Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Histological Study on the Adrenal Gland of Zebra

In order to explore the histological structure of zebra and to protect en- dangered species diversity, it is especially important to study the zebra adrenal his- tological structure. 2 zebra adrenals were studied by means of histological methods. The adrenal gland tissues were dissected into serial paraffin sections at the thick- ness of 3 μm. After HE and Masson staining, they were observed and photographed by the light microscope and Image-Pro Plus 6.0. The results show that zebra adrenal capsule is covered with thick connective tissue, which is about 230 μm. A large number of nerves and blood vessels are distributed in the capsule. The area of cortex is about 5 times larger than medullae. Zona glomerulosa is thin, about 300？m. The cells were arranged as column and ball. Zona fasciculata with the thickness of 1 750 μm is 6 times as thick as zona glomerulosa. The cells were ar- ranged in cord. Zona reticular with the thickness of 250 wm was closely adjacent to medulla and formed a jagged boundary. The medulla with the area of 4 mm2 was deeply dyed. It was concluded that some sympathetic ganglion cells were found in the medulla arranged in groups and surrounded with zona reticular cells but lots of the cells were found in zona reticular. Some connective tissue with chromaffin cells was found in the medulla center vein. The purpose of the present study provides reliable evidences for further study on morphology, physiology and pathology of the zebra.

Expression of Angiotensin Ⅱ Receptors in Aldosterone-producing Adenoma of the Adrenal Gland and Their Clinical Significance

The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT1R and AT2R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT1R and AT2R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry. The expression of AT1R in adenoma, tissues adjacent to tumor, and normal tissues of the adrenal gland showed no significant differences. The expression of AT2R in APA tissue was lower than that in normal adrenal gland tissues (P<0.05). Correlation analysis of the mRNA expression level of AT2R and clinical data from patients demonstrated that AT2R expression was negatively related to plasma aldosterone concentration (PAC) (r=-0.467, P<0.05), but positively related with plasma renin activity (PRA) (r=0.604, P<0.05). It is concluded that down-regulation of the AT2R expression is possibly related with the tumorigenesis of APA.

Evaluation of Normal Adrenal Gland Volume by 64-slice CT

Objective To measure volume and other parameters of normal adrenal glands in Chinese adults with 64-slice multidetector CT, to evaluate the relationship of volume result with age, sex and body size, and to explore the correlations between adrenal volume and other measurements. Methods This study was based on 125 acquired contrast-enhanced upper abdominal CT scans performed with a 64-slice CT. The final study group consisted of 81 patients (49 males, 32 females). Portal venous phase images were studied for the measurements. Both the reconstruction interval and thickness were 1.5 mm. Each adrenal gland was outlined manually with computer-assistant technology to calculate its volume. The maximal sectional area, length, width and thickness of each adrenal gland were also measured. Results The mean age of total population was 47.9±13.0 (range: 20-76) years. The left, right, and total adrenal gland volumes were 4.23±0.74 (range: 2.85-5.83) cm 3 , 4.26±0.86 (2.59-6.56) cm 3 , and 8.50±1.40 (5.80-11.39) cm 3 , respectively. These volumes increased with weight (r=0.381, 0.389, and 0.437 respectively, all P<0.001), height (r=0.386, P<0.001; r=0.297, P=0.007; r=0.384, P<0.001) and body surface area (r=0.406, 0.392, and 0.452, all P<0.001). There was no significant difference in left, right or total adrenal volume with regard to sex after applying General Linear Model procedure to reduce the impact of weight (F=1.304, 0.064, and 0.597, all P>0.05), nor did volume change significantly with age (r=-0.033, -0.014, and -0.026, all P>0.05). Nearly all descriptors of bilateral adrenal glands correlated with ipsilateral volume except thickness (r=-0.027, P=0.814) and width (r=0.166, P=0.138) in the left side. Among these parameters, length had a stronger correlation with volume than others in the both left (r=0.412, P<0.001) and right (r=0.516, P<0.001) adrenal glands. Conclusion Our study has defined the volume distribution and other parameters of normal adrenal glands in Chinese adults, which provide a baseline for future studies.

