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。     

亚临床库欣综合征

典型的库欣综合征是少见疾病 ,而亚临床库欣综合征则较为多见。后者缺乏皮质醇增多症的典型特征 ,而肥胖病、高血压、2型糖尿病的发病率较高。患有亚临床库欣综合征的患者是否实施肾上腺切除术 ,应根据大剂量地塞米松抑制试验的结果 ,对年龄小于 5 0岁的病人、血浆促肾上腺皮质激素较低的病人、近期体重增加、肥胖、高血压、糖尿病和骨质减少症的病人需考虑手术     

亚临床库欣综合征

典型的库欣综合下是少见疾病，而亚临床库欣综合征则较为多见。后者缺乏皮质醇增多症的典型特征，而肥胖病，高血压，2型糖尿病的发病率较高。患有亚临床库欣综合征的患者是否实施肾上腺切除术，应根据大剂量地塞米松抑制试验的结果，对年龄小于50岁的病人，血浆促肾上腺皮质激素较低的病人，近期体重增加，肥胖，高血压，糖尿病和骨质减少症的病人需考虑手术。     

亚临床及肾上腺腺瘤型库欣综合征患者手术前后代谢综合征症状变化

目的 评价肾上腺意外瘤中亚临床库欣综合征及肾上腺腺瘤型库欣综合征患者代谢综合征症状的发生情况及其手术后的变化。方法 检测10例亚临床库欣综合征（组2）及20例典型的。肾上腺腺瘤型库欣综合征（组3）患者的血压、血脂、血尿皮质醇、血ACTH等指标，并行口服糖耐量试验，结果与20例正常对照者（组1）比较。组2及组3所有患者均经手术治疗，术后测值再与术前比较。结果 （1）代谢综合征的患病率组1为10％（2／20），组2为40％（4／10），组3为45％（9／20）。组2与组3腹型肥胖、高血压、糖代谢及脂代谢紊乱的患病率均高于组1，组2及组3糖负荷后2h血糖、收缩压高于组1（均P〈0．05），组3甘油三酯高于组1（P〈0．05）。（2）术后组2及组3患者血、尿皮质醇较术前均下降（均P〈0．05），ACTH则升高（P〈0．05）。组2代谢综合征患者术后有75％（3／4）症状改善，不再符合代谢综合征的诊断标准，相应组3为44．4％（4／9）。两组术后腹型肥胖得以纠正者分别为25％及33．3％，血压恢复正常者分别为33．3％及27．8％，糖代谢改善者分别为50％及63．6％，血脂恢复正常者分别为33．3％及14．3％。结论 亚临床库欣与腺瘤型库欣综合征患者皮质醇分泌升高，导致腹型肥胖、高血压、糖代谢及脂代谢紊乱等代谢综合征症状的患病率升高，手术去除病因后上述症状得以改善。     

老年肾上腺意外瘤诊治特点

随着计算机断层显像(CT)、超声及核磁共振成像技术(MRI)的广泛应用,无症状肾上腺肿瘤的意外检出率逐渐增多,尤其在老年人中。老年肾上腺意外瘤的临床表现多不典型,给临床诊断带来较大困难。肾上腺意外瘤大部分为良性和无功能性肿瘤,也可见功能性和恶性肿瘤。     

