮质醇水平被抑制50%以上)之间的关系,及其对库欣病的诊断价值.方法 回顾性分析广州中山大学附属第二医院1990年1月至2009年1月收治的91例库欣综合征患者,观察过夜小剂量(1 mg)地塞米松抑制试验中血清皮质醇水平被抑制20%、30%、40%和50%以上与过夜大剂量(8 mg)地塞米松抑制试验可受抑制之间的关系,并比较上述各切点对库欣病诊断的敏感性与特异性.结果 在过夜1 mg地塞米松抑制试验中血清皮质醇水平被抑制的程度(较基础08:00血清皮质醇水平下降的百分比)与在过夜8 mg地塞米松抑制试验中血清皮质醇水平被抑制的程度相关(r=0.649,P<0.001);在过夜1 mg地塞米松抑制试验中血清皮质醇水平被抑制20%、30%、40%和50%以上的例数分别为30、22、13和9例.在这些患者中,过夜8 mg地塞米松抑制试验可受抑制的例数分别为23例(76.7%)、20例(90.9%)、12例(92.3%)和9例(100.0%).血清皮质醇水平被1 mg地塞米松抑制20%、30%、40%和50%以上对库欣病诊断的敏感性分别为52.8%、32.7%、22.6%和15.7%,特异性分别为94.7%、94.7%、97.4%和97.4%.结论 对于库欣综合征患者,若血清皮质醇水平可被过夜1 mg地塞米松抑制20%以上者,大多数也可被过夜8 mg地塞米松抑制试验所抑制,并且其大多数为库欣病患者.     

大小剂量地塞米松抑制试验对亚临床库欣综合征的诊断价值

目的探讨大小剂量地塞米松抑制试验(DST)对亚临床库欣综合征的诊断价值。方法选取2007年6月—2013年6月我院及中山大学附属第一医院诊治的肾上腺意外瘤患者80例,对其临床资料进行分析,根据小剂量(2 mg)及大剂量(8 mg)DST结果分组。A组(n=15):2 mg及8 mg DST均不能抑制;B组(n=18):2 mg DST不能抑制,8 mg DST能抑制;C组(n=47):2 mg及8 mg DST均能抑制。对3组患者临床症状、生化指标及激素检测值进行统计分析。结果 A组和B组患者超重、肥胖、高血压、糖耐量异常、血脂异常发生率及腰臀比(WHR)、收缩压、舒张压、空腹血糖(FBG)、餐后2 h血糖(2 h FBG)、TC、TG、LDL-C、0:00及8:00血皮质醇(FC)、24 h尿游离皮质醇(VFC)均高于C组,而血促肾上腺皮质激素(ACTH)低于C组(P0.05)。本研究中亚临床库欣综合征患者共29例,其中15例(51.7%)大小剂量DST结果一致,其余14例(48.3%)大小剂量DST结果不一致。结论亚临床库欣综合征患者中约有半数表现为大小剂量DST结果不一致的现象,约半数表现为大剂量DST不能被抑制,因此小剂量DST对亚临床库欣综合征的诊断价值大。     

库欣综合征筛查中不同剂量过夜地塞米松抑制试验诊断价值的比较

目的评价不同剂量（1 mg和2 mg）过夜地塞米松抑制试验（ODST）在库欣综合征筛查中的诊断价值,探究最佳筛查药物剂量和诊断切点,以提高临床工作中对该疾病的检出率,减少药物对人体可能造成的不良反应。 方法回顾性分析从2000年1月至2017年12月山东大学附属省立医院内分泌代谢病科收治并确诊的96例库欣综合征患者及61例临床怀疑经完善检查排除库欣综合征的患者的临床资料,在相同诊断切点下,比较不同剂量试验后血清皮质醇抑制程度及诊断敏感性、特异性;在相同剂量药物下,比较不同诊断切点在疾病筛查中的敏感性、特异性。 结果在1 mg过夜地塞米松抑制试验中,库欣综合征组皮质醇抑制率为17.9%,非库欣综合征组为78.7%;在2 mg过夜地塞米松抑制试验中,库欣综合征组皮质醇抑制率为24.2%,非库欣综合征组为87.2%。以试验当天8:00血清皮质醇为基础值,以次日8:00血清皮质醇<50 nmol/L（1.8 μg/dl）为库欣综合征诊断切点,1 mg ODST诊断库欣综合征的敏感性、特异性分别为为100%、42.8%;2 mg ODST诊断库欣综合征的敏感性及特异性分别为100%、69.7%;若以次日8:00血清皮质醇<138 nmol/L（5 μg/dl）为库欣综合征诊断切点,1 mg ODST诊断库欣综合征的敏感性、特异性分别为为100%、85.7%,2mg ODST诊断库欣综合征的敏感性、特异性为100%、93.9%。在库欣综合征的筛查中,在相同诊断切点下,2 mg ODST比1 mg ODST诊断结果更可靠;在相同剂量药物下,以次日8:00血清皮质醇<138 nmol/L（5 μg/dl）作为诊断切点,诊断敏感性无明显差别,特异性更高,诊断更准确。 结论综上所述,在库欣综合征筛查过程中,以次日8:00血清皮质醇<138 nmol/L（5 μg/dl）为库欣综合征诊断切点,进行2 mg ODST的诊断准确性明显提高,诊断结果更为可靠,值得在实践中推广应用。     

