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.

Cushing’s溃疡12例治疗体会

目的警惕重度颅脑损伤患者上消化道出血并及早进行防治。方法监测血尿素氮胃液pH值,采取相应的预防和治疗措施。结果12例Cushing’s患者的血尿素氮水平明显高于同期无出血患者,胃液pH值均<3.0,采取防治措施后,发病率和死亡率明显降低。结论及早做出上消化道出血的预测和诊断,是降低发病率和死亡率的关键。

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.

医源性Cushing's综合征的临床诊治与护理干预

目的:分析27例滥用糖皮质激素引起的医源性Cushing’s综合征的诊断、治疗、护理。方法:对27例医源性Cush-ing’s综合征患者进行剂量递减法撤停糖皮质激素,同时治疗肾上腺皮质功能不全及肾上腺危象,对比治疗前后临床症状,包括全身症状、向心性肥胖、满月脸、痤疮、水肿,以及治疗前后代谢指标,包括血钾、平均血糖、胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白水平的变化。结果:(1)治疗后全身症状、向心性肥胖、满月脸、痤疮、水肿均较治疗前改善(P<0.05);(2)治疗后血钾、平均血糖、CHO、TG、LDL均较治疗前降低(P<0.05);治疗后HDL较治疗前升高(P<0.05)。结论:临床工作需合理应用糖皮质激素,严格掌握其适应证与禁忌证,使其副作用和并发症的发生降到最低水平。

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.

Cushing's reflex in a rare case of adult medulloblastoma

BACKGROUND: Medulloblastoma is a primitive neuro-ectodermal tumor. It is common in childhood, but rarely seen at adult age, comprising only 1% of primary brain tumors.METHODS: We treated a 31-year-old man presented to the emergency department(ED) with a chief complaint of nausea and vomiting for one week duration. Immediate frozen section revealed a grade IV medulloblastoma. During the hospital course, the patient was given craniospinal irradiation with chemotherapy.RESULTS: The patient was eventually discharged from the hospital to an assisted living facility after an uneventful 15-day course with the aid of social work.CONCLUSIONS: Despite intracranial tumors generally being slow growing masses, this patient demonstrates how quickly one can decompensate, and how important it is to recognize these clinical signs and symptoms of an intracranial lesion. Although these symptoms(i.e. Cushing response) are extremely rare, the ED physician should be aware and appreciate their clinical signifi cance.

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.

Role of adrenalectomy in treating recurrent Cushing's disease:A report of 43 cases

Objective To evaluate the efficacy of laparoscopic adrenalectomy and open adrenalectomy in treating recurrent Cushing ’s disease. Methods Forty-three patients ( 29 females and 14 males) with recurrent Cushing’s disease treated with laparoscopic adrenalectomy ( LA,n = 32) or open ( OA,n = 11) adrenalectomy from 2000

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.

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

Pituitary-dependent hyperadrenocorticism in a terrier dog:A case report

We report a case of pituitary-dependent hyperadrenocorticism in a 10-year-old,female,terrier dog.The animal was admitted due to polyphagia,weight gain,polyuria,polydipsia,hair loss,exercise intolerance and panting at rest.On physical examination,abdominal distention,truncal and bilaterally symmetric alopecia,thin hypotonic skin,comedones,bruising,hyperpigmentation and calcinosis cutis on the dorsal midline were observed.Hematologic investigations showed stress leukogram,high serum alkaline phosphatase activity,mild to moderate alanine aminotransferase activity,hypercholesterolemia,hypertriglyceridemia and hyperglycemia.Mild generalized interstitial lung patterns and hepatomegaly were detected in the radiographs.Bilaterally symmetric normal-sized adrenal glands were also diagnosed in ultrasonography.Diagnosis of pituitary-dependent hyperadrenocorticism was confirmed with low-dose dexamethasone suppression test.The dog was successfully treated with mitotane.

垂体细胞增生的诊断和治疗

目的探讨垂体细胞增生的诊断与治疗。方法男性2例,女性42例,平均年龄28.7岁,平均病程2.4年。临床表现和内分泌检查符合闭经泌乳综合征13例,库欣综合征11例,巨人症1例,无内分泌功能紊乱19例。蝶鞍MRI正常3例,垂体上缘膨隆30例,蝶鞍内信号不均匀26例,垂体柄偏斜17例。44例均行经口鼻蝶窦显微外科垂体探查术。结果44例术后病理均为垂体前叶细胞增生,随访3个月至5年。闭经泌乳患者术后改善12例,复发1例。库欣综合征患者术后改善8例,稳定1例,复发2例。巨人症患者术后无改善。无内分泌功能紊乱症状患者术后改善14例。结论垂体细胞增生在术前很难明确诊断,手术疗效较垂体腺瘤差,易复发。

库欣病的诊断与治疗

库欣病是指由于垂体促肾上腺皮质激素（adrenocorticotropichormone,ACTH）腺瘤或ACTH细胞增生,使ACTH分泌异常增多,从而导致机体内血皮质醇升高而引起的病理、生理等一系列代谢紊乱综合征.库欣病的诊治较为复杂,涉及临床、实验室、影像学等诸多学科,故需多科医师协同.治疗首选内镜下经蝶窦垂体瘤切除,但可能仍需结合放疗、药物等综合治疗,才能达到更好的疗效,并需要长期的随访以判断预后及复发等情况.本文将对库欣病的诊治予以综述,以期有助于临床工作.