Role of endoscopic ultrasound fine-needle aspiration evaluating adrenal gland enlargement or mass

AIM： To report the clinical impact of adrenal endoscop-ic ultrasound fine-needle aspiration （EUS-FNA） in the evaluation of patients with adrenal gland enlargement or mass.METHODS： In a retrospective single-center case-series, patients undergoing EUS-FNA of either adrenal gland from 1997-2011 in our tertiary care center were included. Medical records were reviewed and results of EUS, cytology, adrenal size change on follow-up imag-ing ≥ 6 mo after EUS and any repeat EUS or surgery were abstracted. A lesion was considered benign if： （1） EUS-FNA cytology was benign and the lesion remained 〈 1 cm from its original size on follow-up computed tomography （CT）, magnetic resonance imaging or repeat EUS ≥ 6 mo after EUS-FNA; or （2） subsequent adrenalectomy and surgical pathology was benign. RESULTS： Ninety-four patients had left （n = 90） and/or right （n = 5） adrenal EUS-FNA without adverse events. EUS indications included： cancer staging or suspected recurrence （n = 31）, pancreatic （n = 20）, medi-astinal （n = 10）, adrenal （n = 7）, lung （n = 7） mass or other indication （n = 19）. Diagnoses after adrenal EUS-FNA included metastatic lung （n = 10）, esophageal （n= 5）, colon （n = 2）, or other cancer （n = 8）; benign primary adrenal mass or benign tissue （n = 60）; or was non-diagnostic （n = 9）. Available follow-up confrmed a benign lesion in 5/9 non-diagnostic aspirates and 32/60 benign aspirates. Four of the 60 benign aspirates were later confrmed as malignant by repeat biopsy, follow-up CT, or adrenalectomy. Adrenal EUS-FNA diagnosed metastatic cancer in 24, and ruled out metastasis in 10 patients. For the diagnosis of malignancy, EUS-FNA of either adrenal had sensitivity, specifcity, positive predic-tive value and negative predictive value of 86%, 97%, 96% and 89%, respectively.CONCLUSION： Adrenal gland EUS-FNA is safe, mini-mally invasive and a sensitive technique with signifcant impact in the management of adrenal gland mass or enlargement.

Incidentally detected hydatid cyst of the adrenal gland:A case report

Hydatid cysts are a zoonotic disease that can involve many organs and tissues in the human body but primarily involve the liver and lungs. Of the main organs, adrenal glands are those seldom affected by hydatid cysts. The purpose of this study was to present a case with an incidentally detected hydatid cyst of the right adrenal gland on computed tomography, and a positive echincoccus Ig G enzyme-linked immunosorbent assay test on top of a toxic multinodular thyroid goiter for which thyroidectomy was indicated.

Establishment of rat model of combined kidney-adrenal gland allotransplantation

Objective： To establish a rat model of combined kidney-adrenal gland and allotransplantation, and to explore the immunoprotecive effect of the transplanted adrenal gland on the transplanted kidney in the combined transplantation. Methods. SD rats 160 served as donors and recipients. The combined kidney-adrenal gland allotransplantation was performed. Infusion was conducted and prepared at prime position ,and the kidney and adrenal gland were at the left side. Direct vascular anastomosis and operation of connecting ureter attached part of bladder with the bladder were conducted. The kidney pedicle of the right side was ligated. Results： A stable and mature rat model of combined transplantation was established. The warm ischemia time was 30 seconds, and the cold ischemia time was 90-120min.The average time was 100 min. The operation time was 150 min. The survival time of the recipients was 21 days. The successful rate of the operation was 75%. Conclusion： The model of the combined kidney-adrenal gland allotransplantation can be established with higher successful rate. The model can be used to explore that transplanted adrenal gland may have immunoprotecive effect on the transplanted kidney in the combined transplantation.

Ovarian thecal metaplasia of the adrenal gland in association with Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome(BWS) is an overgrowth syndrome associated with increased risk to develop malignancies including adrenocortical carcinoma. Ovarian thecal metaplasia of the adrenal gland is a rare tumorlike mesenchymal lesion in BWS patients that lacks detailed radiological description. We report a 17-yearold female patient with BWS, associated with bilateral Wilms tumor, hepatic hemangiomatosis, pancreatic neuroendocrine tumor, and a phyllodes tumor of the right breast. Surveillance abdominal ultrasound identified a right adrenal mass that was further characterized by computed tomography and magnetic resonance imaging. Radiologically, this mass displayed features that overlap with adrenocortical carcinoma and pheochromocytoma but after pathological examination this proved to be an ovarian thecal metaplasia of the adrenal gland. Adrenal masses in BWS should raise the suspicion for adrenocortical carcinoma though other adrenal tumors including ovarian thecal metaplasia can be seen in these patients.