诊断库欣综合征时多种检查方法的比较

目的评价诊断库欣综合征时多种临床试验方法的敏感性和特异性。方法在173例临床确诊库欣综合征患者中进行血、尿皮质醇测定,血皮质醇昼夜节律观察和地塞米松抑制试验,并与术后病理结果进行比较。结果库欣综合征患者血皮质醇节律消失者为92.9%,其中二点法节律消失率为85.1%(8:00,16:00)及91.8%(8:00,24:00),三点法为94.7%(8:00,16:00,24:00)。尿游离皮质醇(UFC)升高者为94.7%。小剂量地塞米松抑制试验不能抑制者为79.7%(1mg)和84.3%(2mg)。血皮质醇基础值升高者为75.6%。库欣病患者行8mg地塞米松抑制试验,以抑制率50%为标准时,敏感性为50%~70%,特异性高于95%。结论诊断库欣综合征敏感性最强的检测指标为血皮质醇昼夜节律的消失和UFC增高。血皮质醇昼夜节律用三点法评价较二点法敏感性高。8mg地塞米松抑制试验是鉴别库欣病和肾上腺皮质腺瘤最合适的方法。     

联合法与经典法地塞米松抑制试验诊断Cushing综合征价值的比较

目的 评价联合法及经典法小及大剂量地塞米松抑制试验（DST）诊断Cushing综合征的价值。方法 回顾性分析北京协和医院1997-2006年152例经手术病理证实的Cushing综合征病例，将经典法与联合法小及大剂量DST结果与病理诊断结果相比较。结果 过夜小剂量DST、经典小剂量DST和联合法之小剂量DST对Cushing综合征定性诊断的符合率分别为97.5％、96．1％和97．6％。3组之间差异无统计学意义（P=0.86）。经典大剂量、联合法之大剂量DST时Cushing病诊断的符合率分别为80．6％、76.4％，2组之间差异无统计学意义（P=0．73）。经典大剂量、联合法之大剂量DST对肾上腺皮质激素（ACTH）非依赖性Cushing综合征诊断的符合率分别为94．2％和95．5％，2组之间差异无统计学意义（P=0．83）。经典法分别行小及大剂量和联合法小及大剂量DST诊断Cushing病的敏感性分别为81．5％和77．8％，特异性分别为92．5％和95．5％。结论 联合法小及大剂量DST比经典法分别行小及大剂量DST操作简便，节省时间，对照值更加准确，2种方法对诊断的符合率差异没有统计学意义，联合法小及大剂量DST可用于Cushing综合征的定性、定位诊断。     

联合法与经典法地塞米松抑制试验诊断Cushing综合征价值的比较

目的评价联合法及经典法小及大剂量地塞米松抑制试验(DST)诊断Cushing综合征的价值。方法回顾性分析北京协和医院1997—2006年152例经手术病理证实的Cushing综合征病例,将经典法与联合法小及大剂量DST结果与病理诊断结果相比较。结果过夜小剂量DST、经典小剂量DST和联合法之小剂量DST对Cushing综合征定性诊断的符合率分别为97.5%、96.1%和97.6%。3组之间差异无统计学意义(P=0.86)。经典大剂量、联合法之大剂量DST对Cushing病诊断的符合率分别为80.6%、76.4%,2组之间差异无统计学意义(P=0.73)。经典大剂量、联合法之大剂量DST对肾上腺皮质激素(ACTH)非依赖性Cushing综合征诊断的符合率分别为94.2%和95.5%,2组之间差异无统计学意义(P=0.83)。经典法分别行小及大剂量和联合法小及大剂量DST诊断Cushing病的敏感性分别为81.5%和77.8%,特异性分别为92.5%和95.5%。结论联合法小及大剂量DST比经典法分别行小及大剂量DST操作简便,节省时间,对照值更加准确,2种方法对诊断的符合率差异没有统计学意义,联合法小及大剂量DST可用于Cushing综合征的定性、定位诊断。     

