16例异位ACTH综合征的临床特点分析

目的 通过分析异位ACTH综合征的临床特点,加深对其的认识,提高诊治水平.方法 回顾性分析解放军总医院2000-2009年确诊的16例异位ACTH综合征患者的临床资料.结果 (1)异位ACTH综合征最常见的病因为肺部肿瘤及胸腺类癌;(2)临床表现以糖代谢异常、高血压、低血钾、下肢水肿最为突出;(3)实验室检查提示血皮质醇、促肾上腺皮质激素(ACTH)及24 h尿游离皮质醇(24hUFC)水平显著升高及严重的低血钾碱中毒;(4)大剂量地塞米松抑制试验、促肾上腺皮质激素释放激素(CRH)兴奋试验及岩下窦取血测定岩下静脉血ACTH与外周静脉血ACTH的比值对定性诊断具有较高价值;(5)X线胸片、胸部CT能发现大多数原发病灶;(6)手术切除原发肿瘤病灶是首选治疗方法.结论 异位ACTH综合征诊断困难,其治疗应首选手术切除原发肿瘤.     

16例异位ACTH综合征的临床特点分析

目的 通过分析异位ACTH综合征的临床特点,加深对其的认识,提高诊治水平.方法 回顾性分析解放军总医院2000-2009年确诊的16例异位ACTH综合征患者的临床资料.结果 (1)异位ACTH综合征最常见的病因为肺部肿瘤及胸腺类癌;(2)临床表现以糖代谢异常、高血压、低血钾、下肢水肿最为突出;(3)实验室检查提示血皮质醇、促肾上腺皮质激素(ACTH)及24 h尿游离皮质醇(24hUFC)水平显著升高及严重的低血钾碱中毒;(4)大剂量地塞米松抑制试验、促肾上腺皮质激素释放激素(CRH)兴奋试验及岩下窦取血测定岩下静脉血ACTH与外周静脉血ACTH的比值对定性诊断具有较高价值;(5)X线胸片、胸部CT能发现大多数原发病灶;(6)手术切除原发肿瘤病灶是首选治疗方法.结论 异位ACTH综合征诊断困难,其治疗应首选手术切除原发肿瘤.     

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。     

异位ACTH综合征和库欣病伴低血钾临床特点的比较

目的　研究异位ACTH综合征的临床特点 ,提高早期诊断和降低误诊、误治率。方法　回顾性分析我院 1998年 1月～ 2 0 0 3年 2月收治的异位ACTH综合征的临床特点、影像学检查在诊断过程中的作用 ,并与低血钾库欣病进行比较。结果　 (1)异位ACTH综合征占同期皮质醇增多症的 11.3 % ,常见病因是肺癌和支气管类癌 ;(2 )异位ACTH综合征多见于男性 (M :F =5 :3 ) ,确诊时年龄大 ,病程在 5个月之内 ,病情进展快 ,常常伴有肌萎缩和肌无力 ,下肢水肿 ;(3 )血清ACTH和血浆皮质醇 (F)水平更高 ,大剂量地塞米松抑制试验阴性率更高 ,代谢性碱中毒更严重 ;(4 )胸部平片和CT检查能发现多数病变 ;(5 )预后取决于肿瘤的性质 ,手术完全切除病灶是关键。结论　综合临床特点、动脉血气、血清钾和激素水平、胸部平片及CT检查有助于鉴别异位ACTH综合征和库欣病伴低血钾     

