Cushing's syndrome caused by giant Ewing's sarcoma of the kidney:A case report and review of literature

BACKGROUND Primary renal Ewing’s sarcoma(ES)is extremely rare,and only two cases causing Cushing’s syndrome(CS)have been reported to date.We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes,weight gain,and hypertension.CASE SUMMARY CS was first diagnosed by laboratory testing.A huge tumor was revealed in the kidney following an imaging examination.Moreover,brain and bone metastases were observed.After comprehensive treatment,primarily based on surgery,primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing.Furthermore,the glucocorticoid level returned to normal.By the ninth postoperative month of follow-up,the patient was recovering well.Cushing-related symptoms had improved,and a satisfactory curative effect was achieved.CONCLUSION Primary renal ES,a rare adult malignant tumor,can cause CS and a poor prognosis.

Cushing’s syndrome caused by an ACTH-producing large cell neuroendocrine carcinoma of the gallbladder

Malignancies of the gallbladder, including neuroendocrine tumors, are uncommon, mostly found incidentally after cholecystectomy and are frequently asymptomatic in the early stages, but highly fatal. Limited data is available on adrenocorticotropic hormone (ACTH) producing neuroendocrine tumors specifically originating from the gallbladder. We report the clinical and radiographic findings, which included positron emission tomography and computed tomography, of a patient with a gallbladder mass who presented with Cushing’s syndrome. Subsequently, a diagnosis of ACTH-producing large cell neuroendocrine carcinoma of the gallbladder was made. Despite being rare and having a poor prognosis, hormone-producing neuroendocrine tumors should be part of the differential diagnosis in the approach of patients with Cushing’s syndrome.

Primary aldosteronism due to bilateral micronodular hyperplasia and concomitant subclinical Cushing’s syndrome:A case report

BACKGROUND Adrenal incidentaloma(AI)has been frequently encountered in the clinical setting.It has been shown that primary aldosteronism(PA)or subclinical Cushing’s syndrome(SCS)are the representative causative diseases of AI.However,the coexistence of PA and SCS has been reportedly observed.Recently,we encountered a case of AI,in which PA and SCS coexisted,confirmed by histopathological examinations after a laparoscopic adrenalectomy.We believe that there were some clinical implications in the diagnosis of the present case.CASE SUMMARY A 58-year-old man presented with lower right abdominal pain with a blood pressure of 170/100 mmHg.A subsequent computed tomography scan revealed right ureterolithiasis,which was the cause of right abdominal pain,and right AI measuring 22 mm×25 mm.After the disappearance of right abdominal pain,subsequent endocrinological examinations were performed.Aldosterone-related evaluations,including adrenal venous sampling,revealed the presence of bilateral PA.In addition,several cortisol-related evaluations showed the presence of SCS on the right adrenal adenoma.A laparoscopic right adrenalectomy was then performed.The histopathological examination of the resected right adrenal revealed the presence of a cortisol-producing adenoma,while CYP11B2 immunoreactivity was absent in this adenoma.However,in the adjacent nonneoplastic adrenal,multiple CYP11B2-positive adrenocortical micronodules were detected,showing the presence of aldosterone-producing adrenocortical micronodules.CONCLUSION Careful clinical and pathological examination should be performed when a patient harboring AI presents with concomitant SCS and PA.

Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing's syndrome: A case report and review of the literature