大剂量地塞米松抑制试验不可抑制的库欣病患者临床和生化特点分析

目的 分析大剂量地塞米松抑制试验(high-dose dexamethasone suppression test,HDDST)不可抑制的库欣病患者临床和生化特点.方法 回顾性分析1991至2006年我院经手术病理证实为垂体ACTH腺瘤的库欣病患者60例,根据HDDST(2 mg/次,每6 h 1次,连用48 h)结果将患者分为抑制组(抑制≥50%)和不可抑制组,比较两组间临床和生化指标差异.结果 (1)23.3%的患者(14/60)HDDST不可抑制,抑制组和不可抑制组的平均年龄[(33.8±10.4 vs 36.2±11.2)岁]和平均病程[(2.1±1.6 vs 3.9±3.1)年]相近(P＞0.05).(2)临床症状:与抑制组比较,不可抑制组双下肢浮肿(64.3% vs 32.6%)、低血钾(71.4% vs 28.3%)、继发性糖尿病(57.1% vs 26.1%)和皮肤紫纹的发生率(85.7% vs 54.3%)明显增高(均P＜0.05);两组的高血压、中心性肥胖、色素沉着等症状的发生率相仿(均P＞0.05).(3)激素水平:不可抑制组8:00的血ACTH[(31.7±17.8 vs 17.6±11.6)pmol/L]、皮质醇[(1144.3±354.1 vs 696.1±207.9)nmol/L]和24 h尿游离皮质醇[UFC(2760.3±1 851.0 vs 1208.0 ±690.0)nmol/24h]较抑制组明显增高(均P＜0.01);而两组午夜(0:00)血ACTH和皮质醇水平相似(均P＞0.05).(4)生化检查:不可抑制组的血钾更低[(3.2±0.7 vs 3.8±0.6)mmol/L],二氧化碳结合力更高[(29.3±3.6 vs 26.6±3.6)mmol/L](均P＜0.01).结论 HDDST不可抑制的库欣病患者8:00的血ACTH、皮质醇和24 h UFC水平增高更明显,容易出现下肢浮肿、皮肤紫纹、高血糖和低血钾,代谢性碱中毒的程度也更严重.     

去氨加压素兴奋试验在库欣综合征中的诊断价值

研究表明,血管加压素是促肾上腺皮质激素的一种有效促泌剂,去氨加压素作为血管加压素的一种长效类似物,可用于促肾上腺皮质激素依赖性库欣综合征的诊断与鉴别诊断,排除假性库欣综合征与非促肾上腺皮质激素依赖性库欣综合征。此外,去氨加压素兴奋试验还可作为库欣病患者（术前去氨加压素兴奋试验为阳性反应者）术后随访的一个生化指标。     

库欣综合征的识别

库欣综合征是引起继发高血压的原因之一,临床较为少见,心内科就诊的患者容易误诊或者漏诊。本文以一例年轻患者的诊断为例,简介了高血压查因和库欣综合征的诊治流程,供心内科医生参考。     

Performance of the 4-mg intravenous dexamethasone suppression test in differentiating Cushing disease from pseudo-Cushing syndrome

ContextDiscriminating Cushing disease (CD) from pseudo-Cushing syndrome (PCS) is a challenging task that may be overcome with the 4-mg intravenous (IV) dexamethasone suppression test (DST).ObjectiveAssess the performance of the 4-mg IV DST in the differential diagnosis between CD and PCS in well-characterized patients.DesignRetrospective comparative study of subjects seen in a tertiary care unit (November 2008 to July 2011).MethodsThirty-six patients with PCS and 32 patients with CD underwent 4-mg IV dexamethasone infusions from 11 am to 3 pm. Areas Under ROC Curves (AUCs) were estimated and compared for ACTH and cortisol measured at 4 pm the same day (day 1) and 8 am the next day (day 2). The ROC curve of the marker with the highest AUC was used to determine the threshold with the highest specificity for 100% sensitivity.ResultsThe AUC of ACTH at 8 am on day 2 was estimated at 98.4% (95% CI: [92.1–100]), which is significantly greater than that of ACTH at 4 pm on day 1 (P = 0.04) and that of cortisol at 8 am on day 2 (P = 0.05). For ACTH at 8 am on day 2, the threshold with the highest specificity for 100% sensitivity was estimated at 14.8 ng/L. At this threshold, the sensitivity was estimated at 100% [89–100] and the specificity at 83.3% [67–94].ConclusionThe 4-mg IV DST is an easy and accurate tool in distinguishing CD from PCS. It deserves thus a better place in establishing the diagnosis of CD.     

