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Frontiers in Endocrinology 2022In recent years, vitamin D has become the protagonist in many studies. From cardiology to oncology the spotlight was on this vitamin. While in the past it was considered... (Review)
Review
In recent years, vitamin D has become the protagonist in many studies. From cardiology to oncology the spotlight was on this vitamin. While in the past it was considered for its important role in phospho-calcium metabolism and skeletal disorders; today by studying it better, thousands of scenarios and facets have opened up on this vitamin which is actually a hormone in all respects. There are authoritative studies that demonstrate its activity and on: carcinogenesis, inflammation, autoimmunity and endocrinopathies. Its role has been studied in type 1 and type 2 diabetes mellitus, in Hashimoto or Graves' thyroiditis and even in adrenal gland diseases. In fact, there are several studies that demonstrate the possible correlations between vitamin D and: Addison's disease, Cushing disease, hyperaldosteronism or adrenocortical tumors. Moreover, this fascinating hormone and adrenal gland even seem to be deeply connected by common genetic pathways. This review aimed to analyze the works that have tried to study the possible influence of vitamin D on adrenal diseases. In this review we analyze the works that have tried to study the possible influence of vita-min D on adrenal disease.
Topics: Humans; Vitamin D; Diabetes Mellitus, Type 2; Adrenal Glands; Hyperaldosteronism; Vitamins; Hormones
PubMed: 36313775
DOI: 10.3389/fendo.2022.1001065 -
Endocrinology and Metabolism (Seoul,... Dec 2020The adrenal gland plays a pivotal role in an organism's health span by controlling the endocrine system. Decades of research on the adrenal gland have provided... (Review)
Review
The adrenal gland plays a pivotal role in an organism's health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.
Topics: Adrenal Cortex; Adrenal Glands; Adult; Animals; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Regeneration; Signal Transduction; Stem Cells
PubMed: 33397037
DOI: 10.3803/EnM.2020.403 -
The Journal of Clinical Endocrinology... Feb 2022Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require... (Observational Study)
Observational Study
CONTEXT
Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need.
OBJECTIVE
This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma.
METHODS
This retrospective cross-sectional study, which took place at 7 European tertiary-care centers, comprised 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma (PHEO), primary aldosteronism (PA), autonomous cortisol secretion (ACS), and nonfunctional adrenal incidentaloma (NFAI). Mesaures of diagnostic performance were assessed (with [95% CIs]) for discriminating different subgroups of patients with adrenal incidentaloma.
RESULTS
Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol, and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA, and PHEO at respective sensitivities of 83.3% (66.1%-100%), 90.8% (83.7%-97.8%), and 94.8% (89.8%-99.8%); and specificities of 98.0% (96.9%-99.2%), 92.0% (89.6%-94.3%), and 98.6% (97.6%-99.6%). With the addition of tumor size, discrimination improved further, particularly for ACC (100% [100%-100%] sensitivity, 99.5% [98.9%-100%] specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70%-71% sensitivity, 89%-90% specificity).
CONCLUSION
Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate the identification of almost all clinically relevant adrenal tumors.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenocortical Carcinoma; Adult; Aged; Cross-Sectional Studies; Diagnosis, Differential; Female; Humans; Hyperaldosteronism; Male; Metanephrine; Middle Aged; Pheochromocytoma; Retrospective Studies; Steroids; Tumor Burden
PubMed: 34665854
DOI: 10.1210/clinem/dgab751 -
The Journal of Clinical Endocrinology... Aug 2022The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that strongly express aldosterone...
CONTEXT
The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters (APCCs) that strongly express aldosterone synthase (CYP11B2) are frequently found in adult adrenals and harbor somatic mutations that are also detected in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA). We presume that APCCs are causing IHA and are precursors of APAs. However, the gene expression characteristics and especially the development of APCCs are not well understood.
OBJECTIVE
This study aimed to analyze the transcriptome of APCCs at single-cell resolution and infer the developmental trajectory.
