ACTH非依赖性大结节样肾上腺增生

探讨促肾上腺皮质激素（ACTH）非依赖性大结节样肾上腺增生（AIMAH）的临床和病理特点。AIMAH是不依赖ACTH的库欣综合征，血浆ACTH水平低，大剂量地塞米松抑制试验不被抑制。CT示双侧肾上腺结节样增大，病理改变为双侧肾上腺结节样或腺瘤样增生，双侧肾上腺切除术后不发生Nelson综合征，AIMAH有特殊的临床病理特点，是库欣综合征的一种病因。     

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.     

ACTH非依赖性大结节样肾上腺增生

探讨促肾上腺皮质激素(ACTH)非依赖性大结节样肾上腺增生(AIMAH)的临床和病理特点。AIMAH是不依赖ACTH的库欣综合征,血浆ACTH水平低,大剂量地塞米松抑制试验不被抑制。CT示双侧肾上腺结节样增大,病理改变为双侧肾上腺结节样或腺瘤样增生,双侧肾上腺切除术后不发生Nelson综合征。AIMAH有特殊的临床病理特点,是库欣综合征的一种病因。     

库欣综合征高血压临床特点的研究

目的：研究库欣综合征高血压的临床特点。方法：回顾性研究我院1983年至1999年术后明确病理诊断和库欣综合征184例，其中垂体小腺瘤90例，垂体大腺瘤19例，垂体增生10例；肾上腺腺瘤59例；ACTH非依赖性大结节样肾上腺增生3例；异位ACTH综合征3例。结果库欣综合征高血压患病率为89．7％（按旧标准为82．6％）。在库欣综合征中高血压并发症病率为44．8％。logistic回归分析显示高血压并发症与库欣综合征手术时年龄及最高收缩压独立相关。诊断年龄≤25岁和＞25岁的两组病人，高血压特点差异有显著性。术前使用降压药的129例患者中，术后继续用降压药者仅43例，术后降压药的使用率较术前显著下降（P＜0．001）。结论：在库欣综合征中高血压患病率极高。手术时年龄大及最高收缩压较高者有高血压并发症的可能性大。成人库欣综合征患者高血压患病率更高，血压水平更高，病程更长，更难以控制，更多的合并高血压并发症。大部分库欣综合征患者术后可停用降压药，部分患者术后存在持续性高血压，对术后病人仍要注意高血压的治疗。     

肺部肿瘤致异位ACTH综合征7例报告并文献复习

目的探讨肺部肿瘤致异位促肾上腺皮质激素（ACTH）综合征的临床特点。方法回顾性分析2000年11月～2009年12月解放军总医院内分泌科收治并确诊的7例肺部肿瘤致异位ACTH综合征患者的临床资料。结果高血压、糖尿病、低血钾、水肿为最常见的临床表现,多缺乏典型库欣综合征的体征;血ACTH和皮质醇、24 h尿游离皮质醇水平升高,皮质醇分泌均不被小剂量及大剂量地塞米松抑制试验所抑制;胸部薄层CT扫描能发现多数肺部病变;手术切除肺部病变、小细胞肺癌化疗效果较好;肾上腺切除为控制高皮质醇血症的有效手段。结论肺部肿瘤是导致异位ACTH综合征的常见病因,对于ACTH依赖性库欣综合征的患者应常规行胸部薄层CT来筛查肺部病变。     

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。     

RU486 对正常人和库欣综合征患者垂体-肾上腺轴的影响及其临床应用

本文观察了１０例正常人和１４例库欣综合征患者垂体肾上腺轴在单次口服ＲＵ４８６４ｍｇ／ｋｇ后的反应。正常人在８ｐｍ口服ＲＵ４８６后连续２天８Ａｍ的血促肾上腺皮质激素（ＡＣＴＨ）和皮质醇（Ｆ）均明显升高（Ｐ＜０．０１，Ｐ＜０．００１），服药后第一天２４ｈ尿Ｆ亦明显升高（Ｐ＜０．００１）。库欣综合征组服药后连续观察２天上述激素水平无明显改变。正常组服药后连续２天的血Ｆ，ＡＣＴＨ及２４ｈ尿Ｆ较服药前所增加的百分比均明显高于库欣综合征组（Ｐ＜０．０５）。正常人和库欣综合征患者的垂体肾上腺轴对ＲＵ４８６有明显不同的反应。我们认为一次法ＲＵ４８６激发试验诊断库欣综合征优于小剂量地塞米松抑制试验，可能有临床应用价值。     

非ACTH依赖性肾上腺皮质大结节增生症

目的 探讨非ACTH依赖性双侧肾上腺皮质大结节增生症(AIMAH)的临床特点。方法 分析4例AIMAH临床和实验室资料，结合有关文献进行讨论。结果 4例AIMAH均有库欣综合征的临床表现及生化异常，实验检查显示血浆AcTH水平低下，皮质醇分泌节律紊乱，小剂量、大剂量地塞米松抑制试验均不被抑制，CT检查示双侧肾上腺明显增大呈结节样改变。结论 AIMAH是库欣综合征中病因独特的临床亚型，有其特有的临床特点及病理改变。     