BACKGROUND Adrenocorticotropic hormone(ACTH)-independent Cushing's syndrome(CS) is mostly due to unilateral tumors, with bilateral tumors rarely reported. Its common causes include primary pigmented nodular adrenocortical disease,ACTH-independent macronodular adrenal hyperplasia, and bilateral adrenocortical adenomas(BAAs) or carcinomas. BAAs causing ACTHindependent CS are rare; up to now, fewer than 40 BAA cases have been reported. The accurate diagnosis and evaluation of BAAs are critical for determining optimal treatment options. Adrenal vein sampling(AVS) is a good way to diagnose ACTH-independent CS.CASE SUMMARY A 31-year-old woman had a typical appearance of CS. The oral glucose tolerance test showed impaired glucose tolerance and obviously increased insulin and Cpeptide levels. Her baseline serum cortisol and urine free cortisol were elevated and did not show either a circadian rhythm or suppression with dexamethasone administration. The peripheral 1-deamino-8-D-arginine-vasopressin(DDVAP)stimulation test showed a delay of the peak level, which was 1.05 times as high as the baseline level. Bilateral AVS results suggested the possibility of BAAs.Abdominal computed tomography showed bilateral adrenal adenomas with atrophic adrenal glands(right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). Magnetic resonance imaging of the pituitary gland demonstrated normal findings. A left adenomectomy by retroperitoneoscopy was performed first,followed by resection of the right-side adrenal mass 3 mo later. Biopsy results of both adenomas showed cortical tumors. Evaluations of ACTH and cortisol showed a significant decrease after left adenomectomy but could still not be suppressed, and the circadian rhythm was absent. Following bilateral adenomectomy, this patient has been administered with prednisone until now,all of her symptoms were alleviated, and she had normal blood pressure without edema in either of her lower extremities.CONCLUSION BAAs causing ACTH-independent CS are rare. AVS is of great significance for obtaining information on the functional state of BAAs before surgery.

Severe Ectopic Cushing’s Syndrome Due to ACTH-Secreting Pheochromocytoma

We report a new case of ectopic Cushing’s syndrome caused by an ACTH-producing pheochromocytoma. A 55-year-old woman presented with a history of severe proximal muscle weakness, polyuria, progressive virilization, anxiety, dyspnea on exercise, difficult to treat hypertension, and type 2 diabetes mellitus since 4 months. The laboratory data demonstrated ACTH-dependent hypercortisolism. The abdominal computed tomography scan showed a 30 mm well-defined mass in the left adrenal gland suggestive for pheochromocytoma. The adrenal veins were sampled, with intraprocedural cortisol measurement, to dosing selective ACTH and cathecolamines. The results established clearly the left adrenal gland as the source of ACTH overproduction. A left sided adrenalectomy was performed with subsequent resolution of Cushing’s syndrome. The patient was discharged in good clinical condition.

Cushing Syndrome Revealing an Adrenocortical Carcinoma

Adrenocortical carcinoma is a malignant tumor of the adrenal gland, very rare in pediatric pathology. Authors presented a pediatric case of adrenocortical carcinoma which showed neurology symptoms at 1st visit and Cushing syndrome secondarily. The patient received a ketoconazole-based treatment. The outcome was fatal before the surgical excision of the tumor, because of delayed diagnosis. Early diagnosis and multidisciplinary management of adrenocortical carcinoma could improve the prognosis in children.

Midnight Salivary Cortisol and Other Effective Factors in the Graduation of Clinical Suspect of Cushing Syndrome: Is There Any Reasonable Clinical Score?

Background: Diagnosis of Cushing’s Syndrome (CS) at the right time and with the right method is getting more important for the patients and clinicians due to high mortality rate. The most appropriate laboratory test will provide great benefits in terms of cost-effectiveness in the well-chosen group of patients. Selection of the high risk group is of crucial importance for the true diagnosis and treatment on time. Aim: The aim of this study was to evaluate the worth of the midnight salivary cortisol and to establish other effective factors in the graduation of clinical suspect of CS. Material and Methods: 115 patients were evaluated in weight, height, body mass index (BMI), waist/hip ratio, systolic, diastolic blood pressures, hirsutism, weight gain, purple-stria, plethore, buffalo-hump, supraclavicular fullness, temporal fat cushion, acnea, moonface, proximal muscle weakness, lower limb edema, ecchymosis, loss of libido, depression, diabetes mellitus, hypertension, allopecia of all patients were noted in the evaluation forms (23 findings). Patients were grouped according to clinical scores, low (16). Results: When we compare the groups in terms of midnight salivary cortisol, morning salivary cortisol after overnight dexamethasone suppression test, we found statistically significant relationship between the low and high clinical score groups, as well as between medium and high score groups (p: 0.0001). Urinary free cortisol was statistically significant only between low and high clinical score groups (p: 0.0001). Conclusion: This clinical scoring system which includes clinical signs and laboratory findings both, can be used for selection of the high risk group.