METHODS
Single-cell RNA sequencing (scRNA-seq) of 2 adult adrenals was performed.
RESULTS
Immunohistochemical analyses confirmed the 2 adrenals had APCCs. scRNA-seq data of 2928 adrenal cells were obtained and 1765 adrenocortical cells were identified based on unsupervised clustering and the marker gene expression. The adrenocortical cells were divided into 6 clusters, of which 3 clusters (923 cells) were composed of APCC/ZG cells. By further subclustering, the APCC/ZG cells were divided into 3 clusters (clusters C1, C2, and C3), we finally identified APCC cluster (C3) and ZG cluster (C1). Cluster C2 seemed to be ZG-to-ZF transitional cells. RNA velocity analysis inferred the developmental direction from cluster ZG-cluster-C1 to APCC-cluster-C3. The scRNA-seq additionally revealed that many CYP11B2-positive cells were positive for CYP11B1 and/or CYP17A1, which were essential for cortisol but not for aldosterone production.
CONCLUSIONS
Our results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel to APCC.
Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Glands; Adult; Aldosterone; Cytochrome P-450 CYP11B2; Humans; Hyperaldosteronism; Zona Glomerulosa
PubMed: 35796577
DOI: 10.1210/clinem/dgac394 -
Chirurgie (Heidelberg, Germany) Mar 2024Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment... (Review)
Review
BACKGROUND
Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma.
MATERIAL AND METHODS
A narrative review article based on the most recent literature is presented.
RESULTS AND DISCUSSION
The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24‑h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.
Topics: Humans; Pheochromocytoma; Precision Medicine; Adrenal Gland Neoplasms; Adrenal Glands; Metanephrine
PubMed: 37957403
DOI: 10.1007/s00104-023-01988-6 -
The American Journal of Tropical... Sep 2020
Topics: Adrenal Glands; Amphotericin B; Asthenia; Diarrhea; Fludrocortisone; Humans; Hydrocortisone; Itraconazole; Male; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Tomography, X-Ray Computed; Vomiting
PubMed: 32896237
DOI: 10.4269/ajtmh.20-0083 -
Annals of Medicine Dec 2023This study aimed to identify the appropriate signature veins for the right adrenal gland using a 3D model fused with adrenal venography images and to verify their...
BACKGROUND
This study aimed to identify the appropriate signature veins for the right adrenal gland using a 3D model fused with adrenal venography images and to verify their accuracy through the selectivity index (SI) >2.
METHODS
We analyzed the right adrenal venography images of 41 patients who underwent adrenal venous sampling (AVS). These images were merged with a 3D structure of the adrenal gland to identify the signature veins of the right adrenal gland. We then used the signature veins observed during adrenal venography to determine the optimal position of the catheter tip during AVS for 53 other patients. Finally, we verified the accuracy of this method according to the SI.
RESULTS
We successfully fused the 3D models of 41 cases with adrenal venography images. We identified the trunk branch type as the major venous morphology in the right anterior oblique at degrees of 30 (38 cases, 92.7%). In addition, the central vein, brush vein, uvula vein, and capsular vein were identified as signature veins for the right AVS. The accuracy of AVS was 100% in the other 53 patients, as verified by an SI >2.
CONCLUSIONS
Our study identified the right adrenal signature veins, including the previously overlooked uvula vein, which can be used to determine the position of the catheter tip and improve the success rate of AVS.
