P-450c17mRNA在原发性醛固酮增多症肾上腺皮质腺瘤及增生组织中的表达及意义

为探讨细胞色素P-450 c17 -羟化酶(P-450 c17 )mRNA 在原发性醛固酮增多症(原醛)肾上腺皮质腺瘤（APA）及增生组织中的表达及其意义，采用 Northern Blot 法对7 例APA 组织，3 例结节样增生组织，7 例正常肾上腺组织，1 例腹壁骨骼肌组织P-450 c17 mRNA 的表达水平进行检测。结果显示P-450 c17 mRNA 在原醛APA组织与正常肾上腺组织中的表达有显著性差异P<0.05。P-450 c17 mRNA 在原醛肾上腺皮质增生组织与正常肾上腺组织中的表达、在原醛APA 组织与原醛肾上腺皮质增生组织中的表达相似。提示P-450 c17 mRNA 在APA 组织中的表达降低很可能是原醛APA 组织分泌过多醛固酮(ALD)的分子生物学原因。     

肾上腺皮质腺瘤与增生的神经内分泌分化特性

目的 :探讨肾上腺皮质腺瘤及增生有无神经内分泌性分化。方法 :通过免疫组化方法观察肾上腺皮质腺瘤 (n =39)、增生 (n =2 4)、正常组 (n =10 )的神经丝蛋白 (NF)、神经特异性烯化酶 (NSE)、突触素 (SY)的阳性表达。结果 :腺瘤组NF阳性率35 .89% ,NSE 6 6 .6 6 % ,SY 6 1.5 3%。肾上腺皮质增生的阳性率分别为NF 12 .5 % ,NSE 37.5 % ,SY 5 0 %。且所有阳性表达均发生于伴有结节性增生的病例。与正常组比较SY阳性表达有显著意义 (P <0 .0 5 ) ,与腺瘤组比较NSE阳性表达有显著意义 (P<0 .0 5 )。结论 :肾上腺皮质腺瘤与伴有结节增生的肾上腺皮质增生有神经内分泌分化     

KDM1A inactivation causes hereditary food-dependent Cushing syndrome

PurposeThis study aimed to investigate the genetic cause of food-dependent Cushing syndrome (FDCS) observed in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) and adrenal ectopic expression of the glucose-dependent insulinotropic polypeptide receptor. Germline ARMC5 alterations have been reported in about 25% of PBMAH index cases but are absent in patients with FDCS.MethodsA multiomics analysis of PBMAH tissues from 36 patients treated by adrenalectomy was performed (RNA sequencing, single-nucleotide variant array, methylome, miRNome, exome sequencing).ResultsThe integrative analysis revealed 3 molecular groups with different clinical features, namely G1, comprising 16 patients with ARMC5 inactivating variants; G2, comprising 6 patients with FDCS with glucose-dependent insulinotropic polypeptide receptor ectopic expression; and G3, comprising 14 patients with a less severe phenotype. Exome sequencing revealed germline truncating variants of KDM1A in 5 G2 patients, constantly associated with a somatic loss of the KDM1A wild-type allele on 1p, leading to a loss of KDM1A expression both at messenger RNA and protein levels (P = 1.2 × 10^–12 and P < .01, respectively). Subsequently, KDM1A pathogenic variants were identified in 4 of 4 additional index cases with FDCS.ConclusionKDM1A inactivation explains about 90% of FDCS PBMAH. Genetic screening for ARMC5 and KDM1A can now be offered for most PBMAH operated patients and their families, opening the way to earlier diagnosis and improved management.     

肾上腺皮质肿瘤中 NF-κB 的表达及意义

目的 探讨NF-κB在肾上腺皮质肿瘤中的表达及其临床意义. 方法 用免疫组化法检测肾上腺疾病标本（肾上腺皮质癌15例,肾上腺皮质瘤30例,肾上腺皮质增生11例,正常肾上腺皮质组织7例）中NF-κB的表达. 结果 NF-кB在肾上腺皮质癌组中阳性表达为9/15例,其中2例（＋ ＋ ＋）,4例（＋ ＋）,3例（＋）,6例（-）;在肾上腺皮质瘤组中,NF-кB阳性表达8/30例,其中0例（＋ ＋ ＋）,2例（＋ ＋）,6例（＋）,22例（-）;增生组有2例阳性,均为（＋）;在正常组中未检测出阳性.在肾上腺皮质癌组中的表达明显高于在其他组中的表达,肾上腺皮质癌组与肾上腺皮质瘤组相比较,差异有统计学意义（P〈0.01）. 结论 NF-кB对肾上腺皮质癌的诊断具有重要意义.     

Adrenocortical response to mating, social interaction and restraint in the female Japanese quail

In some species, the act of mating may be the only occasion when a female judges the male and the course of the sexual encounter might influence forms of maternal investment that are mediated by hormonal pathways. Despite the growing interest in fitness consequences of acute adrenocortical responses, it has not been determined to what extent the act of mating provokes such responses in females. We used female Japanese quail (Coturnix japonica) to determine to what extent any increase in corticosterone (CORT) is specific to actually mating with a male compared to visual and auditory contact with a male, and compared to social interaction with a female. We also asked if greater mating experience decreases the CORT response. We assessed how body condition of the individuals and their behavior during testing contributed to the variation in CORT response. As an additional reference for CORT increase we used a restraint procedure which resulted in the highest CORT. Our results show that females mating with a male have plasma CORT concentrations significantly increased from the baseline, which is not the case in females interacting with a male without the possibility of mating. Greater previous mating experience does not affect the CORT change caused by sexual interaction. Interestingly, social interaction with a female elicited a similar CORT response as mating with a male, which suggests that the effect on CORT was due to direct social interactions per se and not specific to the act of mating. Behavior during social and sexual interactions did not predict the CORT response, but larger females exhibited lower baseline and response CORT concentrations. We suggest that the lesser adrenocortical response of larger females might be related to their better control of the course of mating and might help them to adjust their reproductive investment, as reported in earlier studies.     

