过夜小剂量地塞米松抑制试验对库欣综合征诊断价值的再探讨

目的重新探讨过夜小剂量地塞米松抑制试验对库欣综合征的诊断价值。方法回顾性分析我院1990年1月到2005年7月收治的52例库欣综合征患者和153例经住院检查排除库欣综合征的肥胖症和高血压病患者，比较过夜小剂量（1mg）地塞米松抑制试验的不同血清皮质醇切点对库欣综合征诊断的敏感性和特异性。结果在过夜1mg地塞米松抑制试验中，以试验当日晨8：00血清皮质醇为基础值，次日8：00血清皮质醇为基础值的50％以及次日晨8：00血清皮质醇275、200、138和50nmol／L为切点，诊断库欣综合征的敏感性分别为92．3％、92．3％、92．3％、92．3％和100．0％，特异性分别为90．8％、98．7％、96．1％、91．5％和78．4％。结论在过夜1mg地塞米松抑制试验中，以次日晨8：00血清皮质醇50nmol／L为切点具有较高的敏感性，可作为库欣综合征的第一线筛选试验。     

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。     

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。     

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55例临床分析

目的分析库欣综合征患者的病因分类,各种主要临床表现的出现频率以及实验室检查特点,并对各种诊断方法的效率进行评价。方法收集2003～2008年在我院住院经临床和病理确诊为库欣综合征患者的病例资料,对它们进行回顾性分析。结果在本组病例中,库欣病最多见,肾上腺皮质腺瘤次之。临床表现方面,向心性肥胖和高血压出现的频率最高,均在70％以上。血糖异常和血脂异常的发生率分别为51．43％和70．59％,其中糖尿病的比例高达37．14％。四成以上的患者存在低血钾,肾上腺皮质腺癌患者100％有低血钾,且是重度低血钾。在库欣综合征诊断试验中,敏感性从高到低依次为不被小剂量地塞米松抑制,血皮质醇昼夜节律消失,24小时尿游离皮质醇增高,清晨血皮质醇增高。在库欣综合征患者的鉴别诊断中,80％以上的库欣病患者能被大剂量地塞米松抑制,而几乎94％的肾上腺皮质腺瘤患者不能被大剂量地塞米松抑制。有关影像学检查,垂体MRI可以检测出90％以上的库欣病患者存在垂体腺瘤,而肾上腺CT几乎100％可以发现出肾上腺肿瘤。结论本研究中库欣病和肾上腺皮质腺瘤仍然是最常见的病因,但后者的的比例相对较高。而在临床特点方面,高血压和糖尿病的发生率较高。对于库欣综合征的诊断和鉴别诊断,目前没有一种检查方法具有100％的敏感性,我们应对各种结果作出综合判断。     

双侧岩下窦静脉采血诊断ACTH依赖性库欣综合征的价值

目的 评估双侧岩下窦静脉采血(BIPSS)测定ACTH、垂体MRI动态增强和大剂量地塞米松抑制试验在ACTH依赖性库欣综合征鉴别诊断中的价值.方法 纳入BIPSS并经病理明确诊断的ACTH 依赖性库欣综合征患者87例,行BIPSS、大剂量地塞米松抑制试验和垂体影像学评估.结果 78例病理明确诊断为垂体ACTH瘤,9例为胸腺类癌所致异位ACTH综合征.大剂量地塞米松抑制试验、垂体MRI动态增强和BIPSS诊断敏感性分别为82.1％、79.5％和92.3％,特异性分别为100％、44.4％和100％,诊断准确率分别为83.9％、77.0％和93.1％.库欣病患者BIPSS分侧定位符合率为83.9％,而垂体MRI分侧定位符合率为64.5％.结论 ACTH依赖性库欣综合征中,BIPSS比大剂量地塞米松抑制试验、垂体MRI 动态增强诊断符合率更高.与垂体MRI检查相比,BIPSS分侧定位更为可信.     

肾上腺占位合并垂体病变的库欣综合征九例临床分析并文献复习

目的探讨垂体及。肾上腺均有病变的库欣综合征患者的病因诊断方法。方法回顾性分析9例垂体及肾上腺均病变的患者,行大小剂量地塞米松抑制试验,查血促。肾上腺皮质激素（ACTH）水平,并行鞍区MRI及肾上腺CT。结果（1）血ACTH值在4例库欣病患者中3例高于正常上限,1例正常。5例非ACTH依赖性库欣综合征患者ACTH均〈20ng／L。（2）大剂量地塞米松抑制试验服药第2日24小时尿游离皮质醇在ACTH依赖组均可被抑制到对照值的20％以下,ACTH非依赖组5例患者均未被抑制到对照的50％以下。（3）术后病理支持临床诊断。结论对于兼有肾上腺及垂体两处病变的库欣综合征患者需采用多种方法进行鉴别,最后的判定是术后病理及疗效。     

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.     