Topics: Humans; Hyperaldosteronism; Catheterization; Adrenal Glands; Phlebography; Retrospective Studies; Aldosterone
PubMed: 37452706
DOI: 10.1080/07853890.2023.2234934 -
Endocrinology and Metabolism (Seoul,... Dec 2020The agenesis of the gonads and adrenal gland in revealed by knockout mouse studies strongly suggested a crucial role for Nr5a1 (SF-1 or Ad4BP) in organ development. In... (Review)
Review
The agenesis of the gonads and adrenal gland in revealed by knockout mouse studies strongly suggested a crucial role for Nr5a1 (SF-1 or Ad4BP) in organ development. In relation to these striking phenotypes, NR5A1/Nr5a1 has the potential to reprogram cells to steroidogenic cells, endow pluripotency, and regulate cell proliferation. However, due to limited knowledge regarding NR5A1 target genes, the mechanism by which NR5A1/Nr5a1 regulates these fundamental processes has remained unknown. Recently, newlyestablished technologies have enabled the identification of NR5A1 target genes related to multiple metabolic processes, as well as the aforementioned biological processes. Considering that active cellular processes are expected to be accompanied by active metabolism, NR5A1 may act as a key factor for processes such as cell differentiation, proliferation, and survival by coordinating these processes with cellular metabolism. A complete and definite picture of the cellular processes coordinated by NR5A1/Nr5a1 could be depicted by accumulating evidence of the potential target genes through whole genome studies.
Topics: Adrenal Glands; Animals; Biological Phenomena; Cell Differentiation; Cell Proliferation; Glycolysis; Gonads; Humans; Mice; Mice, Knockout; Phenotype; Steroidogenic Factor 1
PubMed: 33397036
DOI: 10.3803/EnM.2020.402 -
Frontiers in Endocrinology 2022The adrenal gland is a common organ involved in metastasis. This study aimed to compare adrenal metastases (AMs) and adrenal benign masses (ABMs) of patients with...
BACKGROUND AND OBJECTIVES
The adrenal gland is a common organ involved in metastasis. This study aimed to compare adrenal metastases (AMs) and adrenal benign masses (ABMs) of patients with extra-adrenal malignancies during the staging or follow-up.
METHODS
We retrospectively collected data from 120 patients with AMs and 87 patients with ABMs. The clinical characteristics, imaging features, pathology, and treatment regimes were analyzed.
RESULTS
The most common types of extra-adrenal malignancies in patients with ABMs included thyroid, kidney, and gynecological cancers. On the other hand, lung and kidney cancers and lymphoma were the most frequent primary cancers of AMs. The age and incidence of symptoms were significantly higher in patients with AM. Radiological analysis showed that AMs tended to have larger tumor sizes and higher attenuation values than ABMs on pre-contrast computed tomography (CT). The diagnostic accuracy of positron emission tomography-CT for AM was 94.1%. An adrenal biopsy had a diagnostic accuracy of 92.5%. A multivariate logistic regression model demonstrated that the origins of extra-adrenal malignancies, the enhancement pattern, and attenuation values in pre-contrast CT were independent predictors of AMs. The sensitivity and specificity of this predictive model of combination was 92.5% and 74.1%, respectively.
CONCLUSIONS
The differential diagnosis between AMs and ABMs is extremely important. The combination of origin of first malignancy, enhancement pattern and CT value in non-enhanced phase is a valuable model for predicting AMs.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Diagnosis, Differential; Humans; Neoplasms, Second Primary; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 36246921
DOI: 10.3389/fendo.2022.978730 -
International Journal of Molecular... Mar 2023The adrenal glands are important endocrine organs that play a major role in the stress response. Some adrenal glands abnormalities are treated with hormone replacement... (Review)
Review
The adrenal glands are important endocrine organs that play a major role in the stress response. Some adrenal glands abnormalities are treated with hormone replacement therapy, which does not address physiological requirements. Modern technologies make it possible to develop gene therapy drugs that can completely cure diseases caused by mutations in specific genes. Congenital adrenal hyperplasia (CAH) is an example of such a potentially treatable monogenic disease. CAH is an autosomal recessive inherited disease with an overall incidence of 1:9500-1:20,000 newborns. To date, there are several promising drugs for CAH gene therapy. At the same time, it remains unclear how new approaches can be tested, as there are no models for this disease. The present review focuses on modern models for inherited adrenal gland insufficiency and their detailed characterization. In addition, the advantages and disadvantages of various pathological models are discussed, and ways of further development are suggested.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Adrenal Glands; Mutation; Incidence
PubMed: 36982440
DOI: 10.3390/ijms24065365