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Surgical Oncology Clinics of North... Apr 2021Pediatric adrenal tumors are uncommon entities that are frequently occult and identified incidentally or by recognizing symptoms related to hormone overproduction. They... (Review)
Review
Pediatric adrenal tumors are uncommon entities that are frequently occult and identified incidentally or by recognizing symptoms related to hormone overproduction. They often have a genetic underpinning, arise from the medulla or cortex, can be malignant or benign, and require precise diagnostic algorithms. However, pseudotumors must also be a diagnostic consideration. Therapeutic interventions and plans are tumor dependent, but surgery is a cornerstone of treatment. Ongoing surveillance after treatment, regardless of malignant determination, is of utmost importance as well.
Topics: Adrenal Gland Neoplasms; Child; Humans
PubMed: 33706900
DOI: 10.1016/j.soc.2020.11.012 -
IUBMB Life Apr 2020Synaptic neurotransmission at the splanchnic nerve-chromaffin cell synapse is a chief element of the stimulus-secretion coupling in the adrenal medullary tissue,... (Review)
Review
Synaptic neurotransmission at the splanchnic nerve-chromaffin cell synapse is a chief element of the stimulus-secretion coupling in the adrenal medullary tissue, managing and regulating the secretion of catecholamines. Making the state of play more intricate than initially envisioned, the synaptic vesicles of nerve terminals innervating the medulla contain various compounds, including various neurotransmitters and neuropeptides. Under basal conditions associated with a low splanchnic nerve discharge rate, neurotransmission is ensured by the synaptic release of the primary neurotransmitter acetylcholine (ACh). Under sustained and repetitive stimulations of the splanchnic nerve, as triggered in response to stressors, the synaptic release of neuropeptides, such as the pituitary adenylate cyclase-activating polypeptide PACAP, supplants ACh release. The anatomical and functional changes that occur presynaptically at the preganglionic splanchnic nerve, combined with changes occurring postsynaptically at nicotinic acetylcholine receptors (nAChRs), confer the adrenomedullary synapses a solid and persistent aptitude to functional remodeling, from birth to aging. The present review focuses on the composite cholinergic and noncholinergic nature of neurotransmission occurring at the splanchnic nerve-chromaffin cell synapse and its remodeling in response to physiological or pathological stimuli.
Topics: Acetylcholine; Adrenal Medulla; Animals; Chromaffin Cells; Humans; Neuropeptides; Neurotransmitter Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Splanchnic Nerves; Synapses; Synaptic Transmission
PubMed: 31301221
DOI: 10.1002/iub.2117 -
Methods in Molecular Biology (Clifton,... 2023Chromaffin granules isolated from adrenal glands constitute a powerful experimental tool to the study of secretory vesicle components and their participation in fusion...
Chromaffin granules isolated from adrenal glands constitute a powerful experimental tool to the study of secretory vesicle components and their participation in fusion and docking processes, vesicle aggregation, and interactions with cytosolic components. Although it is possible to isolate and purify chromaffin granules from adrenal glands of different species, bovine adrenal glands are the most used tissue source due to its easy handling and the large amount of granules that can be obtained from this tissue. In this chapter, we describe an easy-to-use and short-term protocol for efficiently obtaining highly purified chromaffin granules from bovine adrenal medulla. We additionally include protocols to isolate granules from cultured bovine chromaffin cells and PC12 cells, as well as a section to obtain chromaffin granules from mouse adrenal glands.