肾上腺意外瘤中的亚临床库欣综合征

目的比较肾上腺意外瘤中亚临床库欣综合征与肾上腺无功能瘤的临床及生化特征。方法在18例亚临床库欣综合征与24例肾上腺无功能瘤患者中进行血尿皮质醇、血皮质醇昼夜节律、地塞米松抑制试验,与30例健康对照者比较,并对所有患者进行定期随访。结果(1)亚临床库欣综合征组均匀性肥胖、高血压、糖尿病、高血脂的患病率均高于肾上腺无功能瘤组;(2)亚临床库欣综合征患者8:00血皮质醇、日平均血皮质醇、24:00血皮质醇/8:00血皮醇及24h尿游离皮质醇均高于其余两组,而8:00血ACTH则低,2mg地塞米松抑制试验血尿皮质醇抑制情况也较差;(3)亚临床库欣综合征组中有1例(5.56%)发展为临床显性库欣综合征,其余患者随访中生化指标与入组时测定结果比较无明显变化,2例肾上腺无功能瘤患者随访过程中肿瘤增大。结论部分肾上腺意外瘤患者伴有代谢综合征的表现,尤其在亚临床库欣综合征患者中更为多见;亚临床库欣综合征患者的生化改变较肾上腺无功能瘤患者及对照组明显,后两组生化测值比较无差别;亚临床库欣综合征患者有部分可发展成为临床显性库欣综合征。     

肾上腺意外瘤中亚临床库欣综合征临床研究

目的探讨肾上腺意外瘤中亚临床库欣综合征的临床及危害性。方法2000~2005年对上海交通大学医学院附属瑞金医院的23例亚临床库欣综合征患者进行血糖、血脂、血尿皮质醇、血皮质醇昼夜节律、地塞米松抑制试验检测和观察,并与同期25例肾上腺腺瘤型库欣综合征患者的结果比较。结果(1)亚临床库欣综合征组年龄大于肾上腺腺瘤型库欣综合征组,两组肥胖、高血压、糖代谢异常及高血脂的发生率比较差异无显著性意义,两组体重指数(BMI)、腰臀比、血压、血脂、血糖及胰岛素比较差异均无显著性意义。(2)亚临床库欣综合征组血皮质醇、日平均血皮质醇、夜间皮质醇占清晨分泌量百分比及24h尿游离皮质醇均低于肾上腺腺瘤型库欣综合征组,2mg地塞米松抑制试验后血皮质醇及尿游离皮质醇亦低,两组晨8h血促肾上腺皮质激素(ACTH)比较差异无统计学意义。结论亚临床库欣综合征患者可导致肥胖、高血压、高血脂及糖代谢异常的发生,对患者造成一定的危害,且危害程度与肾上腺腺瘤型库欣综合征相近。     

Cushing综合征的病因诊断与临床特点分析

目的分析Cushing综合征患者的不同病因、临床表现及内分泌实验室检查和影像学检查的特点,评价各种病因鉴别诊断方法的效率。方法对经手术病理确诊为Cushing综合征的42例患者的临床资料和实验室检查、影像学检查等资料进行回顾分析。结果 42例患者的病因以Cushing病占的比例最高,主要临床表现在不同病理类型之间发生率差异无统计学意义。但满月脸、紫纹、皮肤瘀斑在肾上腺瘤中的发生率比其他病理类型为高,64.3%的病人有典型的Cushing外貌,血糖异常、高血压的发生率分别为61.9%、61.9%。Cushing综合征诊断试验的敏感性从高到低依次为不被午夜1mg地塞米松抑制、小剂量地塞米松抑制试验、24h尿游离皮质醇升高、血皮质醇昼夜节律消失、清晨血皮质醇升高。在Cushing综合征的病因鉴别诊断中,93.3%的肾上腺腺瘤病人不被8mg大剂量地塞米松抑制,71.4%的病人被8mg大剂量地塞米松实验抑制。在影像学检查中,肾上腺CT可100%检查出肾上腺腺瘤。结论 Cushing病和肾上腺腺瘤是Cushing综合征最常见的病因。在临床上关注一些有倾向性的表现,并结合ACTH检测、8mg地塞米松抑制试验以及影像学检查,方能对Cushing综合征的病因作出准确的鉴别诊断。     

