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.

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.

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.

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.

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.

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.

Clinical,Biochemical,and Radiological Retrospective Analysis in Patients with Adrenal Incidentaloma-A Secondary Publication

Objective:To evaluate the epidemiological,demographic,clinical features,treatment approaches,and survival of patients followed up for adrenal incidentaloma.Methods:Data from 46 patients who were treated and followed up due to adrenal incidentaloma in the Endocrinology Department of Mersin University Health Research and Application Hospital between 2010 and 2014 were retrospectively analyzed.Results:Of the cases included in the study,13 were male,33 were female,and the mean age was 54.09±10.7 years.The most common reason for admission was abdominal pain in 34.78%of the patients,the most commonly diagnosed radiological method was dynamic adrenal CT in 60.87%,and the most common location was the left adrenal gland.The mean lesion diameter was between 26.8±16.5 mm.The frequency of hypertension was 50%,obesity 47.8%,type 2 diabetes 21.7%,osteoporosis 42.8%,and metabolic syndrome 41.3%.According to hormonal evaluation results,non-functional adrenal adenoma(NFAA)was found in 82.61%,subclinical Cushing’s syndrome(SCS)in 15.21%,and aldosteronoma in 2.1%.Myelolipoma,pheochromocytoma,and adrenocortical adenoma were diagnosed in 8 cases undergoing adrenalectomy.One patient died due to liver failure.No hormonal activation or growth in lesion size was detected during the follow-up of the patients.Conclusion:Due to the very different pathological and radiological appearances of adrenal incidentaloma,it is important to evaluate demographic,etiological,clinical,laboratory,and radiological data as a whole in the treatment and follow-up.

肾上腺意外瘤型亚临床库欣综合征患者手术前后高血糖情况及变化分析

背景 亚临床库欣综合征(SCS)是肾上腺意外瘤的常见亚型,但目前对于SCS患者高血糖与高皮质醇分泌的相关性分析及术后变化情况鲜有报道。目的 评价肾上腺意外瘤SCS患者高血糖的患病情况及其术后变化。方法 收集2010—2021年上海大学附属仁和医院(上海市宝山区仁和医院)诊治的124例患者资料并进行统计分析。对其中36例SCS患者(SCS组)、41例肾上腺腺瘤型库欣综合征患者(CSA组)及47例肾上腺无功能瘤患者(NAA组)行口服糖耐量检查(OGTT),并计算胰岛素抵抗指数(HOMA-IR)、葡萄糖曲线下面积(AUC Glu)、胰岛素曲线下面积(AUC Ins),检测患者血皮质醇、尿皮质醇、血促肾上腺皮质激素(ACTH)等激素测值,将所得结果与53例受试者(对照组)进行比较。SCS组、CSA组所有患者均经手术治疗,采用Pearson相关性分析比较SCS组、CSA组激素与糖代谢测值的相关性。结果 SCS组、CSA组、NAA组、对照组高血糖患病率分别为41.7%、51.2%、25.5%及24.5%。SCS组患者糖化血红蛋白(HbA1c)、糖负荷后2 h胰岛素(2 hPIN)、AUCGlu及AUCIns均高于对照组(P<0.05),CSA组患者空腹胰岛素(FIN)、AUCIns及HOMA-IR均高于SCS组、NAA组及对照组(P<0.05),CSA组患者HbA1c、FPG、糖负荷后2 h血糖(2 hPPG)、2 hPIN及AUCGlu均高于NAA组、对照组(P<0.05)。剔除性别、年龄影响,SCS组患者HbA1c、2 hPPG与8:00、16:00血皮质醇、尿游离皮质醇呈正相关(r=0.68,0.657,0.522,P<0.05;r=0.569,0.544,0.369,P<0.05),FPG与8:00血皮质醇呈正相关(r=0.434、P<0.05),AUCGlu与8:00、16:00血皮质醇呈正相关(r=0.397,0.409,P<0.05);CSA组患者HbA1c、FPG、2 hPPG、AUCGlu与8:00、16:00血皮质醇呈正相关(r=0.748,0.631,0.669,0.602,P<0.05;r=0.674,0.655,0.640,0.624,P<005),2 hPIN与8:00血皮质醇呈正相关(r=0.319,P<0.05)。SCS组、CSA组患者术后与术前相比,血皮质醇、尿皮质醇水平下降(P<0.05)。SCS组患者术后与术前相比,2 hPIN、AUCIns下降(P<0.05);CSA组患者术后与术前相比,FIN、2 hPIN、AUCGlu、AUCIns及HOMA-IR均下降(P<0.05)。SCS组、CSA组患者术后高血糖的患病率分为33.3%及39.0%。结论 SCS患者高血糖的患病率升高,其原因与皮质醇的高分泌有关。手术治疗后高血糖情况得以改善。