肾上腺腺瘤型亚临床库欣综合征患者腺瘤切除术后肾上腺皮质功能减退影响因素及其预测效能

目的 探讨肾上腺腺瘤型亚临床库欣综合征（SCS）患者腺瘤切除术后肾上腺皮质功能减退的影响因素,并分析相关影响因素对术后肾上腺皮质功能减退的预测效能。方法 选择59例肾上腺腺瘤型SCS患者,均行腹腔镜下单侧肾上腺腺瘤切除术,术后1个月根据血清皮质醇水平判断患者是否发生肾上腺皮质功能减退。比较肾上腺皮质功能减退患者与肾上腺皮质功能正常患者的术前一般资料[性别、年龄、身体质量指数（BMI）、入院时血压、代谢合并症（超重/肥胖、高血压、糖脂代谢异常、骨量减少/骨质疏松）、肿瘤直径]、术前肾上腺功能相关激素水平[促肾上腺皮质激素（ACTH）及皮质醇昼夜节律（8:00、24:00）、1 mg地塞米松抑制试验（1 mg-DST）后皮质醇、经典小剂量地塞米松抑制试验（LDDST）后皮质醇、血清硫酸脱氢表雄酮（DHEAS）以及24 h尿游离皮质醇（UFC）]以及术后糖皮质激素用药情况。以组间比较P<0.10的指标构建二元Logistic回归分析模型,分析SCS患者术后肾上腺皮质功能减退的影响因素,采用受试者工作特征（ROC）曲线评估相关指标的预测效能。结果 59例SCS患者中,术后1个月发生肾上腺皮质功能减退25例,发生率为42.37%。与肾上腺皮质功能正常患者比较,肾上腺皮质功能减退患者术前8:00血浆ACTH水平降低,24:00血清皮质醇水平和1 mg-DST后皮质醇水平升高。Logistic回归分析显示,术前1 mg-DST血清皮质醇是SCS患者术后发生肾上腺皮质功能减退的独立影响因素。术前1 mg-DST血清皮质醇≥233 nmol/L的SCS患者术后肾上腺皮质功能减退的相对风险比为13.698(95%CI为2.965～63.274)。结论 SCS患者术后存在发生肾上腺皮质功能减退的风险,术前1 mg-DST血清皮质醇是术后肾上腺皮质功能减退的独立影响因素,对术后肾上腺皮质功能减退发生具有较好的预测效能。     

肾上腺意外瘤69例临床分析

目的提高对肾上腺意外瘤(adrenalincidentaloma,AI)的认识及诊治水平。方法对经手术证实的69例AI患者的临床资料进行分析。结果69例AI患者中,男性33例(47.8%),女性36例(52.2%)。共有38例(55.1%)为健康体检发现。40~60岁为AI发现的高峰年龄,占69.6%。超声、CT、MRI等影像学检查均能有效地检出AI,CT的诊断与术后病理诊断符合率最高(89.9%)。69例患者中恶性病变13例(18.8%),其肿瘤平均直径为6.7±1.9cm,明显大于良性病变组(3.9±2.2cm)(P<0.05);良性病变56例(81.2%)。在39例行肾上腺内分泌功能检查的AI患者中,无功能改变29例(占74.4%),其中以皮质腺瘤为多,有24例(61.5%);有内分泌功能改变10例(25.6%),其中嗜铬细胞瘤5例(12.8%)。结论健康体检时,常规做肾上腺B超等影像学检查能早期发现AI,同时应对其病理性质及内分泌功能进行评估,以指导进一步诊治。     

亚临床库欣综合征患者手术治疗后代谢获益及预测因素分析

目的 明确亚临床库欣综合征(SCS)术后代谢合并症改善情况,探究预测SCS术后代谢改善的因素.方法 回顾性纳人确诊为肾上腺腺瘤型SCS患者144例,根据是否接受手术将其分为手术组(97例)和未手术组(47例);根据不同代谢结局将手术组中术前存在代谢合并症的65例患者再分为代谢改善组(44例)和代谢无改善组(21例).收集所有患者一般临床资料和CT检查结果并分组进行比较.采用logistic回归分析评估术前指标对SCS术后代谢获益的影响因素并得出回归方程,构建列线图评分模型,运用校准图和拟合优度检验校准效能.采用受试者工作特征(ROC)曲线评估模型及相关指标的预测价值.结果 手术组肾上腺肿瘤直径、1mg地塞米松抑制试验(DST)皮质醇、2 mg-DST皮质醇水平及女性、脂代谢异常患者比例均显著高于未手术组,8:00血浆促肾上腺皮质激素(ACTH)及血清硫酸脱氢表雄酮(DHEAS)水平均显著低于未手术组(P＜0.05).代谢改善组术前肾上腺肿瘤直径、1 mg-DST皮质醇水平、术前合并高血压病和合并2种及以上代谢合并症患者比例均显著高于代谢无改善组(P＜0.05).多因素logistic回归分析结果显示,肾上腺肿瘤直径、1 mg-DST皮质醇、合并2种及以上代谢合并症均为SCS术后代谢改善的独立影响因素(P＜0.05).构建列线图评分模型预测SCS术后代谢改善的ROC曲线下面积为0.871,敏感度为75.0％、特异度为90.5％,预测效能优于各指标单独预测.结论 手术治疗后SCS患者代谢结局存在异质性,联合肾上腺肿瘤直径、1 mg-DST皮质醇及是否合并2种及以上代谢合并症的列线图评分模型可预测其术后代谢改善概率.     