Topics: Adrenal Glands; Adrenal Medulla; Animals; Cattle; Chromaffin Cells; Chromaffin Granules; Mice; Neuroendocrine Cells; PC12 Cells; Rats
PubMed: 36205901
DOI: 10.1007/978-1-0716-2671-9_19 -
Journal of Cellular Physiology Nov 2021Neuroblastoma (NB) is a common solid extracranial tumor developing in pediatric populations. NB can spontaneously regress or grow and metastasize displaying resistance... (Review)
Review
Neuroblastoma (NB) is a common solid extracranial tumor developing in pediatric populations. NB can spontaneously regress or grow and metastasize displaying resistance to therapy. This tumor is derived from primitive cells, mainly those of the neural crest, in the sympathetic nervous system and usually develops in the adrenal medulla and paraspinal ganglia. Our understanding of the molecular characteristics of human NBs continues to advance documenting abnormalities at the genome, epigenome, and transcriptome levels. The high-risk tumors have MYCN oncogene amplification, and the MYCN transcriptional regulator encoded by the MYCN oncogene is highly expressed in the neural crest. Studies on the biology of NB has enabled a more precise risk stratification strategy and a concomitant reduction in the required treatment in an expanding number of cases worldwide. However, newer treatment strategies are mandated to improve outcomes in pediatric patients who are at high-risk and display relapse. To improve outcomes and survival rates in such high-risk patients, it is necessary to use a multicomponent therapeutic approach. Accuracy in clinical staging of the disease and assessment of the associated risks based on biological, clinical, surgical, and pathological criteria are of paramount importance for prognosis and to effectively plan therapeutic approaches. This review discusses the staging of NB and the biological and genetic features of the disease and several current therapies including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy for NB.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasm Staging; Neuroblastoma; Radiation Dosage; Signal Transduction
PubMed: 33834508
DOI: 10.1002/jcp.30384 -
Endocrine Dec 2023Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves...
PURPOSE
Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves respectively. The underlying genetic events are elusive.
METHODS
We searched our institutional database for AS/PAS cases and reviewed the histology and clinical outcome. Comprehensive molecular work-up was performed.
RESULTS
We found reports of 4 AS/PAS cases diagnosed between 1992 and 2022 among the 1248 adrenal lesions submitted for histopathology during the same time period (0.32%). Two patients were male, two were female, and the age span was 59-80 years. Median size was 70 mm (range 50-100 mm), and from a radiology perspective, the lesions were initially suspected of malignant lesions originating from either adrenals or kidneys. Hormonal analyses were normal in all cases. Histologically, three cases were annotated as cellular AS or PAS, and one case was annotated as microcystic AS. Molecular characterization using focused next-generation sequencing did not identify SMARCB1 or NF2 mutations, alterations previously associated to schwannoma at other anatomical sites. The postoperative period was without complications for all patients, and follow-up did not show any signs of relapse or metastatic disease.
CONCLUSION
AS/PAS are rare neoplasms that are most often benign, and the molecular etiology is most likely not related to mutations in established schwannoma-related genes. Since these tumors may be misinterpreted as malignant, knowledge of this entity is essential for radiologists, endocrinologists, surgeons and pathologists.
Topics: Humans; Male; Female; Middle Aged; Aged; Aged, 80 and over; Neoplasm Recurrence, Local; Neurilemmoma; Mutation
PubMed: 37535242
DOI: 10.1007/s12020-023-03463-y -
Current Opinion in Endocrinology,... Jun 2023The adrenal glands produce some of the most essential for life hormones, including cortisol and other steroids, and catecholamines. The former is produced from the... (Review)
Review
PURPOSE OF REVIEW
The adrenal glands produce some of the most essential for life hormones, including cortisol and other steroids, and catecholamines. The former is produced from the adrenal cortex, whereas the latter is from the medulla. The two parts are anatomically and functionally distinct and it would be impossible in the context of one short article to cover all molecular updates on both the cortex and the medulla. Thus, in this review, we focus on the molecular tools available for diagnosing adrenocortical diseases, such as adrenal insufficiency, Cushing and Conn syndromes, and their potential for advancing medical care and clinical outcome.
RECENT FINDINGS
The advent of next generation sequencing opened doors for finding genetic diseases and signaling pathways involved in adrenocortical diseases. In addition, the combination of molecular data and clinicopathologic assessment might be the best approach for an early and precise diagnosis contributing to therapeutic decisions and improvement of patient outcomes.
SUMMARY
Diagnosing adrenocortical diseases can be challenging; however, the progress of molecular tools for adrenocortical disease diagnosis has greatly contributed to early detection and to meliorate patient outcomes.