Outcome of adrenocortical tumors in children

Purpose

This study reviews adrenocortical tumors in children to determine factors that significantly affect outcome.

Methods

An institutional review board-approved retrospective review from 1976 to 2005 identified 23 patients younger than 19 years old with histologic confirmation of adrenocortical carcinoma (ACC) and adenomas.

Results

The mean age of the 23 children was 9.0 ± 1.6 years; girls predominated (female-to-male ratio = 1.9:1) as did cancers (ACC 16, adenoma 7); tumor hormone production (74%); and advanced stage for disease (66%). All malignancies were more than 2.5 cm. Adrenalectomy, including en bloc resection of adjacent structures (35%) achieved grossly negative margins in 70% of patients. Three patients received chemotherapy or chemoradiation as primary treatment without surgery. There was no perioperative mortality; morbidity was 10% (pneumothorax, acute renal failure, chylous ascites, and thrombocytosis). Surgical cure without adjuvant therapy was achieved for all adenomas and ACC stages I and II. For ACC stage III and IV, median survival was 21 months, 5-year survival was 0%. All advanced-staged ACC received adjuvant therapy. Surgically negative margins conferred a survival advantage.

Conclusions

Children, especially females with ACC present with large advanced-staged tumors. Surgically negative margins with or without en bloc resection improves survival. The high percentage of children with functioning tumors suggests earlier detection is possible.     

Adrenocortical function during septic shock

Objective To investigate, in patients with severe septic shock, the adrenocortical function assessed by daily plasma cortisol determinations during the first 72 h and by the short synthetic ACTH stimulation test performed within 24 h of the onset of shock. Design Prospective clinical investigation. Setting Medical intensive care unit in a university teaching hospital. Patients 40 consecutive patients with documented septic shock requiring at least hemodynamic resuscitation and respiratory support. Interventions There were no intervention. Measurements and results Basal cortisol concentrations were increased with a mean value of 36.8 μg/dl (range 7.9–113). Of the overall cortisol determinations 92% were above 15 μg/dl. No statistically significant differences in basal cortisol concentrations were found when survival, type of infection, and positive blood cultures were considered. Patients with hepatic disease had significantly higher cortisol (50.1(±6.2) μ/dl versus 35.9(±3.3) μg/dl,p=0.035) levels compared to other patients. No correlations were found between basal plasma cortisol concentrations and factors such as SAPS, OSF, hemodynamic measurements, duration of shock, and amount of vasopressor and/or inotropic agents. Cortisol concentrations had significant but weak correlation with ACTH levels in survivors (r=0.4;p=0.03;n=28) but not in non-survivors (r=0.03;p=0.85;n=52). Cortisol levels in non-survivors increased significantly from enrollment time to the 72nd hour of the survey (day 1: 38.9(±3.8) μg/dl versus day 3: 66.7(±17.1) μg/dl;p=0.046) and were significantly higher than those recorded in survivors. Responses to the short ACTH stimulation test were not significantly different between survivors and non-survivors. According to the different criteria used to interpret the response to the ACTH stimulation test, incidence of adrenocortical insufficiency was highly variable ranging from 6.25–75% in patients with septic shock. Only one patient had absolute adrenocortical insufficiency (basal cortisol level below 10 μg/dl; response to the ACTH stimulation test below 18 μg/dl. Conclusion Our data suggest that in a selected population of patients with severe septic shock single plasma cortisol determination has no predictive value. The short ACTH stimulation test performed within the first 24 h of onset shock can neither predict outcome nor estimate impairment in adrenocortical function in patients with high basal cortisol level. Adrenal insufficiency is rare in septic shock and should be suspected when cortisol level is below 15 μg/dl and then confirmed by a peak cortisol level lower than 18 μg/dl during the short ACTH stimulation test.     

Laparoscopic approach to a large adrenocortical oncocytoma: A case report and review of the literature

INTRODUCTIONAdrenocortical oncocytomas are extremely rare tumors, considered to be non-functional and of low malignant potential. Despite the great advance in laparoscopic techniques, there are extremely limited reports of laparoscopic approach of adrenocortical oncocytomas. Herein is presented a challenging case of laparoscopic approach to a large adrenocortical oncocytoma, underlining the safety and feasibility of laparoscopy in the surgical management of these extremely rare adrenal tumors.PRESENTATION OF CASEA 34 year-old male was referred for surgical evaluation after the incidental discovery of a large right adrenal mass, during ultrasound examination due to renal colic. Further imaging evaluation revealed a well circumscribed capsule around the mass was demonstrated, with no evidence of infiltration of the neoplasm to periadrenal tissues. The patient was scheduled for laparoscopic right adrenalectomy, running an uneventful postoperative period. Histopathology revealed the presence of an adrenal oncocytoma.DISCUSSIONRecent studies have demonstrated that approximately one third of adrenocortical oncocytomas are associated with hormonal hypersecretion, as well as that one fifth of them demonstrate malignant biological behavior. From this point of view, there is emerging evidence in favor of the necessity of surgical excision as the treatment of choice. In spite of the progress of laparoscopic surgery, only three cases of laparoscopic excision of these tumors have been reported up to date.CONCLUSIONLaparoscopic surgery offers a safe alternative in confronting adrenocortical neoplasms, even when the biological behavior of the tumors cannot be pre-operatively evaluated in a definite way.