Screening for Cushing’s syndrome in obese type 2 diabetic patients and the predictive factors on the degree of serum cortisol suppression

The aim of this study was to examine the frequency of Cushing??s syndrome (CS) in obese type 2 diabetic patients devoid of specific clinical symptoms of Cushing??s syndrome. A total of 148 obese (BMI ??30?kg/m² ) type 2 diabetic patients (113 female, 35 male) were included in the study. An overnight 1-mg dexamethasone suppression test (DST) was performed on all patients. Suppression of serum cortisol to <1.8???g/dL after administration of 1?mg dexamethasone was considered normal suppression. Low dose dexamethasone suppression test was performed on the patients who had serum cortisol level over 1.8???g/dL after overnight 1?mg DST. Regression analysis was applied to determine the effective factors on suppression of serum cortisol. Mean age, BMI and HbA1c levels respectively were 50,82?±?8,50?year, 31,78?±?4,66?kg/m², %8,96?±?2,42 in males and 54,15?±?10,348?year, 34,32?±?5.71?kg/m², % 8,18?±?2,06 in females. Serum cortisol level was found 1.64?±?5.62???g/dl after overnight DST. A total of 9 (6.2?%) patients had non-suppressible overnight DST. Only four (2.6 %) of these patients were diagnosed with Cushing Syndrome after low-dose DST. Diagnosis was confirmed pathologically. Etiologic reasons for Cushing??s syndrome were pituitary microadenoma (2 patients) and adrenocortical adenoma (2 patients). Age and duration of diabetes was found to be related to the degree of suppression. Cushing??s syndrome should be investigated in high-risk groups like uncontrolled diabetes, obesity. All the related factors on the degree of suppression must be considered for the final diagnosis.     

Cushing's syndrome in a clinic population with diabetes

Background: A recent report has suggested that occult Cushing’s syndrome (CS) may be present in a significant number of patients with type 2 diabetes mellitus. The aim of this study was to determine whether any patients in our clinic population with diabetes had this condition. Methods: One hundred and seventy‐one consecutive overweight attendees at the diabetic clinic were enrolled in a study to assess the presence of occult CS. The initial screen was with the 1 mg overnight dexamethasone suppression test and follow‐up testing, where indicated was with a 24 h collection for urine‐free cortisol. Results: Thirty‐one of 171 patients had a positive result from the overnight dexamethasone suppression test. Follow‐up testing with 24 h urine‐free cortisol reduced the number of patients with positive results to 3. Two of these were shown to have alcoholic pseudo‐CS. The third patient has had several high urine‐free cortisol results, in the presence of normal scans of pituitary and adrenals. He has no stigmata of CS and is being observed. Conclusion: Based on the results of our study, there would appear to be little value in screening type 2 diabetics for CS, in the absence of clinical suspicion.     

CRF IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING''S SYNDROME: A COMPARISON WITH THE DEXAMETHASONE SUPPRESSION TEST

Accurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin-releasing factor (CRF-41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high-dose dexamethasone suppression test (8 mg/day for 48 h). Of 20 patients with confirmed Cushing's disease (pituitary-dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high-dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF-41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high-dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high-dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.     

Abnormal overnight dexamethasone suppression test in subjects receiving rifampicin therapy.

We have studied the effects of rifampicin on the overnight 1-mg dexamethasone suppression test usually employed to exclude suspected Cushing's syndrome. Previous observations indicate that in humans, rifampicin profoundly attenuates the biological effects of hydrocortisol and prednisolone, probably by increasing the metabolism of these drugs in the liver. The study was carried out in 16 normal volunteers. All subjects had a normal overnight 1-mg dexamethasone suppression test (468 +/- 86 vs. 32 +/- 21 nmol/L; mean +/- SD). In 8 subjects treated with rifampicin (600 mg) for 10 days, the inhibitory effect of dexamethasone on serum cortisol was completely prevented (575 +/- 114 vs. 434 +/- 82). In the remaining 8 rifampicin-treated subjects, the inhibitory effect of 1, 2, or 3 mg dexamethasone on serum cortisol was not observed. When 4 mg dexamethasone were administered, the serum cortisol level was 193 nmol/L, above the expected normal suppression value. The plasma dexamethasone concentration was very low after rifampicin treatment (range, 1.2-4.8 nmol/L). We conclude that when patients are treated with rifampicin, the standard overnight dexamethasone suppression test not only has no diagnostic value, but can be very misleading.     