2022年亚临床库欣综合征专家指导建议

亚临床库欣综合征较库欣综合征更常见, 指生化检查皮质醇增多而无特异性的典型库欣综合征临床表现, 可以导致多种代谢异常, 临床上易忽视而相关研究较少, 需要重视和规范诊治。亚临床库欣综合征常见于肾上腺意外瘤患者。对于肾上腺或垂体意外瘤以及与年龄、体重不匹配的骨代谢异常或经规范治疗后糖尿病、高血压和脂代谢控制不佳的患者, 应进行亚临床库欣综合征筛查。初筛首选1 mg过夜地塞米松抑制试验, 确诊试验为小剂量地塞米松抑制试验。诊断后再根据促肾上腺皮质激素水平, 结合影像学和其他功能试验进一步明确病变部位及病因。符合手术指征的肾上腺瘤亚临床库欣综合征患者, 手术后获得最佳代谢改善。围手术期需进行糖皮质激素补充, 术后糖皮质激素替代应个体化。所有患者均应进行定期随访。     

异位ACTH综合征与垂体性库欣病的鉴别诊断

临床显示,异位促肾上腺皮质激素（ACTH）综合征患者血浆ACTH水平较垂体肿瘤高,同时对由于其垂体ACTH分泌受到抑制,由垂体外肿瘤产生的ACTH一般不被大剂量地塞米松抑制。甲吡酮抑制皮质醇合成时,垂体ACTH腺瘤ACTH分泌增加,而分泌ACTH的位肿瘤不出现此种反应,促肾上腺皮质激素放激素（CRH）可刺激大多数垂体腺瘤患者的ACTH释放,但在异位ACTH综合征患者则无此作用,异位分泌ACTH肿瘤检测常依赖于胸腹部CT及MRI。依赖垂体ACTH的库欣病患者垂体附近ACTH浓度较被稀释的周围静脉中ACTH高,故亦可用两者比值（IPS／P）对两种疾病鉴别。     

Reliability of the diagnostic tests for Cushing’s syndrome performed in a tertiary referral center

The study aimed to retrospectively evaluate the reliability of the diagnostic and location tests in Cushing’s Syndrome (CS). Eighty-seven patients diagnosed with CS between 1995 and 2007 by Endocrinology Metabolism Department of Cerrahpasa Medical School were included in the study. The control group consisted of 91 patients who presented to the outpatient clinic because of obesity. The diagnostic tests were as follows: 1 mg dexamethasone suppression test (DST), 24-h urinary free cortisol (UFC), midnight cortisol level (MCL), ACTH level and overnight 8 mg DST. The sensitivity and specificity of UFC were 81 and 66 % respectively for the cut-off point of 50 μg/day, whereas they were 64 and 76 % respectively for the cut-off point of 100 μg/day. For the cut-off value of 1.8/μg/dL for MCL and 1 mDST, the sensitivity rates were 100 and 98 %, while the specificity rates were 88 and 33 %, respectively. Among the location tests, the sensitivity and specificity of ACTH under 10 pg/mL for adrenal CS were 92 and 94 % respectively. The sensitivity and specificity of ACTH higher than 30 pg/mL for ACTH-dependent CS were 69 and 100 % respectively. The sensitivity rates of 8 mg DST for 50 and 60 % suppressions were 83 and 79 % respectively, whereas the specificity rates were 75 and 88 % respectively. 1 mg DST (cut-off <1.8 μg/dL) and UFC (50 μg/24 h) are appropriate tests for screening CS. Overnight 8 mg DST with 60 % suppression for Cushing’s Disease (CD) and ACTH levels <10 pg/mL for adrenal CS, ACTH levels >30 pg/mL for ACTH dependency were identified as the best tests for the differential diagnosis of the subtypes.     

Cost-effectiveness and accuracy of the tests used in the differential diagnosis of Cushing's syndrome.