An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause--60 with Cushing's disease, 7 with the ectopic adrenocorticotrophic hormone syndrome, and 9 with adrenal tumors--suppression of plasma cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17-hydroxycorticosteroids or plasma cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.     

Relationship of nonalcoholic hepatic steatosis to overnight low-dose dexamethasone suppression test in obese individuals

OBJECTIVES: To examine the association between nonalcoholic hepatic steatosis (HS) and the activity of the hypothalamo-pituitary-adrenal (HPA) axis, as evaluated by a low-dose dexamethasone suppression test, in obese subjects. DESIGN AND PATIENTS: In a cross-sectional study, we examined 54 obese, otherwise healthy, individuals with a negligible or zero daily alcohol consumption. MEASUREMENTS: HS (by ultrasonography), glucose tolerance status (by oral glucose load), insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. RESULTS: Subjects with nonalcoholic HS (n = 39) had markedly less suppressed circulating cortisol levels than those without HS (n = 15) (21.9 +/- 2.6 vs. 11.0 +/- 1.4 nmol/l, P < 0.001). In addition, subjects with nonalcoholic HS had significantly higher values of HOMA-insulin resistance score and circulating liver enzymes than their counterparts without HS. Age, body mass index (BMI), waist/hip ratio, plasma glucose concentration (both at fasting and after glucose load), lipids and blood pressure values did not differ significantly between the groups. Females were more represented among those without HS. The marked differences in postdex suppression cortisol levels that were observed between the groups were little affected by adjustment for sex, age, BMI, waist/hip ratio, HOMA-insulin resistance score, plasma lipids and liver enzyme levels. Similarly, in a logistic regression analysis, cortisol levels significantly predicted the presence of nonalcoholic HS (P = 0.032), independently of potential confounders. CONCLUSIONS: These results suggest that nonalcoholic hepatic steatosis is closely correlated with a subtle, chronic activation of the HPA axis in obese, otherwise healthy, individuals.     

Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome.

OBJECTIVE: To develop criteria for interpreting the high-dose dexamethasone suppression test using urine free cortisol as an end point for the differential diagnosis of the Cushing syndrome. DESIGN: Retrospective review. SETTING: Inpatient research ward. PATIENTS: Patients (118) with surgically confirmed causes of the Cushing syndrome: 94 with pituitary disease, 14 with primary adrenal disease, and 10 with ectopic adrenocorticotropic hormone (ACTH) secretion. MAIN OUTCOME MEASURES: The sensitivity, specificity, and diagnostic accuracy were determined for the high-dose dexamethasone suppression test using urine free cortisol and using 17-hydroxysteroid excretion. For each analysis, patients with pituitary disease were considered to be "diseased" and patients with nonpituitary disease were considered to be "non-diseased". The level of suppression that gave 100% specificity was determined for each steroid. RESULTS: The accuracy of urine free cortisol when used as an end point in the high-dose dexamethasone suppression test was equivalent to that of 17-hydroxysteroid excretion. At all levels of sensitivity and specificity, however, the degree of suppression of urine free cortisol used for the diagnosis of pituitary disease was greater than that of 17-hydroxysteroid excretion. The likelihood ratios for pituitary disease based on urine free cortisol suppression of greater than 50%, of greater than 80%, and of greater than 90% were 4.2, 10.1, and "infinite," respectively. Suppression of urine free cortisol greater than 90% or suppression of 17-hydroxysteroid excretion greater than 64% was associated with 100% specificity. When these criteria were combined, the percentage of correct predictions (102 of 118 [86%; 95% CI, 78% to 92%]) was higher than that obtained using either steroid alone (89 of 118 [75%; CI, 65% to 83%]) (P = 0.009) and higher than that obtained using the traditional criterion of 50% suppression for 17-hydroxysteroid excretion (95 of 118 [80%; CI, 71% to 87%]) (P = 0.016). CONCLUSIONS: In the high-dose dexamethasone suppression test, the degree of suppression of urine free cortisol used for the diagnosis of pituitary disease is greater than that traditionally used for 17-hydroxysteroid excretion. The diagnostic performance of the test is improved by measuring both urine free cortisol and 17-hydroxysteroid excretion and by requiring greater suppression of both steroids.     

Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing's syndrome

CONTEXT: The low-dose dexamethasone suppression test (LDDST) is widely used in confirming a diagnosis of Cushing's syndrome. CRH administration at the end of an LDDST has been reported to improve the diagnostic accuracy of this test. OBJECTIVE: Our objective was to assess whether CRH administration after a standard LDDST (LDDST-CRH test) improves diagnostic accuracy in Cushing's syndrome. DESIGN, SETTING, AND PARTICIPANTS: Thirty-six individuals with a clinical suspicion of Cushing's syndrome each completed a standard LDDST and an LDDST-CRH test at Hammersmith Hospitals NHS Trust, London. The LDDST involved administration of 0.5 mg oral dexamethasone given 6-hourly for 48 h. Serum cortisol was measured 6 h after the last dose of dexamethasone, with a value of 50 nmol/liter or below excluding Cushing's syndrome. Immediately after this, the LDDST-CRH test commenced with administration of a ninth dose of 0.5 mg dexamethasone. Exactly 2 h later, 100 mug human-sequence CRH was administered. Serum cortisol was measured 15 min after the CRH injection, with a value of less than 38 nmol/liter also excluding Cushing's syndrome. MAIN OUTCOME MEASURE: Diagnosis or exclusion of Cushing's syndrome was the main outcome measure. RESULTS: Twelve subjects were diagnosed with Cushing's syndrome (eight Cushing's disease and four primary adrenal). The sensitivity of the LDDST in diagnosing Cushing's syndrome was 100%, with a specificity of 88%. In contrast, although the sensitivity of the LDDST-CRH test was also 100%, specificity was reduced at 67%. These results give a positive predictive value of 80% for the LDDST and 60% for the LDDST-CRH test. CONCLUSION: This small study suggests that the addition of CRH to the LDDST does not improve the diagnostic accuracy of the standard LDDST in Cushing's syndrome.     

Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing's syndrome

Cushing's syndrome requires a screening test of high sensitivity, followed by biochemical evaluation of the source of the tumor when the cause is ACTH dependent. The high-dose dexamethasone suppression test is still in common use as an aid in differential diagnosis, although its value has been queried. We have routinely used the low-dose dexamethasone suppression test for many years in the diagnosis of Cushing's syndrome but noticed that patients with pituitary-dependent Cushing's syndrome or Cushing's disease, usually showed some degree of suppression of their serum cortisol, compared to those with the ectopic ACTH syndrome. We therefore analyzed retrospectively the serum cortisol responses during the low-dose dexamethasone suppression test and the high-dose dexamethasone suppression test in 245 patients with ACTH-dependent Cushing's syndrome and compared the diagnostic utility of each test either alone or in combination with a standard test using CRH. Evaluation of the serum cortisol response at 24 and 48 h during the low-dose dexamethasone suppression test correctly identified 98% of patients with ACTH-dependent Cushing's syndrome and distinguished between pituitary and ectopic causes with a sensitivity of 82% and a specificity of 79%. In the same patients, the serum cortisol response to the high-dose dexamethasone suppression test had a slightly higher sensitivity (91%) and specificity (80%). However, the combined criteria of a more than 30% suppression of serum cortisol during the low-dose dexamethasone suppression test and/or a more than 20% increase in the CRH test had a significantly higher sensitivity (97%) and specificity (94%) than either the high-dose dexamethasone or the CRH tests alone in the differential diagnosis of ACTH-dependent Cushing's syndrome. It produced equivalent information to that when high-dose and CRH test results were combined. We therefore conclude that in our patient series, the serum cortisol response during the low-dose dexamethasone suppression test is highly sensitive in diagnosing Cushing's syndrome and, combined with the results of the serum cortisol response to the CRH test, offered a safe and cost-effective test in the differential diagnosis of ACTH-dependent Cushing's syndrome. There does not appear to be any necessity for retaining the high-dose dexamethasone suppression test in this diagnostic work-up.