Giant adrenal tumor presenting as Cushing’s syndrome and pheochromocytoma:A case report

We report a case of a 35-year-old lady who presented with Cushingoid features and associated raised urinary metanephrine.The patient underwent open adrenelectomy.Histopathological examination revealed adreno-cortical carcinoma with microscopic lymphovascular invasion.Postoperative period was uneventful and is on follow-up for the last one year and is doing well.

Case report of Cushing＇s syndrome with an acute psychotic presentation

一位36岁的中国女性因出现狂躁、被害妄想和自杀意念3天被送至某综合医院急诊。六个月来患者易醒、过度警觉并出现躯体症状。入心身病房后,体检发现该患者满月脸、突眼,且双腿有紫纹,因此考虑急性精神症状继发于库欣综合征。血浆皮质醇、促肾上腺皮质激素(adrenocorticotropic hormone ACTH)水平升高,腹部计算机断层扫描(computed tomography,CT)发现左肾上腺肿块,证实了该诊断。使用小剂量喹硫平(75-125 mg/d)和阿普唑仑(0.4 mg/qn)来控制精神病性症状并改善其睡眠。将一个良性的非ACTH依赖性肾上腺肿瘤手术切除后,患者的皮质醇和ACTH水平恢复正常,其精神症状也在一个月内逐渐减少,此时该患者出院。患者出院后一直门诊随诊,维持喹硫平治疗(因为担心停药对睡眠和情绪稳定的影响),总时间持续1年左右,剂量从50mg渐减至25mg至减停。这时她的精神症状已经完全消失。该病例中,病人具有库欣综合征的特殊症状,因此相对容易诊断;但在库欣综合征中急性精神病性症状可能会危及生命,也可能不出现库欣综合征的典型躯体症状(如果皮质醇增多症不严重),所以临床精神科医师在鉴别难以解释的急性精神病时,应该始终考虑将库欣综合征纳入可能的鉴别诊断。

岩下窦静脉取血在ACTH依赖性Cushing综合征鉴别诊断中的应用

目的探讨岩下窦静脉取血(IPSS)在鉴别垂体和异位来源的ACTH依赖性Cushing综合征的意义.方法回顾性分析了我院2003/2005年接受此项检查的共10例ACTH依赖性Cushing综合征患者的资料.结果10例ACTH依赖性Cushing综合征的患者,通过IPSS检查仅1例患者与最后结果不符,IPSS诊断符合率90%,不符合率10%.结论岩下窦静脉取血在鉴别诊断垂体和异位ACTH依赖性Cushing综合征中有较高的准确率.因此,岩下窦静脉取血测ACTH为医生在对根据影像学检查结果无法明确诊断的患者进行治疗时可提供指导意义.

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。

ACTH非依赖性Cushing综合征的分子生物学研究进展

促肾上腺皮质激素(ACTH)非依赖性Cushing综合征包括肾上腺皮质腺瘤、肾上腺皮质癌和肾上腺皮质结节样增生,其发病机制主要与基因突变(GNAS1、PRKAR1A和PDE11A)、异位受体表达、WNT通路异常激活及抑癌基因杂合丢失等诸多因素相关,该文就上述发病机制作一综述。