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

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.

Cushing＇s syndrome during pregnancy caused by adrenal cortical adenoma： a case report and literature review

Cushing＇s syndrome （CS） during pregnancy is a rare condition with Significant maternal and fetal complications. A case of CS during the third trimester of pregnancy secondary to adrenocortical adenoma was reported. Literature review revealed the disadvantages of different treatments in this period. Besides the conservative treatment, surgery is recommended for CS during the third trimester of pregnancy secondary to adrenal adenoma, if an experienced surgeon is available.

库欣综合征的诊疗进展

库欣综合征(CS)是一种由肾上腺皮质分泌过多糖皮质激素引起的内分泌疾病,其诊断与治疗均具挑战性。诊断过程需结合实验室和影像学检查,进行筛查、定性及定位。治疗方式以手术为主,但药物治疗同样也占据重要地位。随着对CS发病机制的深入了解,发现了更多孤儿药研发的潜在靶点。本文总结了CS的诊疗现状,并对未来的研究方向做出了展望。

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。

Pathogenesis of hepatic steatosis:The link between hypercortisolism and non-alcoholic fatty liver disease

Based on the available literature,non alcoholic fatty liver disease or generally speaking,hepatic steatosis,is more frequent among people with diabetes and obesity,and is almost universally present amongst morbidly obese diabetic patients.Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world,with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation.Previous data report that only 20%of patients with Cushing’s syndrome have hepatic steatosis.Aiming at clarifying the reasons whereby patients suffering from Cushing’s syndrome-a condition characterized by profound metabolic changes-present low prevalence of hepatic steatosis,the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome.They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing’s syndrome could result from the inhibition of the so-called low-grade chronicinflammation,mainly mediated by Interleukin 6,due to an excess of cortisol,a hormone characterized by an anti-inflammatory effect.The Cushing’s syndrome,speculatively considered as an in vivo model of the hepatic steatosis,could also help clarify the mechanisms of non alcoholic fatty liver disease.

Bilateral Macronodular Adrenal Hyperplasia

Cushing’s syndrome is the set of clinical manifestations secondary to a chronic excess of glucocorticoids. Bilateral macronodular adrenal hyperplasia with subclinical cortisol secretion is the most common, but its prevalence remains unknown. We describe a case of bilateral macronodular adrenal hyperplasia. This is a 36-year-old female patient who had been consulting for secondary amenorrhea and developing asthenia for 4 months. The clinical examination noted an overweight patient with high blood pressure, facio-trunk obesity, hirsutism and purple stretch marks in the abdomen and thighs. Biologically, hypokalemia at 2.9 meq/l (3.5 - 5.4), normal calcemia at 90 mg/l (85 - 104), fasting blood sugar was 0.84 g/l (0.7 - 1), the tests for minute, low and high dexamethasone suppression test revealed insufficient suppression of cortisol. The cortisoluria collected from the second day to the third day of the high dexamethasone suppression test was at 186 μg/24 h (<60), the ACTH (Pg/ml) was undetectable (6.4 - 49.8). The diagnosis of an independent adrenocorticotrophin (ACTH) Cushing syndrome was made and the adrenal CT scan revealed bilateral macronodular hyperplasia. A bilateral adrenalectomy was performed and a complete remission of Cushing syndrome was achieved. We prescribed to her, hydrocortisone 20 mg/day and alpha-fludrocortisone 25 to 50 μg/day, This medical observation showed that macro-nodular adrenal hyperplasia with overt Cushing syndrome can occur in the third decade of life. Bilateral adrenalectomy has resulted in a complete cure for Cushing’s syndrome, but may be fraught with complications.

