原发性色素性结节状肾上腺皮质病的临床病理特征:附5例报道

目的:回顾性研究5例原发性色素性结节状肾上腺皮质病(PPNAD)的临床病理特征。方法:分析临床和实验室资料,对病变组织行HE染色和免疫组化标记。结果:本组5例患者临床诊断为库欣综合征,其中4例合并Carney综合征;1例为特发性。病理学表现为多发性色素性皮质结节伴结节间皮质萎缩;镜检观察到两种细胞,一种为含有嗜酸性细胞质和脂褐素的大细胞,另一种为细胞质富含脂质,空泡状。这些细胞免疫组化标记神经元特异性烯醇化酶阳性(++)。结论:PPNAD可造成促肾上腺皮质激素(ACTH)非依赖性皮质醇增多症。且多数患有Carney综合征。     

Ferroptosis‐based molecular prognostic model for adrenocortical carcinoma based on least absolute shrinkage and selection operator regression

BackgroundThis study aimed to find ferroptosis‐related genes linked to clinical outcomes of adrenocortical carcinoma (ACC) and assess the prognostic value of the model.MethodsWe downloaded the mRNA sequencing data and patient clinical data of 78 ACC patients from the TCGA data portal. Candidate ferroptosis‐related genes were screened by univariate regression analysis, machine‐learning least absolute shrinkage, and selection operator (LASSO). A ferroptosis‐related gene‐based prognostic model was constructed. The effectiveness of the prediction model was accessed by KM and ROC analysis. External validation was done using the {"type":"entrez-geo","attrs":{"text":"GSE19750","term_id":"19750"}}GSE19750 cohort. A nomogram was generated. The prognostic accuracy was measured and compared with conventional staging systems (TNM stage). Functional analysis was conducted to identify biological characterization of survival‐associated ferroptosis‐related genes.ResultsSeventy genes were identified as survival‐associated ferroptosis‐related genes. The prognostic model was constructed with 17 ferroptosis‐related genes including STMN1, RRM2, HELLS, FANCD2, AURKA, GABARAPL2, SLC7A11, KRAS, ACSL4, MAPK3, HMGB1, CXCL2, ATG7, DDIT4, NOX1, PLIN4, and STEAP3. A RiskScore was calculated for each patient. KM curve indicated good prognostic performance. The AUC of the ROC curve for predicting 1‐, 3‐, and 5‐ year(s) survival time was 0.975, 0.913, and 0.915 respectively. The nomogram prognostic evaluation model showed better predictive ability than conventional staging systems.ConclusionWe constructed a prognosis model of ACC based on ferroptosis‐related genes with better predictive value than the conventional staging system. These efforts provided candidate targets for revealing the molecular basis of ACC, as well as novel targets for drug development.     

人肾上腺皮质癌裸鼠腹腔种植转移模型的建立及意义

目的：建立人肾上腺皮质癌裸鼠腹腔种植转移模型并探讨其生物学特性。方法：将1×10^6/mL体外培养的人肾上腺皮质癌SW-13细胞悬液接种于10只裸鼠腹腔内,分别于接种后第2、3周随机处死3只裸鼠,余下裸鼠于第4周全部处死取材。动态观察裸鼠体内成瘤及组织浸润转移情况,对肿瘤组织和可疑转移脏器进行病理形态学观察及免疫组化检测Ki67的表达。结果：10只裸鼠接种第8天于接种部位成瘤率100%,接种后3、4周裸鼠腹腔内均可见到转移瘤结节,以肠系膜最为显著,转移率均为100%,第4周时可见到2只裸鼠肾转移,1只裸鼠胰腺转移。镜下发现受侵犯的肠系膜淋巴结大部分被破坏,受累的肾、胰腺组织有明显肿瘤细胞浸润。SW-13细胞在体内外均高表达Ki67。结论：成功构建人肾上腺皮质癌裸鼠腹腔种植转移模型,为深入研究肾上腺皮质癌浸润转移机制及防治研究提供较为理想的动物模型。     