Ultrasonographic Changes of Adrenal Glands Size under Trilostane Therapy, Their Correlation with Clinical Signs and Endocrine Tests and Possibility of Introducing Ultrasound as Additional Monitoring Modality of Cushing’s Syndrome

A prospective study of 15 dogs with diagnosed Cushing’s syndrome was made to find a correlation between adrenal size enlargement, clinical signs and results of an ACTH stimulation test. To our knowledge, no study was made trying to correlate changes in adrenal size, response to therapy and ACTH stimulation test results. Ultrasonographic evaluation and an endocrine test (ACTH stimulation test/“pre pill”) were performed in each dog two weeks after initiating the therapy, two to four weeks after changing the dosage of trilostane and ideally 10 weeks after establishing the right dosage of trilostane (two owners showed up later on date due pandemic of COVID-19). The results indicate that there is correlation between adrenal size enlargement and response to trilostane therapy. In this study, all dogs that had increase in adrenal gland size of more than 7% showed as well clinical improvement of HAC (hyperadrenocorticism) signs under trilostane therapy. Further, possible multicentric, studies should be performed to verify assumed correlation between adrenal size enlargement and positive response to trilostane therapy.

A Case Report of Two Primary Cancers, Breast Cancer with Adrenal Gland Metastatic and Second Primary Neuroendocrine Tumor in Colon, a Rare Case in Al-Bashir Hospital

A 68 years old female, was diagnosed as a case of right breast cancer in 2013;grade II/III according to Bloom Richardson grading, Modify radical mastectomy (MRM) was done and the pathology report showed moderately differentiated invasive ductal carcinoma (IDC), stage T3N3M0. Immunohisrochemisty (IHC) findings revealed a tumor with Triple positive. Patient refused to treat by chemotherapy. Patient was given adjuvant trastuzumab (first dose 8 mg/kg, followed by 6 mg/kg every three weeks) for the period of one year (16) cycles after which she went on regular follow up. Exemestane tab for 5 years and radiotherapy (50 gray in 25 fractions) was applying on right breast. One year and half after diagnosed primary breast cancer, patient complained from severe diarrhea 8 times per day watery contents, vomiting and suffered from lower abdominal pain. PET scan for whole body in October 2014 was done;the results showed ascending colon is highly suspicious for malignancy and moderately hypermetabolic left adrenal mass. Subtotal colectomy surgery was done, the pathology report of biopsy revealed low grade malignant neuroendocrine neoplastic lesion stage of T3N1Mo. Physician prescribed octreotide acetate 20 mg I. M monthly due to neuroendocrine lesion. In January 2016, cancer recurrence in the same right breast, IHC revealed ER+, PR&minus;, Her 2+, physician decided to change exemestane to fulvestrant 250 mg s. c for 6 cycles. Radiation therapy was applied 20 gray in 10 fractions on scar. In May 2016, CAP-CT scan result revealed two enlarged left axillary L.N and left soft tissue density adrenal mass (3.0 × 2.3). Excisional lymph node was done which revealed IDC, ER+, PR&minus;, Her 2+. Physician decided to discontinue fulvestrant and switch to exemestane 20 mg monthly. CAP-CT was done in Feb 2017;single left axillary L.N 1 cm, small hypodense lesion (spleen 4 cm), left adrenal lesion (2.2 × 2.6 cm) and osteolytic lesion were noted in iliac areas, so the physician considered those results a metastatic area from breast and prescribed lapatinib 84 tablets. Patient now onoctreotide acetate 20 mg I. M, trastuzumab 440 m, exemestane and lapatinib tablets) monthly, zoledronic acid 4 mg q 3 months, patient now still on follow up with a good condition. Conclusion: Breast cancer metastatic to left adrenal gland which is extremely rare especially when they originate from IDCs. The present case is the seventh breast cancer metastatic to the adrenal gland in the literature up to our search. Neuroendocrine tumor was happened in colon after one year and half which was a rare second primary malignancy (SPM) among female breast cancer.

成人肾上腺术中超声表现

目的 观察成人肾上腺术中超声(IOUS)表现。方法 收集71例因肝脏、胆道或胰腺病变而接受外科手术治疗患者,观察肾上腺IOUS表现,并与CT/MRI双侧肾上腺显示率和厚度测值进行比较。结果 成人肾上腺IOUS表现为边界清晰、形态不规则的双侧弱回声结构。CT/MRI肾上腺显示率为97.18%(138/142)。IOUS肾上腺显示率为95.07%(135/142),右侧92.96%(66/71)、左侧97.18%(69/71),且可见4侧CT/MRI未能显示的肾上腺;IOUS所测肾上腺厚度均大于CT/MRI(P均<0.05)。结论 IOUS中,成人肾上腺表现为边界清晰、形态不规则的双侧弱回声,左侧显示率高于右侧。