Cushing综合征的临床特点与诊断分析

【目的】分析Cushing综合征各种病因的临床特征,评估诊断和病因鉴别诊断的方法和效率。【方法】回顾分析我院1996年～2006年住院经临床和病理确诊为Cushing综合征的154例病例的临床资料和实验室检查资料。【结果】85%左右的病人有典型的Cushing外貌,肾上腺腺瘤占33.8%,其中85%为育龄女性。约半数病人出现低血钾和糖尿病。血糖异常、高血压及高脂血症的发生率分别为68.7%、72.6%和67.6%。Cushing综合征诊断的敏感性从高到低依次为不被午夜1mg地塞米松抑制、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病和肾上腺腺瘤的鉴别诊断中,8mg地塞米松抑制试验的特异性和敏感性分别为86.8%和90.8%,ACTH的特异性和敏感性分别为97.2%%和65.1%。【结论】本组病例肾上腺腺瘤比例高,糖尿病发生率高。结合ACTH检测,8mg地塞米松抑制试验以及影像学检查,方可对Cushing综合征的病因进行准确的鉴别诊断。

午夜血清皮质醇水平对Cushing综合征诊断价值的初步探讨

【目的】初步探讨午夜血清皮质醇水平对Cushing综合征的诊断价值。【方法】回顾分析我院1997年12月到2007年4月收治的42例Cushing综合征患者和134例经住院检查排除Cushing综合征的肥胖症和高血压病患者,比较不同午夜血清皮质醇水平切点对Cushing综合征诊断的敏感性和特异性。【结果】以690 nmol/L(正常高限)为切点,08:00血清皮质醇水平对Cushing综合征诊断的敏感性和特异性分别为52.4%和94.0%;以08:00血清皮质醇水平的75%为切点,16:00血清皮质醇水平的敏感性和特异性分别为73.8%和72.4%;而对于24:00血清皮质醇水平,以08:00血清皮质醇水平的75%以及207、138和50 nmol/L为切点,对诊断Cushing综合征的敏感性分别为64.3%、95.2%、100.0%和100.0%,特异性分别为95.5%、93.3%、83.6%和53.0%。【结论】午夜血清皮质醇水平以207 nmol/L为切点具有较高的敏感性和特异性,对于Cushing综合征具有较高的诊断价值。

经蝶手术治疗Cushing病后的内分泌随访观察

目的探讨经蝶手术治疗Cushing病的疗效。方法回顾性分析接受经蝶手术的64例Cushing病病人的内分泌随访资料,其中10例为再次手术病人。将微腺瘤按肿瘤的直径分为2～5mm组(Ⅰ组)和6～10 mm组(Ⅱ组)。平均随访3年。结果初次手术的病人内分泌缓解率为76%,再次手术的缓解率为60%;Ⅰ组与Ⅱ组的内分泌缓解率没有统计学差异(P > 0.05)。结论经蝶手术治疗Cushing病有很好的疗效;肿瘤的体积对于缓解率没有明显的影响;初次手术失败可考虑再次行经蝶手术。

Bilateral inferior petrosal sinus sampling for the treatment of Cushing's disease Data from 52 cases from one institute over an eight-year period

The present study analyzed data from 108 Cushing＇s disease patients, who underwent transsphenoidal surgery in one hospital between January 2003 and April 2010, to investigate the performance value of bilateral inferior petrosal sinus sampling （BIPSS）. Of the 108 patients 52 underwent BIPSS prior to surgery and 56 did not. Results showed that BIPSS accuracy for the diagnosis of Cushing＇s disease was 86.5% （45/52）, and accuracy for adenoma lateralization during surgery was 76.9% （40/52）. In addition, early remission rate was significantly greater compared to patients without BIPSS. Results demonstrated that BIPSS facilitated localization and diagnosis of Cushing＇s disease and helped to predict adenoma lateralization.

