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.

甲磺酸阿帕替尼靶向治疗转移性去势抵抗性前列腺癌的临床疗效观察

目的:评价甲磺酸阿帕替尼单药靶向治疗常规治疗失败的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)的近期疗效和不良反应。方法:收集天津医科大学第二医院2016年6月至2017年12月收治的25例常规治疗失败的mCRPC患者临床资料,观察口服甲磺酸阿帕替尼后的影像学检查,根据最新修订的实体瘤疗效评价标准(m-RECIST)、癌痛评分和前列腺特异性抗原(prostate specific antigen,PSA)的变化,回顾性分析阿帕替尼靶向治疗4个疗程(平均约112 d)后患者的近期疗效,并对靶向治疗后出现的不良反应进行初步分析。结果:25例患者平均发病年龄72(53~81)岁,病理类型均为腺癌,除3例失访,无完全缓解(complete response,CR),部分缓解(povtial response,PR)11例(44%),疾病稳定(stable disease,SD)8例(32%),疾病进展(progresive disease,PD)3例(12%)。客观缓解率(objective remission rate,ORR)为44%,疾病控制率(disease control rate,DCR)为76%。25例患者治疗中出现一系列不良反应,其中乏力22例(88%)、胃肠道反应15例(60%),血压升高7例(28%),手足综合征6例(24%),头晕不适、蛋白尿等其他不良反应,经对症处理后好转。结论:甲磺酸阿帕替尼治疗常规治疗失败的mCRPC近期疗效满意,治疗过程中不良反应的发生率较高,但多为轻中度反应,需要积极对症处理。今后仍需进一步探索该药治疗mCRPC的机制,为更多患者寻求更为有效的治疗策略。

Evaluating Tislelizumab, Lenvatinib, and FOLFOX4-HAIC as a Conversion Therapy for Unresectable Hepatocellular Carcinoma

Background and aims:Conversion therapy downstages tumors and renders patients with unresectable hepatocel-lular carcinoma(HCC)eligible for radical resection.This study aimed to evaluate the efficacy and safety of tislelizumab plus lenvatinib and hepatic artery infusion chemotherapy with oxaliplatin,fluorouracil,and leuco-vorin(FOLFOX4-HAIC)as a first-line conversion therapy.Methods:Clinical data from HCC patients who were treated with the triple therapy between April 2021 and April 2022 were retrospectively analyzed.The primary outcome included objective response rate(ORR),disease control rate(DCR),conversion resection rate(CRR),and treatment-related adverse events(TRAEs).Results:A total of 18 patients completed conversion therapy assessment,which ended on March 27,2023.The patients had a median age of 55.5(37–72)years,and 94.4%were male.According to mRECIST,tumor shrinkage was observed in all patients,with an ORR of 94.4%(17/18),a DCR of 94.4%(17/18),and a median time to response of 1.4(0.7–3.0)months.Successful conversion was observed in 61.1%(11/18)of patients(mRECIST).The CRR and pathological complete response were 38.9%(7/18)and 57.1%(4/7),respectively.The median progression-free survival(PFS)was 17.8 months,while median overall survival was not reached.The 6-and 9-month PFS rates were 83.3%and 66.7%,respectively.The most common TRAE(16/18 patients,88.9%)was an increase in aspartate aminotransferase levels.Conclusion:Tislelizumab combined with lenvatinib and FOLFOX4-HAIC achieved a high conversion rate and acceptable toxicity in patients with unresectable HCC,suggesting that this combination may represent a new conversion strategy for this population.