论著外周DDAVP兴奋试验在促肾上腺皮质激素依赖性库欣综合征鉴别诊断中的价值

目的 评价外周1-脱氨-8-精氨酸血管加压素(DDAVP)兴奋试验,在促肾上腺皮质激素(ACTH)依赖性库欣综合征鉴别诊断中的价值。方法 回顾性分析2012年1月至2013年6月在北京协和医院诊断明确的ACTH依赖性库欣综合征患者的临床资料,包括外周DDAVP兴奋试验、岩下窦静脉取血、鞍区MRI和手术病理的结果,评价外周DDAVP兴奋试验对诊断垂体ACTH腺瘤的敏感度和特异度。另收集10例文献报告的异位ACTH肿瘤患者资料,纳入统计分析。通过比较岩下窦静脉取血和外周DDAVP兴奋试验结果的差异,分析外周DDAVP兴奋试验中ACTH不升高的原因和此项检查的局限性。结果 (1)共纳入41例ACTH依赖性库欣综合征患者,其中28例为垂体ACTH腺瘤(简称库欣病),13例为异位分泌ACTH肿瘤。(2)如以ACTH升高到基础值1.5倍作为阳性反应标准,82%(23/28)库欣病和38%(5/13)的异位ACTH肿瘤患者可达到此反应。如以ACTH升高到基础值3倍为反应标准,50%(14/28)的库欣病患者达此标准,而异位ACTH肿瘤为0(0/13)。(3)有12例库欣病患者同时进行岩下窦静脉取血。其中7例外周DDAVP试验中ACTH水平未达到基础值的3倍,但岩下窦ACTH水平在DDAVP刺激后明显升高。结论 外周DDAVP兴奋试验有助于ACTH依赖性库欣综合征的鉴别诊断。ACTH升高幅度越大,越支持库欣病的诊断。如ACTH升高到基础值3倍以上,可确诊为库欣病。     

异位ACTH综合征6例临床分析

目的提高临床医生对异位ACTH综合征的认识。方法对四川大学华西医院1996—2005年确诊的6例异位ACTH综合征患者的临床资料及诊治过程进行回顾性分析。结果副节瘤1例,神经内分泌癌1例,肺癌4例。临床特征病程15d至2个月,6例患者均有严重低血钾伴碱中毒,5例患者有高血压和双下肢水肿。Cushing综合征表现满月脸4例,淤斑和长胡须2例,多血质、痤疮、色素沉着各1例,血皮质醇(晨起8时)>1173nmol/L,大剂量地塞米松(8mg)抑制试验均不能抑制。结论对病程短,严重低血钾碱中毒,水肿明显而Cushing临床表现不明显者,血皮质醇>1000nmol/L应高度怀疑异位ACTH综合征。寻找病因,尽快手术切除肿瘤,近期预后较好。     

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的异位肿瘤不出现此种反应。促肾上腺皮质激素释放激素 (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。     

以躁狂发作为首发症状的异位促肾上腺皮质激素综合征1例报告并文献复习

正异位促肾上腺皮质激素(ACTH)综合征(ectopic ACTH syndrome,EAS)是库欣综合征中的少见类型,临床诊断较为困难,由于皮质醇水平增高可导致认知、记忆、情感等方面的异常,当以急性精神异常为首发表现时原发疾病易被忽略,造成误诊误治。本文报道了一例以躁狂发作为首发症状的异位ACTH综合征患者完整的诊治及随访经过,并对该类疾病导致的精神异常进行文献复习,希望有助于提高临     

促肾上腺皮质激素测定的临床价值

测定血浆促肾上腺皮质激素(ACTH)的最大价值在于鉴别皮质醇增多症(柯兴氏综合征)的病因。因为从肾上腺肿瘤患者的血浆中不能检出ACTH,而在垂体性皮质醇增多症和异位ACTH分泌综合征患者的血浆中却可检出ACTH。未经治疗的垂体性皮质醇增多症患者,血浆ACTH水平早晨在正常范围内(但24小时分泌的正常波动周期消失)或略有增高(即在200微微克/毫升以上),异位ACTH分泌综合征患者,血浆ACTH水平常显著升高。由于许多垂体性皮质醇增多症者早晨血浆ACTH水平正常,因此,除非血浆ACTH水平很高,否则,单     

异位ACTH综合征6例临床分析

目的 提高临床医生对异位ACTH综合征的认识。方法 对四川大学华西医院1996-2005年确诊的6例异位ACTH综合征患者的临床资料及诊治过程进行回顾性分析。结果 副节瘤1例，神经内分泌癌1例，肺癌4例。临床特征：病程15d至2个月，6例患者均有严重低血钾伴碱中毒，5例患者有高血压和双下肢水肿。Cushing综合征表现：满月脸4例，淤斑和长胡须2例，多血质、痤疮、色素沉着各1例，血皮质醇（晨起8时）〉1173nmol／L，大剂量地塞米松（8mg）抑制试验均不能抑制。结论 对病程短，严重低血钾碱中毒，水肿明显而Cushing临床表现不明显者，血皮质醇〉1000nmol／L应高度怀疑异位ACTH综合征。寻找病因，尽快手术切除肿瘤，近期预后较好。     