Topics: Humans; Adrenal Cortex; Adrenal Glands; Adrenal Cortex Neoplasms; Hydrocortisone; Adrenal Insufficiency
PubMed: 37067987
DOI: 10.1097/MED.0000000000000809 -
Physiological Reviews Jul 2020Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best... (Review)
Review
Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best characterized and known to mediate Cl absorption and HCO secretion, largely through the anion exchanger pendrin. This exchanger is thought to act in tandem with the Na-dependent Cl/HCO exchanger, NDCBE, to mediate net NaCl absorption. Pendrin is stimulated by angiotensin II and aldosterone administration via the angiotensin type 1a and the mineralocorticoid receptors, respectively. It is also stimulated in models of metabolic alkalosis, such as with NaHCO administration. In some rodent models, pendrin-mediated HCO secretion modulates acid-base balance. However, of probably more physiological or clinical significance is the role of these pendrin-positive ICs in blood pressure regulation, which occurs, at least in part, through pendrin-mediated renal Cl absorption, as well as their effect on the epithelial Na channel, ENaC. Aldosterone stimulates ENaC directly through principal cell mineralocorticoid hormone receptor (ligand) binding and also indirectly through its effect on pendrin expression and function. In so doing, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. In addition to its role in Na and Cl balance, pendrin affects the balance of other ions, such as K and I. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contribution of pendrin-positive ICs in the kidney to distal nephron function and blood pressure.
Topics: Acid-Base Equilibrium; Aldosterone; Angiotensin II; Animals; Gene Expression Regulation; Humans; Kidney; Sulfate Transporters
PubMed: 32347156
DOI: 10.1152/physrev.00011.2019 -
Sisli Etfal Hastanesi Tip Bulteni 2020Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, and PGLs arise... (Review)
Review
Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, and PGLs arise from chromaffin cells in the ganglia of the autonomic nervous system. Paragangliomas originate from sympathetic or parasympathetic ganglia in the abdomen, thorax, and pelvis. The majority of PCC and sympathetic PGL are endocrine active tumors causing clinical symptoms by secreting excess catecholamines (norepinephrine, epinephrine, dopamine) and their metabolites. The incidence of PCC and PGL ranges between 2 and 8 per million, with a prevalence between 1:2500 and 1:6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatric patients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between 2-4.5% in the pediatric age group. 10-49% of these tumors is detected incidentally in imaging techniques performed for other reasons. However, 4-8% of adrenal incidentalomas are PCCs. Of these neuroendocrine tumors, 80-85% are PCCs and 15-20% are PGLs. Up to 40% of patients with PCC and PGL has disease-specific germline mutations and the situation is hereditary. Of 60% of the remaining sporadic patients, at least 1/3 has a somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditary cases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. Although PCCs and PGLs have scoring systems for histological evaluation of the primary tumor, it is not possible to diagnose whether the tumor is malignant since there is no histological system approved for the biological aggressiveness of this tumor group. Metastasis is defined as the presence of chromaffin tissue in non-chromaffin organs, such as lymph nodes, liver, lungs and bone. Although most of the PCC and PGL are benign, the metastatic disease may develop in 15-17%. Metastatic disease is reported between 2-25% in PCCs and 2.4-60% in PGLs. The TNM staging system of the American Joint Committee on Cancer (AJCC) was developed to predict the prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.
PubMed: 32617052
DOI: 10.14744/SEMB.2020.18794 -
Endocrine-related Cancer Jan 2023Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis.... (Review)
Review
Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets.
Topics: Humans; DNA, Mitochondrial
PubMed: 36219865
DOI: 10.1530/ERC-22-0217 -
Endocrine Pathology Jun 2021Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although... (Review)
Review
Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although few pathologists outside of endocrine tertiary centers will ever diagnose such a lesion, the tumors are well known through the medical community-possible due to a combination of the sheer rarity, their often-spectacular presentation due to excess catecholamine secretion as well as their unrivaled coupling to constitutional susceptibility gene mutations and hereditary syndromes. All PPGLs are thought to harbor malignant potential, and therefore pose several challenges to the practicing pathologist. Specifically, a responsible diagnostician should recognize both the capacity and limitations of histological, immunohistochemical, and molecular algorithms to pinpoint high risk for future metastatic disease. This focused review aims to provide the surgical pathologist with a condensed update regarding the current strategies available in order to deliver an accurate prognostication of these enigmatic lesions.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Humans; Immunohistochemistry; Paraganglioma; Pathology, Molecular; Pheochromocytoma
PubMed: 33768452
DOI: 10.1007/s12022-021-09675-0