scholarly journals Cushing Syndrome Caused by Adrenocortical Tumors and Hyperplasias (Corticotropin- Independent Cushing Syndrome)

Author(s):  
Constantine A. Stratakis
2020 ◽  
Vol 105 (12) ◽  
pp. e4605-e4615
Author(s):  
Guido Di Dalmazi ◽  
Luca Morandi ◽  
Beatrice Rubin ◽  
Catia Pilon ◽  
Sofia Asioli ◽  
...  

Abstract Context DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism. Objective The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors. Design and Setting This cross-sectional study took place at university hospitals. Patients We collected fresh-frozen tissues from patients with benign adrenocortical adenomas (n = 48) (nonfunctioning n = 9, autonomous cortisol secretion n = 9, Cushing syndrome n = 17, aldosterone-producing [APA] n = 13) and adrenal cortex adjacent to APA (n = 12). We collected formalin-fixed, paraffin-embedded (FFPE) specimens of paired APA and concurrent aldosterone-producing cell clusters (APCCs) (n = 6). Intervention DNA methylation levels were evaluated by quantitative bisulfite next-generation sequencing in fresh-frozen tissues (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO) and FFPE APA/APCC paired samples (CYP11B2). CYP11B1, CYP11B2, CYP17, CYP21, and STAR gene expressions were examined by quantitative real-time polymerase chain reaction. Main Outcome Measure The main outcome measure was DNA methylation. Results CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P < .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (ρ = –0.379; P = .003). In FFPE-paired APA/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028). Conclusions DNA methylation plays a regulatory role for CYP11B2 expression and may contribute to aldosterone hypersecretion in APA. Lower CYP11B2 methylation levels in APA than in APCCs may suggest an APCC-to-APA switch via progressive CYP11B2 demethylation. Conversely, DNA methylation seems not to be relevant in regulating the expression of genes encoding steroidogenic enzymes other than CYP11B2.


2009 ◽  
Vol 160 (1) ◽  
pp. 93-99 ◽  
Author(s):  
François Moreau ◽  
Hervé Mittre ◽  
Annie Benhaim ◽  
Camille Bois ◽  
Jérome Bertherat ◽  
...  

ObjectiveThe aromatase enzyme catalyzes the final stage of estrogen biosynthesis pathway from androgens. Its expression in the adrenal is poorly studied except for the rare estrogen-producing adrenocortical tumors. In order to further characterize aromatase expression in the adrenal, we evaluated the aromatase enzyme activity, Cyp19a1 gene expression level, and promoter utilization in normal adrenal tissues and in adrenocortical secreting tumors.Design and methodsSix normal adult adrenals (NA), 2 feminizing adrenal tumors (FT), 10 cortisol-producing adenomas with overt (CS, n=4) or sub-clinical Cushing syndrome (SCS, n=6) and 3 aldosterone-producing adenomas (APA) were studied. Tissue aromatase activity was determined by the tritiated (3H)-water method. Total aromatase mRNA were measured by a competitive RT-PCR. Promoter regions PII and PI.4-derived transcripts were also studied in NA, FT, and other steroid-producing tumors by a semi-quantitative comparative RT-PCR. Immunofluorescence analysis was performed in normal human adrenal tissues.ResultsAromatase activity was detected in NA tissues and in all tumor subtypes, at high levels in both FT. In NA, aromatase immunofluorescence was detected in the cytoplasm of steroidogenic cells, mainly from zona reticularis. Compared with NA, aromatase transcript levels were similar in CS and APA, lower in SCS and similar or higher in FT. Promoter analysis suggested predominant PII utilization in NA, APA, and SCS, but similar PII and PI.4 utilization in CS tumors.ConclusionAromatase is expressed at similar levels in normal adrenal and in adrenocortical tumors, but at variably high levels in FT. Different promoter utilization patterns are found among tumor subtypes.


2001 ◽  
Vol 47 (3) ◽  
pp. 26-29
Author(s):  
N. N. Molitvoslovova ◽  
Yu. Yu. Belova ◽  
P. V. Yushkov ◽  
N. S. Kuznetsov ◽  
Ye. I. Marova ◽  
...  

The article is devoted to the descripition of the rare case with Icenko-Cushing syndrome caused by multiple bilateral benign and malignant adrenocortical tumors.


2017 ◽  
Vol 23 ◽  
pp. 179
Author(s):  
Sandeep Donagaon ◽  
Pramila Kalra ◽  
Anil Kumar ◽  
K. Harish ◽  
Shamim Sheik ◽  
...  

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
B Altieri ◽  
S Sbiera ◽  
S Della Casa ◽  
S Steinhauer ◽  
V Wild ◽  
...  

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