原发性色素沉着性结节性肾上腺皮质病1例报道及文献回顾

目的:分析探索原发性色素沉着性结节性肾上腺皮质病（primary pigmented nodular adrenocortical disease,PPNAD）的临床表现、实验室检查特点、辅助检查特征及诊疗方案。方法:对空军军医大学第一附属医院泌尿外科收治的1例PPNAD患者的临床资料及国内文献所报道的46例患者临床资料进行回顾性分析。46例患者中男性16例,女性30例;其中44例表现为典型库欣综合征体貌,2例仅表现为高血压;伴Carney综合征(Carney complex,CNC)者16例,2例有甲状腺占位;疾病确诊年龄为11~58岁。实验室检查证实患者均具备促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）非依赖性特征,大、小剂量地塞米松抑制试验均不被抑制者45例,1例被抑制,16例患者服用地塞米松后尿游离皮质醇（urinary free cortisol,UFC）升高。影像学完善头部MRI检查者发现垂体占位性病变者2例,无病变者20例,肾上腺CT检查可有双侧肾上腺多发结节或增粗、单侧肾上腺结节或肿物、单侧肾上腺增粗或未见明显变化等表现。治疗方式有腹腔镜下双侧肾上腺全切术、单侧肾上腺肿物切除术及单侧肾上腺全切术。结果:双侧肾上腺切除术联合术后终身激素替代治疗疗效确切,无复发;肾上腺次全切除术和单侧肾上腺切除术后无需激素替代治疗,但存在一定的复发风险。结论:PPNAD临床罕见,确诊主要依据病理检查,对于影像学检查阳性的非依赖性ACTH患者应高度怀疑本病。腹腔镜下双侧肾上腺切除联合术后激素替代治疗是目前治疗PPNAD的合理方案,具体术式应根据患者自身情况拟定。     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.     

A simple and efficient automated cGMP‐compliant radiosynthesis of [11C]metomidate using solid phase extraction cartridge purification

[¹¹C]metomidate ([¹¹C]MTO) is a radiotracer widely used to detect disorders of adrenocortical origin by positron emission tomography (PET) imaging. [¹¹C]MTO PET/computed tomography (PET/CT) is considered a sensitive and specific noninvasive alternative to adrenal vein sampling (AVS) in the management of primary hyperaldosteronism (PHA). Herein, we report a reliable automated procedure for the routine manufacturing of [¹¹C]MTO in current good manufacturing practice (cGMP) conditions on the commercial Synthra MeI_Plus Loop Vessel synthesizer. The method is based on a combination of the captive‐solvent ¹¹C‐methylation of the carboxylate salt 1b of the MTO precursor 1a followed by solid phase extraction (SPE) cartridge purification methodology, which substitutes HPLC purification of the crude reaction mixture. Starting from 45 GBq [¹¹C]CO₂ at the end of bombardment (EOB), 3 GBq of pure [¹¹C]MTO was produced in 18 minutes with 12% decay corrected radiochemical yield (RCY) at the end of synthesis (EOS) and with the modest molar activity of 13 GBq/μmol at the time of application. Each dose produced met all established quality control (QC) criteria. The method can easily be implemented into other commercial automated radiosynthesizers for manufacturing carbon‐11 labeled radiotracers.     

Involvement of the sensory cortex in adrenocortical responses following photic and acoustic stimulation in the rat

In order to examine the possibility that the sensory cortex participates in the mediation of adrenocortical responses following sensory stimuli, the effects of photic and acoustic stimuli on plasma corticosterone were studied in rats with either visual or auditory cortex ablation. In animals with visual cortex ablation, the adrenocortical response to acoustic stimuli was intact; however, it was significantly reduced following photic stimulation. On the other hand, in animals with auditory cortex ablation, the response to acoustic stimulation was significantly reduced, but the response to photic stimulation remained intact. These data demonstrate the participation of the specific sensory cortex in adrenocortical responses following the stimulation of the corresponding sensory modality. The possible mechanisms involved may be either a tonic facilitatory effect of the specific cortex on subcortical mechanisms or the transmission of the specific stimuli in the primary sensory pathways, to achieve a full adrenocortical discharge.