Influence of HbA1c on short-term blood pressure variability in type 2 diabetic patients with diabetic nephropathy

The aim of this study was to understand the characteristics of blood pressure （BP） variability in subjects with diabetic nephropathy （DN）, and identify the probable predictors affecting BP variability. Fifty-one chronic kidney disease （CKD）-hypertensive patients without diabetes （NDN group） and sixty type 2 diabetic patients with overt DN （DN group） were enrolled in this study. The values of short-term BP variability were obtained from 24 h ambulatory BP monitoring （ABPM）. Variance analysis or nonparametric analysis revealed that 24-h systolic BP variability and night- time systolic BP variability of the DN group were significantly higher than those of the NDN group [（12.23±3.66） vs. （10.74±3.83） mmHg, P〈0.05; （11.23±4.82） vs. （9.48±3.69） mmHg, P〈0.05]. Then the patients of the DN group were divided into two groups according to glycated hemoglobin （HbAlc） level： Group A （HbA1c〈7%） and Group B （HbA1c〉7%）, and the t-test showed that patients in Group B had larger 24-h diastolic, daytime diastolic, and nighttime systolic/diastolic BP variability compared with Group A. In the DN group, partial correlation analysis revealed that HbAlc exhibited a strong association with 24-h diastolic, daytime diastolic, nighttime systolic and diastolic BP vari- ability （P〈0.001, P〈0.001, P〈0.05, and P〈0.001, respectively）. Taken together, larger short-term BP variability was detected in hypertensive type 2 diabetic patients with overt nephropathy and renal insufficiency. It may imply that the optimal BP variability level could benefit from a better glycaemic control.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

Background： Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism （IHH） may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone （ACTH） and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal （HPA） axis in patients with and without nonalcoholic fatty liver disease （NAFLD）, and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. Methods： This was a retrospective case-control study involving 75 Chinese male IHH patients （mean age 21.4 ± 3.8 years, range 17 30 years） and 135 healthy controls after matching tbr gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone. ACTH, and cortisol and biochemical tests. Results： Higher basal serum ACTH levels （8.25 ±3.78 pmol/L vs. 6.97 ±2.81 pmol/L） and lower cortisol levels （366.70 ±142.48 nmol/L vs. 452.82 ± 141.53 nmol/L） were observed ill male IHH patients than healthy subjects （all P 〈 0.05）. IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD （34.9% vs. 4.4%） than the controls （all P 〈 0.05）. Basal serum ACTH （9.91 ±4.98 pmol/L vs. 7.60 ±2.96 pmol/L） and dehydroepiandrosterone sulfate （2123.7 ±925.8 μg/L vs. 1417.1 ±498.4 μg/L） levels were significantly higher in IHH patients with NAFLD than those without NAFLD （all P 〈 0.05）. We also found that basal serum ACTH levels were positively correlated with NAFLD （r = 0.289, P 〈 0.05） and triglyceride levels （r - 0.268, P 〈 0.05） in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. Conclusions： The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Association between sleep duration and incidence of type 2 diabetes in China: the REACTION study

Backgrounds: Inadequate sleep duration is associated with a higher risk of type 2 diabetes and the relationship is nonlinear. We aim to assess the curve relationship between night sleep duration and the incidence of type 2 diabetes in China.Methods: A cohort of 11,539 participants from the REACTION study without diabetes at baseline (2011) were followed until 2014 for the development of type 2 diabetes. The average number of hours of sleep per night was grouped. Incidence rates and odds ratios (ORs) were calculated for the development of diabetes in each sleep duration category.Results: Compared to people who sleep for 7 to 8 h/night, people with longer sleep duration (≥9 h/night) had a greater risk of type 2 diabetes (OR: 1.27;95% CI: 1.01-1.61), while shorter sleep (<6 h/night) had no significant difference in risk of type 2 diabetes. When the dataset was stratified based on selected covariates, the association between type 2 diabetes and long sleep duration became more evident among individuals <65 years of age, male, body mass index <24 kg/m2 or with hypertension or hyperlipidemia, no interaction effects were observed. Furthermore, compared to people persistently sleeping 7 to 9 h/night, those who persistently slept ≥9 h/night had a higher risk of type 2 diabetes. The optimal sleep duration was 6.3 to 7.5 h/night.Conclusions: Short or long sleep duration was associated with a higher risk of type 2 diabetes. Persistently long sleep duration increased the risk.