Familial primary pigmented nodular adrenocortical disease without Carney complex (CNC): A case report and review of literature

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of familial Cushing's syndrome. It is characterized by bilateral adrenocortical hyperplasia with small to normal-sized adrenal glands containing multiple small adrenal cortical pigmented nodules [1,2]. PPNAD may occur in an isolated form or as familial PPNAD. Familial cases of PPNAD are usually associated with Carney complex in which Cushing’s syndrome is the most common endocrine manifestation [3]. Familial cases of PPNAD without associated Carney complex are very rare. Only a few cases of familial isolated PPNAD have been reported in the literature, mostly in females [4]. Isolated familial PPNAD has got a better prognosis than familial PPNAD associated with Carney Complex. This observation has important consequences for clinical management, follow-up and genetic counselling of such patients. Familial cases of PPNAD are rare and mostly present in females with associated Carney complex. We herein report a case of familial Cushing’s syndrome in male siblings due to PPNAD without associated Carney complex.

亚临床原发性醛固酮增多症合并亚临床库欣综合征1例并文献复习

本文报告1例罕见的亚临床原发性醛固酮增多症(subclinical primary aldosteronism,SPA)合并亚临床库欣综合征(subclinical Cushing syndrome,SCS)患者。该患者为41岁的女性,因肾上腺偶发瘤(adrenal incidentaloma,AI)入院。患者无高血压、低血钾、糖代谢异常等典型的原发性醛固酮增多症(primary aldosteronism,PA)或库欣综合征(Cushing syndrome,CS)的临床表现,实验室检查示醛固酮肾素比值(aldosterone to renin ratio,ARR)>3.7,促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)<1.6 pg/mL,最终依据术后病理学检查结果,患者被诊断为肾上腺皮质腺瘤。该病例中存在2种亚临床疾病共存的诊断,这种临床类型在目前的指南和报道中并未得到充分认识,值得关注并进行更详细的讨论。

1例妊娠合并促肾上腺皮质激素非依赖性库欣综合征患者的围手术期护理

总结1例妊娠合并促肾上腺皮质激素非依赖性库欣综合征患者行肾上腺瘤切除术围手术期的护理经验。护理要点包括妊娠高血压的管理、预防子痫;术中多学科协作管理、实施个性化手术体位安置、精准补充激素;术后做好预防肾上腺危象、个体化快速康复护理,同时给予心理护理及延续性护理。经过精心治疗和护理,患者恢复良好,术后第6天康复出院,随访6个月预后良好。

Characteristics of ectopic adrenocorticotropic hormone syndrome due to thymic carcinoid and analysis of the molecular mechanism

Ectopic adrenocorticotropic hormone （ACTH） secretion rfrom a non-pituitary tumor is a main cause of Cushing＇s syndrome, which is associated with significant morbidity and mortality. Although early studies showed that the predominant cause of ectopic Cushing＇s syndrome is small cell carcinomas of the lungs, the incidence of carcinoid, including thymic carcinoid, has increased substantially in recent surveys） This evidence suggested that the clinical syndrome of ectopic ACTH production only occurs in tumors with high proopiomelanocortin （POMC, the precursor to ACTH） transcripts generated from the start of the pituitary transcription initiation site.2

库欣综合征术后继发于亚急性甲状腺炎的甲状腺危象1例报道

患者为46岁女性,因库欣综合征5月前行肾上腺腺瘤切除术,予糖皮质激素替代逐步减量中,3周前因咽痛、饮水呛咳、恶心、呕吐自行停药。之后出现高热及意识障碍,化验提示甲状腺功能亢进,予丙硫氧嘧啶及β受体阻滞剂后意识障碍进行性加重,结合炎性指标升高、TSH受体抗体阴性及摄碘率低平考虑为亚急性甲状腺炎,加用糖皮质激素治疗后病情好转,甲亢缓解。