肾上腺意外瘤的评估与管理

肾上腺意外瘤(adrenal incidentalomas,AI)的检出率日渐增高。初诊AI时需要结合影像学检查和生化检测评估其良、恶性和有无内分泌功能。恶性或功能性AI患者行手术治疗,未行手术治疗的患者随访观察。规范的AI管理流程是AI正确诊断和治疗的保障。     

Subclinical Cushing's syndrome in patients with adrenal incidentaloma: clinical and biochemical features

Incidentally discovered adrenal masses are mostly benign, asymptomatic lesions, often arbitrarily considered as nonfunctioning tumors. Recent studies, however, have reported increasing evidence that subtle cortisol production and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are more frequent than previously thought. The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas, in relation to their clinical outcome. Fifty consecutive patients with incidentally detected adrenal adenomas, selected from a total of 65 cases of adrenal incidentalomas, were prospectively evaluated. All of them underwent abdominal computed tomography scan and hormonal assays of the HPA axis function: circadian rhythm of plasma cortisol and ACTH, urinary cortisol excretion, 17-hydroxyprogesterone, androgens, corticotropin stimulation test and low-dose (2 mg) dexamethasone test. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 38 months. Subtle hypercortisolism, defined as abnormal response to at least 2 standard tests of the HPA axis function in the absence of clinical signs of Cushing's syndrome (CS), was defined as subclinical CS. Mild-to-severe hypertension was found in 24 of 50 (48%) patients, type-2 diabetes in 12 of 50 (24%), and glucose intolerance in 6 of 50 (12%) patients. Moreover, 18 of 50 patients (36%) were diffusely obese (body mass index, determined as weight/height2, > 25), and 14 patients (28%) had serum lipid concentration abnormalities (cholesterol > or = 6.21 mmol/L, low-density lipoprotein cholesterol > or = 4.14 mmol/L and/or triglycerides > or = 1.8 mmol/L). Compared with a healthy population, bone mineral density Z-score, determined by the DEXA technique, tended to be slightly (but not significantly) lower in patients with adrenal adenoma (-0.41 SD). Endocrine data were compared with 107 sex- and age-matched controls, and patients with adenomas were found to have heterogeneous hormonal abnormalities. In particular, significantly higher serum cortisol values (P < 0.001), lower ACTH concentration (P < 0.05), and impaired cortisol suppression by dexamethasone (P < 0.001) were observed. Moreover, in patients with adenomas, cortisol, 17-OH progesterone, and androstenedione responses to corticotropin were significantly increased (P < 0.001, all), whereas dehydroepiandrosterone sulfate levels were significantly lower at baseline, with blunted response to corticotropin (P < 0.001, both). However, the criteria for subclinical CS were met by 12 of 50 (24%) patients. Of these, 6 (50%) were diffusely obese, 11 (91.6%) had mild-to-severe hypertension, 5 (41.6%) had type-2 diabetes mellitus, and 6 (50%) had abnormal serum lipids. The clinical and hormonal features improved in all patients treated by adrenalectomy, but seemed unchanged in all those who did not undergo surgery (follow-up, 9 to 73 months), except for one, who was previously found as having nonfunctioning adenoma and then revealed to have subclinical CS. In conclusion, an unexpectedly high prevalence of subtle autonomous cortisol secretion, associated with high occurrence of hypertension, diabetes mellitus, elevated lipids, and diffuse obesity, was found in incidentally discovered adrenal adenomas. Although the pathological entity of a subclinical hypercortisolism state remained mostly stable in time during follow-up, hypertension, metabolic disorders, and hormonal abnormalities improved in all patients treated by adrenalectomy. These findings support the hypothesis that clinically silent hypercortisolism is probably not completely asymptomatic.     

Development of overt Cushing's syndrome in patients with adrenal incidentaloma.

OBJECTIVE: The natural course of adrenal incidentalomas, especially those with subclinical autonomous glucocorticoid production, i.e. subclinical Cushing's syndrome, and the risk that such conditions will evolve towards overt Cushing's syndrome are unknown. DESIGN: Longitudinal follow-up evaluation of a series of 284 consecutive patients with adrenal incidentaloma. METHODS AND RESULTS: Out of 284 consecutive patients with adrenal incidentaloma studied at our Institution in the last 15 years, 98 patients (23 with subclinical hypercortisolism) underwent surgery. Of 130 non-operated patients with a follow-up of at least 1 year, eight had subclinical hypercortisolism at diagnosis. We describe in detail four patients who developed overt Cushing's syndrome after 1-3 years of follow-up. Only one of these patients had subclinical hypercortisolism at first diagnosis. Estimated cumulative risk for a non-secreting adrenal incidentaloma to develop subclinical hyperfunction was 3.8% after 1 year and 6.6% after 5 years. For patients with masses with subclinical autonomous glucocorticoid overproduction, estimated cumulative risk to develop overt Cushing's syndrome was 12.5% after 1 year. CONCLUSIONS: In patients with adrenal incidentalomas the risk of progression towards overt Cushing's syndrome is not low, at variance with previous reports. A careful biochemical and hormonal follow-up is advisable in all patients who do not need surgery at first presentation.     