Aim: Establish the minimal biochemical and radiological examinations necessary and their cost-effectiveness to accurately diagnose the etiology of Cushing's syndrome (CS).Material and Methods: In 71 patients with CS followed between 1982 and 1997 biochemical studies (basal ACTH, 8mg dexamethasone suppression test -HDST-, metyrapone stimulation test -MST-, or inferior petrosal sinus catheterization sinus catheterization -IPSC-) and radiological investigations (abdominal CT scan, pituitary CT scan or MRI) were performed. Once pathology confirmed the diagnosis (48 pituitary Cushing's disease-CD, 17 adrenal neoplasms, 2 bilateral macronodular hyperplasia -BMH-, and 4 ectopic ACTH syndrome -ES-), the sensitivity, specificity, positive and negative predictive value of the different studies was calculated to establish the most accurate and cost-effective diagnostic protocol.Results: In ACTH-independent CS (ACTH 9 pg/ml; normal 9 to 54) a unilateral tumor was identified on abdominal CT scanning in 17, and BMH in 1; the other BMH had detectable ACTH (43.2 pg/ml). In ACTH-dependent CS, ACTH was > 9 pg/ml and IPSC (performed in 22) correctly identified 20 patients with CD and differentiated them from 2 with an ES (100 % specificity and sensitivity). Pituitary MRI or CT did not disclose an adenoma in 41.7% of patients with CD, and was reported to exhibit a microadenoma in 2 of the 4 patients with ES. HDST and MST were of no additional use in the differentiation between CD and ES.Conclusions: Once CS is diagnosed low ACTH and an abdominal CT scan correctly identified all patients of adrenal origin. In ACTH-dependent CS IPSC was the best predictive test to differentiate CD from ES. BMH may behave as ACTH-dependent or independent. The other biochemical and radiological studies performed are not cost-effective and may even be misleading, and should not be routinely performed.     

Imaging in Cushing's syndrome

Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80% of CS is due to ACTH-dependent causes and 20% due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas.     

Coexistence of pituitary adrenocorticotropin-dependent Cushing's syndrome with a solitary adrenal adenoma

A 45-yr-old woman presented with a 2-hr history of Cushing's syndrome. Baseline cortisol and ACTH levels were elevated and lacked a normal circadian rhythm. Dynamic testing of her pituitary-adrenal function revealed positive responses to metyrapone and synthetic ACTH and suppression with high doses of dexamethasone. The finding of asymmetrical adrenal uptake of 6-[131I]methyl-19-nor-cholesterol and a tumor image in the right adrenal on venography led to the preoperative diagnosis of pituitary ACTH-dependent adrenal hyperfunction coexisting with a right adrenal adenoma. Surgical resection of the right adrenal demonstrated a solitary 39-g nodule, 4 cm in diameter. There were no additional nodules present in the surrounding cortex. When incubated in vitro, both the adenoma and the surrounding tissue were functional and responsive to ACTH. This was in contrast to the lack of response to ACTH in vitro of similar tissues removed from two other patients with ACTH-independent adrenal adenomas. We suggest that this case represents a transition between pituitary ACTH-dependent bilateral adrenocortical hyperfunction and solitary adrenal adenoma.     

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。     

22例皮质醇增多症的临床研究

目的：探讨皮质醇增多症的临床表现和内分泌检查等辅助检查的意义.方法：从年龄、性别、病程及实验室检查等方面,观察22例不同原因所致皮质醇增多症患者不同的临床表现和测定实验室检查指标.结果：22例中诊断库欣病（增生型）14例[63.6％,其中13例（92.9％）得到MRI检查证实],肾上腺腺瘤6例[27.3％,均得到MRI检查证实（100％）],另有肾上腺结节样增生1例（4.5％）,异位ACTH综合征1例（4.5％）.临床表现：按出现的频率前4位依次为,库欣病：高血压（100％）、满月脸（92.9％）、向心性肥胖（85.7％）、多血质（85.7％）,肾上腺腺瘤：高血压（100％）、满月脸（100％）、向心性肥胖（100％）、多血质（83.3％）.实验室检查：小剂量地塞米松不能抑制：库欣病与肾上腺腺瘤均为100％.结论：根据高血压、满月脸、向心性肥胖,小剂量地塞米松抑制试验和MRI检查可诊断绝大多数皮质醇增多症.     

Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.     

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。     

双侧岩下窦静脉取血联合去氨加压素刺激试验诊断库欣病的价值

目的 探讨双侧岩下窦静脉取血(BIPSS)过程中联合去氨加压素(DDAVP)刺激试验在库欣病诊断中的意义.方法 16例垂体MRI未见明确肿瘤的ACTH依赖性库欣综合征患者行大剂量地塞米松抑制试验、BIPSS联合DDAVP刺激试验等检查.DDAVP刺激前及刺激后5 min、10 min测定岩下窦静脉与外周静脉血ACTH的比值.比值＞2者考虑库欣病.比较DDAVP刺激的BIPSS及大剂量地塞米松抑制试验和术后诊断的一致性.结果 16例库欣病患者中9例(56.3％)大剂量地塞米松试验可抑制,BIPSS联合DDAVP试验中DDAVP刺激前12例(75.0％)岩下窦静脉与外周静脉血ACTH的比值＞2;刺激后14例(87.5％)患者比值＞2.介入手术过程中未出现明显严重不良反应.结论 BIPSS联合DDAVP刺激试验可用于指导影像学检查无明确结果的库欣病患者的鉴别诊断和治疗.     

Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis

The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.