The ovine corticotropin-releasing hormone (CRH) stimulation test is superior to the human CRH stimulation test for the diagnosis of Cushing's disease

The ovine CRH (oCRH) stimulation test is useful in distinguishing Cushing's disease from the syndrome of ectopic ACTH secretion. Most patients with Cushing's disease have increased plasma ACTH and cortisol responses to oCRH, while patients with the ectopic ACTH syndrome do not. We predicted that the homologous hormone human CRH (hCRH) might be an equally useful diagnostic agent, with the theoretic advantage of being less immunogenic. This study compared the responses to hCRH and oCRH (1 microgram/kg, iv) in 15 patients with Cushing's disease. Plasma ACTH and cortisol levels increased in most patients during the first hour after administration of either hCRH or oCRH. However, the peak and time-integrated hormonal responses to hCRH were smaller than the responses to oCRH. All but 1 patient had an ACTH and/or cortisol response to oCRH that exceeded 4 times the intraassay coefficient of variation. Three patients had neither an ACTH nor a cortisol response to hCRH by the same criterion. Thus, when administered at equivalent doses, hCRH is a less effective stimulus of ACTH and cortisol secretion in patients with Cushing's disease. Based upon the observation that the oCRH stimulation test has greater sensitivity than the hCRH stimulation test for the diagnosis of Cushing's disease, we conclude that oCRH is the preferred analog to use for CRH testing in patients with Cushing's syndrome.     

高血糖、低血钾伴胰腺肿瘤

中年男性患者 ,以高血糖、严重低血钾入院。伴消瘦、皮肤薄、脸圆 ,精神症状。CT示胰腺肿瘤 ;垂体无异常。结合血尿皮质醇、血ACTH、地塞米松抑制试验结果拟诊为异位ACTH综合征。本文就此病的诊断、鉴别及治疗进行了讨论。     

The ovine corticotropin-releasing hormone stimulation test and the dexamethasone suppression test in the differential diagnosis of Cushing's syndrome

We gave a standard dexamethasone suppression test and an ovine corticotropin-releasing hormone (CRH) stimulation test to 41 patients with adrenocorticotrophic hormone (ACTH)-dependent hypercortisolism to determine the efficacy of each test in the differential diagnosis of Cushing's syndrome. Twenty-nine of thirty-three patients with Cushing's disease and 0 of 8 patients with ectopic secretion of ACTH responded to the ovine CRH test with increased levels of cortisol. When a cortisol response was judged as positive for Cushing's disease, the CRH test had a diagnostic sensitivity, specificity, and accuracy of 88%, 100%, and 90%, respectively. Twenty-nine patients with Cushing's disease and 1 patient with ectopic secretion of ACTH responded to the dexamethasone suppression test. A combined-test strategy requiring negative results from both tests to exclude a diagnosis of Cushing's disease yielded superior sensitivity (100%) and diagnostic accuracy (98%). Thus, the ovine CRH test works as well as the standard dexamethasone suppression test in discriminating between Cushing's disease and ectopic ACTH secretion. The diagnostic power of each test is enhanced when the two tests are combined.     

Ectopic Cushing's syndrome due to concurrent corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secreted by malignant gastrinoma.

Ectopic Cushing's syndrome due to various malignancies is not uncommon. However, a few cases of ectopic Cushing's syndrome caused by corticotropin-releasing hormone (CRH), or CRH with adrenocorticotropic hormone (ACTH) have been reported. A 28-year-old woman presented with acute upper gastrointestinal bleeding caused by an active ulcer, located atypically in the 2nd portion of duodenum. Further work-up revealed high gastrin levels and abdominal computed tomography (CT) scans showed a large pancreatic head mass with multiple liver metastases. The serum cortisol and ACTH levels were checked due to hypokalemia with metabolic alkalosis and recent amenorrhea. Cortisol and ACTH were both highly elevated with pituitary hyperplasia and elevated CRH. The existence of ectopic ACTH and CRH in the liver biopsy was also demonstrated immunohistochemically. Since an operation was not feasible, chemotherapy was conducted using paclitaxel and etoposide. These two drugs were chosen according to the IN VITRO chemotherapy response assay to maximize the treatment. This report demonstrates concurrent ACTH- and CRH-related ectopic Cushing's syndrome caused by malignant gastrinoma with multiple liver metastases that was treated with marginal success using a multidisciplinary medical approach.     

Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide

The long-acting somatostatin analog (octreotide) was administered to a 37-yr-old woman with the ectopic ACTH syndrome. The patient had diffuse metastatic spread of a nonpituitary tumor, presumably of pancreatic origin, and severe and rapidly progressive hypercortisolism with extreme myopathy, hypokalemia, and diabetes mellitus. Plasma ACTH and lipotropin levels and 24-h urinary cortisol excretion were greatly elevated [218 pg/mL (48 pmol/L), 1340 pg/mL (220 pmol/L), and up to 830 micrograms/24 h (2290 nmol/day), respectively]. Urinary cortisol excretion decreased to normal within 3 days after the initiation of octreotide therapy (150, 300, and 600 micrograms/day), and plasma ACTH and lipotropin levels also decreased. Urinary cortisol excretion remained normal for 2 months during chronic octreotide therapy, and her general condition improved dramatically. The only side-effect was a slight increase in the number of bowel movements. Tumor progression, however, was not controlled, and she eventually died of hepatic insufficiency. These data indicate that octreotide can be a highly effective treatment for patients with the ectopic ACTH syndrome.     

Cushing's syndrome due to a pulmonary carcinoid

Cushing paraneoplasic syndrome is a rare cause of hypercorticism. We report a case of 35 year-old man presenting with Cushing's syndrome characterized by severe signs of hypercorticism and hypokalemia. Endocrine investigations were suggestive of an hypercortisolism linked to an ectopic adrenocorticotropic (ACTH) secretion, both at baseline (mean ACTH levels=275 pg/ml, urinary free cortisol excretion=3.898 mmol/24 h) and after pharmacodynamic testing (lack of inhibition of ACTH by dexamethasone). Thoracic tomodensitometric examination revealed a 15 mm tumor corresponding to a neuroendocrine pulmonary carcinoid with positive immunostaining for chromogranin A. Postoperative ACTH measurement was undetectable, plasma cortisol and free urinary cortisol were also decreased after tumor resection suggesting complete tumor removal. This case report illustrates the characteristics of paraneoplasic Cushing syndrome due to ACTH secreting pulmonary neuroendocrine carcinoid.     

Ectopic ACTH syndrome associated with large-cell neuroendocrine carcinoma of the lung

Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well-known paraneoplastic phenomenon, an association with large-cell neuroendocrine carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He did not have a typical Cushingoid appearance nor used diuretics. His newly noted hypertension, hypokalemia (plasma potassium (K) concentration 1.8 mEq/L) with renal K wasting, and metabolic alkalosis suggested a state of mineralocorticoid excess. His plasma renin activity and aldosterone concentrations were low, but cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His hypokalemia and hypertension were controlled with spironolactone and K supplementation. This is the first reported case of EAS in LCNEC and should be kept in mind as a cause of hypokalemia in lung cancer patients.     

NIH conference. Clinical applications of corticotropin-releasing factor

Ovine and human corticotropin-releasing factors (CRF) have similar potencies in causing adrenocorticotropic hormone (ACTH) and cortisol secretion in normal humans. Using long-acting ovine CRF (1 microgram/kg body weight as an intravenous bolus), we tested patients with Cushing's syndrome, adrenal insufficiency, and psychiatric conditions with mild hypercortisolism. Over 95% of hypercortisolemic patients with a pituitary adenoma responded with increases in plasma ACTH and cortisol concentrations; patients with the ectopic ACTH syndrome had no ACTH or cortisol responses; patients with ACTH-independent hypercortisolism of adrenal origin had low or undetectable plasma ACTH concentrations before and after CRF without any cortisol response. The differences in responses of patients with adrenal insufficiency of primary, pituitary, or suprapituitary type likewise suggest value of the CFR test in their differential diagnosis. The responses in the psychiatric patients should permit differentiation between Cushing's syndrome and hypercortisolism of psychiatric origin.