Subtle glucocorticoid excess in patients with adrenal incidentaloma.

Incidentally discovered adrenal tumors (incidentalomas) are fairly common since the advent of noninvasive methods of imaging the abdomen. Patients with incidentaloma usually undergo screening for overproduction of glucocorticoids by measurement of basal steroid excretion. We describe an asymptomatic patient with an incidentaloma with normal basal steroid excretion whose only manifestation of subtle steroid overproduction was the failure of steroid excretion to be suppressed normally with dexamethasone. It appears tht the more careful the search for subtle evidence of steroid overproduction in patients with incidentaloma, the more common the finding; perhaps up to 50% of patients with incidentaloma have some subtle steroid overproduction. We review the literature on this subject, and evaluate the various possible approaches of how intensively to study steroid dynamics in patients with incidentaloma.     

Influence of adrenal subclinical hypercortisolism on hypertension in patients with adrenal incidentaloma

OBJECTIVE: The purpose of our study was to clarify whether subtle cortisol-producing tumors, such as not only subclinical Cushing's syndrome (SubCS) but also subclinical hypercortisolism (SH), influence the prevalence of hypertension, since numerous basic research studies have noted that glucocorticoid excess influences blood pressure. METHODS: 80 patients with adrenocortical adenomas (39 women and 41 men; mean age 62.1 years) were enrolled. SubCS was diagnosed using a diagnostic criteria, and SH was diagnosed as the presence of a serum cortisol level greater than 50 nmol/L following 1-mg dexamethasone suppression test (DST). Results: SubCS, SH, or non-functioning adrenocortical adenoma (NF) was diagnosed in 14, 13, or 53 patients, respectively. The prevalence of hypertension differed significantly among the diagnoses (SubCS, 78.6%; SH, 84.6%; NF, 39.6%; P=0.002), whereas no differences in other clinical characteristics such as age, sex, or waist girth were observed. The patients with SH had an 11.7-fold increased risk (95% confidence interval: 1.9-72.7, P=0.009) and those with SubCS had a 9.5-fold increased risk (95% confidence interval: 1.9-48.3, P=0.007) for hypertension compared to those with NF using a multivariate analysis. Conclusion: We demonstrated that subtle cortisol-producing tumors, such as SH as well as SubCS, were an independent risk factor for hypertension. The cut-off value of the 1-mg DST would be appropriate to predict the development of hypertension.     

Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma.

It is known that either chronic glucocorticoid administration or endogenous hypercortisolism frequently induce an hypercoagulable condition. Since little is known about the evaluation of markers of haemostatic and fibrinolytic systems in other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1), tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and vWF-Ag levels did not significantly differ from those found in 50 age- and sex-matched controls, while mean fibrinogen levels were significantly higher in patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl). Patients with adrenal incidentaloma showed PAI-1, t-PA and vWF-Ag mean levels superimposable to those in controls, while fibrinogen (319.7+/-27.9 mg/dl) was slightly, although not significantly, higher than in normals. Considering the limits of normal values (as mean+/-2 SD) obtained in the control group, high PAI-1 levels were found in 2 patients with Cushing's syndrome and in 3 patients with incidentaloma. An elevation of fibrinogen levels was found in 3 patients with Cushing's syndrome and in 3 with incidentaloma. Increased vWF-Ag levels were found only in 1 patient with Cushing's syndrome. An increased t-PA level was occasionally observed only in the patient with adrenal carcinoma. On the whole, an alteration of at least one of haemostatic and fibrinolytic parameters was detected in 55% of the patients with Cushing's syndrome and in 42% of those with adrenal incidentaloma. In conclusion, early alterations of coagulation and fibrinolytic systems may be found in some patients with adrenal disorders, thus suggesting the opportunity of an accurate follow-up in order to identify possible risk factors for cardiovascular disease and thromboembolism.