Spontaneous retroperitoneal hemorrhage after hemodialysis involving anticoagulant agents

In this paper, we described the symptoms and treatment of a patient with diabetic nephropathy accom- panied by spontaneous retroperitoneal hemorrhage after hemodialysis. An elderly female patient with diabetic neph- ropathy presented with severe pain, numbness, and an increasing swelling in the left hip and left thigh after six ses- sions of hemodialysis involving the use of an antiplatelet drug and an anticoagulant agent. Her hemoglobin decreased to 46 g/L. An abdominal ultrasound showed a hematoma in the left retroperitoneal space, and computed tomography (CT) findings revealed a 6 cm×8 cm×10 cm hematoma in the left psoas muscle. After aggressive supportive therapy [the administration of packed red blood cell transfusion, carbazochrome sodium sulfonate injection, and continuous venovenous hemofiltration (CVVH)], the patient's vital signs stabilized and her hemoglobin increased to 86 g/L. Repeat CT showed that the hematoma had been partially absorbed after two weeks. Eventually, the patient was discharged with stable vital signs. Physicians should be aware of the possibility of spontaneous retroperitoneal hemorrhage, particularly in patients with diabetic nephropathy undergoing hemodialysis involving the use of anticoagulant agents.

Spontaneous retroperitoneal hemorrhage after hemodialysis involving anticoagulant agents

In this paper,we described the symptoms and treatment of a patient with diabetic nephropathy accompanied by spontaneous retroperitoneal hemorrhage after hemodialysis.An elderly female patient with diabetic nephropathy presented with severe pain,numbness,and an increasing swelling in the left hip and left thigh after six sessions of hemodialysis involving the use of an antiplatelet drug and an anticoagulant agent.Her hemoglobin decreased to 46 g/L.An abdominal ultrasound showed a hematoma in the left retroperitoneal space,and computed tomography(CT) findings revealed a 6 cm×8 cm×10 cm hematoma in the left psoas muscle.After aggressive supportive therapy [the administration of packed red blood cell transfusion,carbazochrome sodium sulfonate injection,and continuous venovenous hemofiltration(CVVH)],the patient's vital signs stabilized and her hemoglobin increased to 86 g/L.Repeat CT showed that the hematoma had been partially absorbed after two weeks.Eventually,the patient was discharged with stable vital signs.Physicians should be aware of the possibility of spontaneous retroperitoneal hemorrhage,particularly in patients with diabetic nephropathy undergoing hemodialysis involving the use of anticoagulant agents.

腹腔镜脾切除联合贲门周围血管离断术中转开腹风险预测模型的构建

目的建立腹腔镜下脾切除联合贲门周围血管离断手术(LSED)中转开腹的风险预测模型。方法回顾性分析2011年2月至2020年11月空军军医大学第二附属医院普外科收治的358例肝硬化门静脉高压患者的临床资料,所有患者均首先尝试LSED。采用单变量Logistic和最小化绝对收缩和选择算子(LASSO)回归分析中转开腹的独立危险因素,并用R语言构建中转开腹列线图预测模型。比较腹腔镜组和中转开腹组患者术中及术后情况。结果358例患者中31例中转开腹,中转开腹率为8.7%。单因素分析中,终末期肝病模型(MELD)评分高、BMI≥24 kg/m2、有上腹部手术史、食管胃底静脉曲张红色征、PLT计数低及凝血酶原时间延长均是发生中转开腹的危险因素(均P<0.05)。LASSO回归最终确定5个因素:MELD评分、BMI、PLT、上腹部手术史及食管胃底静脉曲张红色征。成功构建列线图预测模型,模型的ROC曲线下面积为0.831。相比于腹腔镜组,中转开腹组手术时间延长、出血量增加、术后腹腔引流时间和住院时间均延长、围手术期并发症的发生率高,差异均有统计学意义(t=-2.167,P=0.031;Z=-4.350,P<0.01;Z=-3.102,P=0.002;Z=-3.454,P=0.001;χ^(2)=8.773,P=0.003)。结论采用LASSO回归筛选出5个对中转开腹影响最大的指标,即MELD评分、BMI、PLT计数、食管胃底静脉曲张红色征及既往上腹部手术史,据此建立的列线图预测模型具有良好的预测能力。中转开腹的患者有更差的短期预后。