MiRNA expression in plasma samples from Non-functional adenoma (NFA), Cortisol-producing adneoma (CPA)and primary bilateral macronodular adrenal hyperplasia (PBMAH)
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PROVIDER: PRJNA908756 | ENA |
REPOSITORIES: ENA
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Project description:To investigate circulating miRNA expression sinatures of PBMAH, we collected plasma samples of patients with PBMAH and other phenotypes of adrenal diseases including NFA and CPA. MiRNAs were extracted from plasma samples and its expression signatures were examined.
2022-12-08 | GSE220070 | GEO
Project description:Expression studies familial bilateral macronodular adrenal hyperplasia
| PRJNA720089 | ENA
Project description:Background: Autonomous cortisol secretion (ACS), results from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, how other adrenal steroid metabolites affect bone status is unclear. Methods: ACS was diagnosed at serum cortisol after 1-mg dexamethasone suppression test (DST-cortisol) ≥ 1.8 g/dL. Using liquid chromatography-tandem mass spectrometry, we measured 21 plasma steroid metabolites in 73 patients with ACS and 85 with non-functioning adrenal tumors (NFAT). We also examined expression of steroidogenic enzymes and relevant steroid metabolites in some of CPA tissues. Results: In discriminant and principal component analysis, steroid profiles distinguished between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite; 11-deoxycorticosterone (11-DOC), with lower androgen metabolites; dehydroepiandrosterone-sulfate and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol was negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC was negatively correlated with lumbar spine-bone mineral density (r = -0.603), while androsterone-glucuronide was positively correlated with TBS (r = 0.681), which was supported by Bayesian kernel machine regression analysis. There were no such correlations in postmenopausal women and men. The CPA tissues showed increased levels of 11-DOC, with increased expression of CYP21A2, which is essential for 11-DOC synthesis. The adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, which is required for androgen synthesis. Conclusion: This study provides the first evidence that unbalanced production of adrenal steroid metabolites, which are derived from both adrenal tumors and non-tumor tissues, play a role in the pathogenesis of endogenous SIOP in premenopausal women with ACS.
2023-06-01 | E-MTAB-12895 | biostudies-arrayexpress
Project description:BackgroundPrimary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare condition with untypical subclinical symptoms of Cushing's syndrome (CS). This study aimed to compare the clinical and pathological features of PBMAH with unilateral cortisol-secreting adrenal adenoma (UAA).MethodsWe prospectively included 46 PBMAH patients and 205 UAA patients from January 2000 to February 2014. Cortisol levels and 24 hours urine free cortisol (UFC) were determined at baseline and during dexamethasone suppression test (DST) using the chemiluminescence method. Computed tomography (CT) examination of the adrenal glands was performed in all patients. For patients treated with adrenalectomy, hematoxylin, and eosin, staining was performed for pathological examination.ResultsThe proportion of patients with autonomous cortisol secretion was significantly higher in PBMAH patients (39.1%) than UAA patients (6.8%). The PBMAH patients showed significantly lower levels of basal cortisol, low dose dexamethasone suppressed cortisol, and high dose dexamethasone suppressed cortisol than the UAA patients (452.6±183.3 vs. 578.7±166.4 nmol/L, P=0.003; 394.5±298.9 vs. 549.2±217.7 nmol/L, P=0.002; 397.3±282.3 vs. 544.3±187.6 nmol/L, P=0.003). Similarly, the PBMAH patients had significantly lower levels of basal 24 hours UFC, low dose dexamethasone suppressed 24 hours UFC, and high dose dexamethasone suppressed 24 hours UFC than the UAA patients (1,144.4±1,048.1 vs. 1,674.9±1,520.4 nmol/24 h, P=0.032; 1,157.3±1,483.5 vs. 1,940.1±1,360.9 nmol/24 h, P=0.003; 1,256.4±1,767.0 vs. 1,969.9±1,361.7 nmol/24 h, P=0.011).ConclusionsPBMAH is often associated with atypical CS symptoms. The clinical and imaging features of PBMAH are useful for the differential diagnosis of this disease.
| S-EPMC7576081 | biostudies-literature
Project description:CONTEXT: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome. OBJECTIVE: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. DESIGN AND SETTING: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. INTERVENTION: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. MAIN OUTCOME MEASURE: Detection of 17alpha-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. RESULTS: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17alpha-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. CONCLUSION: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing's syndrome.
| S-EPMC2805485 | biostudies-literature
Project description:AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia). Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples. Copy number and LOH analysis of Affymetrix SNP6 arrays was performed for AIMAH nodules from 26 patients, including 18 with paired leucocyte and nodules (1 to 4 nodules per patient), and 8 with a single nodule (no paired leucocyte available)
2013-11-28 | E-GEOD-42171 | biostudies-arrayexpress
Project description:AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia). Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples.
2013-11-28 | GSE42171 | GEO
Project description:PRKAR1A inactivating mutations are responsible for primary pigmented nodular adrenocortical disease (PPNAD) whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome (MAS), ACTH-independent hyperplasia (AIMAH) and, rarely, cortisol-producing adenomas (CPA). The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied.
2011-11-15 | GSE33694 | GEO
Project description:PRKAR1A inactivating mutations are responsible for primary pigmented nodular adrenocortical disease (PPNAD) whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome (MAS), ACTH-independent hyperplasia (AIMAH) and, rarely, cortisol-producing adenomas (CPA). The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied. Total RNA obtained from adrenal tumors were compared to those samples obtained from normal adrenal pools
2011-11-15 | E-GEOD-33694 | biostudies-arrayexpress
Project description:The objectives were to determine the molecular mechanisms involved in the development and progression of familial BMAH tumours, and the mechanisms of their inefficient steroidogenesis.
2021-04-07 | GSE171558 | GEO