The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome

Low-dose dexamethasone suppression testing has been recommended for biochemical screening when Cushing's syndrome is suspected. The criterion for normal suppression of cortisol after dexamethasone is controversial. To assess diagnostic utility (sensitivity), we report the results of low-dose dexamethasone suppression testing in 103 patients with spontaneous Cushing's syndrome. There were 80 patients with Cushing's disease (78%), 13 with the ectopic ACTH syndrome (13%), and 10 with cortisol-producing adrenocortical adenomas (10%). Fourteen (18%) of 80 patients with Cushing's disease suppressed serum cortisol to less than 5 micro g/dl (<135 nmol/liter) after the overnight 1-mg test, whereas six patients (8%) actually showed suppression of serum cortisol to less than 2 micro g/dl (<54 nmol/liter). In addition, the 2-d, low-dose dexamethasone suppression test yielded false-negative results in 38% of patients when urine cortisol was used and 28% when urinary 17-hydroxycorticosteroids were used. Serum cortisol after the 1-mg test correlated with baseline urinary free cortisol (r = 0.705, P < 0.001), plasma ACTH level (r = 0.322, P = 0.001), and urinary free cortisol after the 2-d test (r = 0.709, P = 0.001). This study provides evidence that low-dose dexamethasone may suppress either plasma cortisol or urinary steroids to levels previously thought to exclude Cushing's syndrome and that these tests should not be used as the sole criterion to exclude the diagnosis of endogenous hypercortisolism.     

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.     

OVERNIGHT DEXAMETHASONE PRE-TREATMENT IMPROVES THE PERFORMANCE OF THE LYSINE-VASOPRESSIN TEST IN THE DIAGNOSIS OF CUSHING'S SYNDROME

OBJECTIVE There is no endocrine test which is completely reliable for the confirmation of Cushing's syndrome and in separation of the various aetiologies. We have tested the hypothesis that overnight dexamethasone pre-treatment should result in a better performance of the lysine-vasopressin (LVP) test in the diagnosis of Cushing's syndrome. STUDY DESIGN AND PATIENTS We studied 61 subjects, including 25 pituitary-dependent and 9 pituitary independent Cushing's (7 adrenal tumours and 2 ectopic ACTH syndromes), 18 euadrenal controls, 4 depressed subjects, and 5 cushingoid patients. The subjects received 1 mg of dexamethasone orally at 2300 h and the following morning they were given 10 IU of lysine-vasopressin im. MEASUREMENTS Plasma cortisol (RIA) was measured at times ?15, 0, 15, 30, 45, 60, 75, 90 and 120 minutes. RESULTS The dexamethasone-modified LVP (Dx/LVP) test resulted in four patterns of cortisol response. The dexa sensitive pattern (positive suppression and negative response to LVP) was found in euadrenal subjects; the dexa insensitive pattern (negative suppression and positive response to LVP) was seen in Cushing’s disease; a non-responsive pattern (negative suppression and negative response to LVP) was observed only in pituitary independent Cushing's; and an indeterminate pattern (positive suppression and positive response to LVP) was equivocal, being observed in 2 control subjects, 1 patient with Cushing’s disease and 1 depressed patient. In separating control subjects from Cushing's syndromes the Dx/LVP test had 88.9% sensitivity, 100% specificity and 96.2% diagnostic accuracy; when the test was used to segregate Cushing's disease from control subjects we found 96.0% sensitivity, 100% specificity and 97.7% diagnostic accuracy. The performance variables for the Dx/LVP test in separating pituitary dependent from pituitary independent Cushing's were uniformly 100%. Depressed and cushingoid subjects did not differ from control subjects in their cortisol patterns during the test. Successful removal of the pituitary microadenoma in Cushing's disease was invariably followed by a reversal of the abnormal cortisol pattern (dexa insensitive) during the test to a dexa sensitive pattern indistinguishable from that of control subjects. CONCLUSION These results confirm our hypothesis and suggest that an improved performance of any corticotroph stimulus (oCRH, LVP, AVP or desmopressin) in the diagnosis of Cushing's syndrome should result from pre-treatment with dexamethasone.     

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.