新生儿肾上腺囊性神经母细胞瘤临床及CT表现

目的观察新生儿肾上腺囊性神经母细胞瘤(CNB)的临床及CT表现。方法回顾性分析经手术病理确诊的8例新生儿肾上腺CNB,记录其临床资料,观察术前全腹CT平扫及增强表现。结果8例中,6例(6/8,75.00%)于胎儿期、2例(2/8,25.00%)于新生儿期经超声检出;均见单侧肾上腺单发病灶,位于左、右侧肾上腺各4个(4/8,50.00%),最大径2.3~6.1 cm、中位最大径4.5 cm。CT显示8个(8/8,100%)病灶均表现为局限性厚壁囊性肿块,其中3个(3/8,37.50%)囊内密度均匀、3个(3/8,37.50%)囊内有分隔、1个(1/8,12.50%)囊内见少许漂浮物、1个(1/8,12.50%)囊内同时存在分隔及漂浮物,均未见钙化;病灶均未见跨越中线、均无血管包绕,7个(7/8,87.50%)边界清晰、1个(1/8,12.50%)边界欠清,均轻度推压周围结构;增强后囊壁及分隔轻度强化。2例累及肝脏。结论新生儿肾上腺CNB多于胎儿期检出,CT主要表现为厚壁囊性肿块,边界清晰,内可有分隔及漂浮物,增强后囊壁及分隔轻度强化;可出现肝脏转移。

基于CT影像的人工智能在肾上腺良性肿瘤中的应用进展

CT是诊断肾上腺良性肿瘤的重要手段,但仍有少部分肾上腺良性肿瘤难以确诊。人工智能(AI)可以运用计算机算法模仿人脑且具有学习和解决问题等任务的能力,包括机器学习和深度学习,已广泛应用于肾上腺良性肿瘤的诊断、鉴别诊断及治疗。就目前基于CT影像的人工智能在肾上腺良性肿瘤中的应用进展进行综述。

加速康复外科在肾上腺肿瘤微创手术中的应用研究

目的探讨加速康复外科(ERAS)应用于肾上腺肿瘤微创手术中的可行性和有效性。方法选择接受后腹腔镜肾上腺肿瘤切除术的患者139例,肿瘤最大径≤6.0 cm。根据围手术期方案分为ERAS组65例和常规组74例。比较2组患者一般资料(年龄、性别、肿瘤位置、肿瘤直径),手术指标(手术时间、手术出血量),术后康复指标(首次下床时间、首次排气时间、术后导尿管留置时间、术后引流管留置时间、术后住院时间)以及并发症的发生情况。结果2组患者性别、年龄、肿瘤位置、肿瘤直径、手术时间和手术出血量比较差异均无统计学意义(P>0.05)。ERAS组患者首次下床时间、首次排气时间、导尿管留置时间、引流管留置时间和住院时间均短于常规组,且术后并发症总发生率低于常规组(P<0.05)。结论ERAS方案应用于肿瘤最大径≤6.0 cm的肾上腺肿瘤患者微创手术中是安全可行的。

深度学习重建算法对肾上腺肿瘤的检出及鉴别效能的影响

目的:探讨不同等级深度学习图像重建(DLIR)算法对肾上腺肿瘤的检出、组学特征可重复性和组学模型鉴别肿瘤类型效能的影响。方法:回顾性收集41例肾上腺功能性腺瘤(FAA)和46例肾上腺转移瘤(AM)患者的临床和影像资料。CT增强扫描完成后,对静脉期的原始数据采用4种强度等级(DL1、DL2、DL3、DL4)的DLIR算法进行重建。首先采用主、客观指标比较4种等级间图像质量的差异;然后使用Research Portal V1.1科研平台对各组重建图像上肾上腺肿瘤进行分割并提取450个影像组学特征,包括原始图像特征90个和拉普拉斯(LoG)滤波后的高阶特征(高斯核:0.5、1.0、1.5、2.0)360个。采用一致性相关系数(CCC)评估采用不同图像重建等级测量的FAA和AM组学特征的可重复性。最后,在各组重建图像中采用逐步特征选择策略,筛选出最优特征集并构建鉴别FAA和AM的组学模型。利用五折交叉验证法验证4个组学模型的鉴别效能,利用分层交叉验证法测评4个模型的泛化能力。结果:DL2和DL3在肾显示上腺肿瘤的清晰度方面最优,得分为4(4,5),优于DL1相应得分4(3,5)和DL4相应得分4(3,4),且差异具有统计学意义(F=139.045,P<0.05)。随着DLIR降噪等级的提升,原始特征CCC值>0.85的个数逐渐减少,DL4中FAA和AM特征可重复的比例仅占39.3%(21/90)和50.9%(29/90)。组学特征经过LoG滤波(高斯核2.0)处理后,CCC值>0.85的个数增加,DL4中FAA和AM特征可重复的比例占91.1%(82/90)和93.3%(84/90)。4个组学模型在测试集中的曲线下面积(AUC)和符合率均>0.75,DeLong检验显示AUC的差异无统计学意义(Z=0.177~1.284,P=0.199~0.859)。但分层交叉验证显示,DL4重建图像的泛化能力最弱,AUC和符合率均<0.75。结论:高降噪等级的DLIR算法会降低对肾上腺肿瘤显示的清晰度以及组学模型的泛化性。虽然LoG滤波器(高斯核:2.0)有助于提升组学特征测量的可重复性,但仍建议在肾上腺影像诊断和组学模型训练时,使用中低降噪等级的DLIR图像。