生化与影像学检查对Cushing综合征的诊断价值

目的探讨各项生化与影像学检查对Ｃｕｓｈｉｎｇ综合征的诊断价值。方法对经手术和病理证实的３２例Ｃｕｓｈｉｎｇ综合征（Ｃｕｓｈｉｎｇ病所致的肾上腺皮质增生２２例，肾上腺腺瘤８例，肾上腺癌１例，异源性ＡＣＴＨ综合征１例）进行回顾性分析。结果①血皮质醇（Ｆ）单次升高者占８４．４％，昼夜节律失常率为１００％；②２４ｈ尿１７－羟皮质类固醇（１７－ＯＨ）：增生组９０．９％升高，腺瘤组８７．５％升高；③２４ｈ尿游离皮质醇（ＵＦＣ）：测定的８例患者（增生者６例，腺瘤者２例）ＵＦＣ均明显升高（１００％）；④血浆ＡＣＴＨ：测定的８例中，增生者５例升高（５／８，６２．５％），而腺瘤者２例均在正常水平以下，１例异源性ＡＣＴＨ综合征升高；⑤小剂量地塞米松抑制试验（ＤＳＴ）：增生组阳性率均为９５．５％，腺瘤组１００％；⑥大剂量ＤＳＴ：增生组阳性率分别为８１．８％和７２．７％；而腺瘤组均不被抑制（抑制率均＜５０％）；⑦Ｂ超：增生组６８．２％、腺瘤组８７．５％有阳性发现；⑧肾上腺ＣＴ：增生组９０．９％、腺瘤组１００％有阳性发现；颅脑ＣＴ：增生组中的２０例行ＣＴ检查，仅２例（１０％）垂体有阳性发现。结论血Ｆ昼夜节律失常、ＵＦＣ测定与小剂量ＤＳ?

Metabolic profile differences in ACTH-dependent and ACTH-independent Cushing syndrome

Background:The most common etiologies of Cushing’’s syndrome(CS)are adrenocorticotropic hormone(ACTH)-producing pituitary adenoma(pitCS)and primary adrenal gland disease(adrCS),both of which burden patients with metabolic disturbance.The aim of this study was to compare the metabolic features of pitCS and adrCS patients.Methods:A retrospective review including 114 patients(64 adrCS and 50 pitCS)diagnosed with CS in 2009-2019 was performed.Metabolic factors were then compared between pitCS and adrCS groups.Results:Regarding sex,females suffered both adrCs(92.2%)and pitCS(88.0%)more frequently than males.Regarding age,patients with pitCS were diagnosed at a younger age(35.40±11.94 vs.39.65±11.37 years,p=0.056)than those with adrCS,although the difference was not statistically significant.Moreover,pitCS patients had much higher ACTH levels and more serious occurrences of hypercortisolemia at all time points(8 AM,4 PM,12 AM)than that in adrCS patients.Conversely,indexes,including body weight,BMI,blood pressure,serum total cholesterol,low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),triglycerides,fasting plasma glucose,and uric acid,showed no differences between adrCS and pitCS patients.Furthermore,diabetes prevalence was higher in pitCS patients than in adrCS patients;however,there were no significant differences in hypertension or dyslipidemia prevalence between the two.Conclusions:Although adrCS and pitCS had different pathogenetic mechanisms,different severities of hypercortisolemia,and different diabetes prevalences,both etiologies had similar metabolic characteristics.

CHANGES OF CIRCADIAN RHYTHM OF GLUCOCORTICOID RECEPTOR IN PERIPHERAL LEUKOCYTES IN PATIENTS WITH CUSHING'S SYNDROME

The existence of circadian rhythm (CR) of glucocorticoid receptor (GR) in human peripheral leukocytes has been reported by us previously and it may be of physiological significance because CR of GR synchronizes with that of the reactivity of the polymorphonuclear leukocytes (PML)to cortisol (F). Since GR is regulated by glucocorticoid (GC)which also fluctuates diurnally, it remains to be answered whether CR of GR is autonomous or secondary to CR of plasma GC. It is well known that CR