原发性色素性结节状肾上腺皮质病临床病理分析及文献复习

目的探讨原发性色素性结节状肾上腺皮质病(PPNAD)的临床病理学特征。方法收集首都医科大学附属北京安贞医院2009年1月至2023年6月2例原发性色素性结节状肾上腺皮质病患者的临床资料、影像学检查、病理特征,进行HE染色及免疫组织化学染色,分析其组织形态及免疫组织化学表达特征,并进行相关文献复习。结果例1男,31岁,肿瘤发生在右侧肾上腺。例2女,63岁,肿瘤发生在左侧肾上腺。镜下观察肾上腺皮质均呈多结节状增生,增生的结节主要由较大的颗粒状嗜酸性粒细胞构成,胞质内含不等量脂褐素。免疫表型:Syn、CD56、α-Inhibin、SDHB呈阳性表达,NSE、CK部分呈阳性表达,CgA、S-100、EMA呈阴性表达,Ki-67增殖指数约为2%;病理诊断为原发性色素性结节状肾上腺皮质病。结论原发性色素性结节状肾上腺皮质病较为罕见,诊断时需综合影像学、组织病理学及免疫组织化学染色进行诊断,必要时辅助基因检测以明确诊断。

The Diagnosis and Treatment of Virilizing and Fem- inizing Adrenal Syndrome

Objective: To inquire into diagnosis, and treatment of virilizing andfeminizing a-drenal syndrome, differential diagnosis between benign and malignant sex hormoneproducing adrenal neo-plasma and, treatment principles of congenital adrenal hyperplasia (CAH).Methods: Eight cases of CAH and 5 cases of sex hormone producing adrenal neoplasma were admitted tohospital during 1986-1996. The former included 3 rare cases of 17 a hydroxylase deficiency. Thelatter included 3 cases of feminizing adrenal tumor and 2 cases of virilizing adrenal tumor.Results: Weight, size and CT of the tumor, DHEA, 17 -ks, sex hormone levels, infiltration, andmetastasis were closely related to the degree of differentiation of the tumors. Conclusion:Virilizing and feminizing adrenal neoplasm were removed surgically by different incisions. Modifiedsubcostal incision was recommended as the best choice for huge adrenal mass. Corticoadrenal hormonetreatment fa CAH should be individualized according to the different types of the disease. Sexhormones were not suitable for children suffering from 17 hydroxylase deficiency before puberty.

肾上腺Castleman病1例

Castleman病(CD)是一种罕见的淋巴增生性疾病,累及肾上腺者较为罕见。本文报道1例右肾上腺CD,查体发现右肾上腺占位,行后腹腔镜下右肾上腺肿瘤切除术,病理诊断为肾上腺淋巴组织增生,符合CD(混合型)。通过分析该患者的临床特点、相关检查及术后病理,结合相关文献介绍CD的临床特点及诊疗方法,以提高对此病的临床认识。

肾上腺结节影像报告和数据系统的分类建议及进展

肾上腺结节是一种常见的肾上腺疾病,其影像学诊断在临床中起重要作用。目前,对肾上腺结节在影像学上的良恶性风险评估分类并不统一,通过探索肾上腺结节影像报告和数据系统(AI-RADS)的分类方法,可将肾上腺结节按大小及影像学特征分为微小、小、中等、大结节以及良、恶性结节。当结节为良性且为微小或小结节时,无须进行随访;但若结节表现出恶性特征且为中等或大结节时,则应考虑影像随访或进一步手术治疗。AI-RADS作为一种新兴的影像学评估系统,为肾上腺结节的规范化诊断提供了新的途径。未来建议集中优化AI-RADS,提高其准确性和可靠性,同时探索AI-RADS的进一步应用和推广,以促进肾上腺结节的早期诊断和个性化治疗。