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The Journal of Clinical Endocrinology... May 2018Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from... (Review)
Review
CONTEXT
Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize; there are no known cures for metastasized PGLs.
METHODS
Original articles and reviews indexed in PubMed were identified by querying with specific PCC/PGL- and Krebs cycle pathway-related terms. Additional references were selected through the in-depth analysis of the relevant publications.
RESULTS
We primarily discuss Krebs cycle mutations that can be instrumental in helping investigators identify key biological pathways and molecules that may serve as biomarkers of or treatment targets for PCC/PGL.
CONCLUSION
The mainstay of treatment of patients with PCC/PGLs is surgical. However, the tide may be turning with the discovery of new genes associated with PCC/PGLs that may shed light on oncometabolites used by these tumors.
Topics: Adrenal Gland Neoplasms; Cell Transformation, Neoplastic; Energy Metabolism; Humans; Paraganglioma; Pheochromocytoma
PubMed: 29409060
DOI: 10.1210/jc.2017-01991 -
Updates in Surgery Jun 2017Adrenal tumors can vary from a benign adrenocortical adenoma with no hormonal secretion to a secretory adrenocortical malignancy (adrenocortical carcinoma) or a... (Review)
Review
Adrenal tumors can vary from a benign adrenocortical adenoma with no hormonal secretion to a secretory adrenocortical malignancy (adrenocortical carcinoma) or a hormone-secreting tumor of the adrenal medulla (pheochromocytoma). Currently, laparoscopic adrenalectomy is regarded as the preferred surgical approach for the management of most adrenal surgical disorders, although there are no prospective randomized trials comparing this technique with open adrenalectomy. However, widespread adoption of robotic technology has positioned robotic adrenalectomy as an option in some medical centers. Speculative advantages associated with the use of the robotic system have rarely been evaluated in clinical settings and cost increase remains an important drawback associated with robotic surgery. This review summarizes current available data regarding robotic transperitoneal adrenalectomy including its indications, advantages, limitations, and comparison with conventional laparoscopic adrenalectomy. We believe that the use of a robotic system seems to be useful especially in more difficult patients with larger tumors, truncal paragangliomas, and bilateral and/or partial adrenalectomies. Overall, we believe that overcosts due to robotic system use could be balanced by hospital stay decrease, patients' referral increase, improved postoperative outcomes in more difficult patients and ergonomics for the surgeon. However, we also believe that the current surgical intuitive business model is counterproductive, because there are no available strong clinical data that could balance overcosts associated with the use of the robotic system.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Humans; Laparoscopy; Robotic Surgical Procedures
PubMed: 28497219
DOI: 10.1007/s13304-017-0448-6 -
Frontiers in Endocrinology 2022The adrenal medulla plays a critical role in mammalian homeostasis and the stress response. It is populated by clustered chromaffin cells that secrete epinephrine or...
The adrenal medulla plays a critical role in mammalian homeostasis and the stress response. It is populated by clustered chromaffin cells that secrete epinephrine or norepinephrine along with peptides into the bloodstream affecting distant target organs. Despite been heavily studied, the central control of adrenal medulla and spatiotemporal responsiveness remains poorly understood. For this work, we continuously monitored the electrical activity of individual adrenomedullary chromaffin cells in the living anesthetized rat using multielectrode arrays. We measured the chromaffin cell activity under basal and physiological stress conditions and characterized the functional micro-architecture of the adrenal medulla. Under basal conditions, chromaffin cells fired action potentials with frequencies between ~0.2 and 4 Hz. Activity was almost completely driven by sympathetic inputs coming through the splanchnic nerve. Chromaffin cells were organized into independent local networks in which cells fired in a specific order, with latencies from hundreds of microseconds to a few milliseconds. Electrical stimulation of the splanchnic nerve evoked almost exactly the same spatiotemporal firing patterns that occurred spontaneously. Hypoglycemic stress, induced by insulin administration resulted in increased activity of a subset of the chromaffin cells. In contrast, respiratory arrest induced by lethal anesthesia resulted in an increase in the activity of virtually all chromaffin cells before cessation of all activity. These results suggest a stressor-specific activation of adrenomedullary chromaffin cell networks and revealed a surprisingly complex electrical organization that likely reflects the dynamic nature of the adrenal medulla's neuroendocrine output during basal conditions and during different types of physiological stress.
Topics: Adrenal Medulla; Animals; Chromaffin Cells; Epinephrine; Mammals; Norepinephrine; Rats; Splanchnic Nerves
PubMed: 35795145
DOI: 10.3389/fendo.2022.875865 -
Clinics (Sao Paulo, Brazil) Dec 2018Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare... (Review)
Review
Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.
Topics: Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Antineoplastic Agents, Hormonal; Humans; Mitotane; Paraganglioma; Pheochromocytoma
PubMed: 30540124
DOI: 10.6061/clinics/2018/e756s -
Frontiers in Endocrinology 2018The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress... (Review)
Review
The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Catecholamines released from the adrenal medulla function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. The immune system has an active role in the progression of hypertension and cytokines are powerful modulators of adrenal cell function. Adrenal medullary cells integrate neural, hormonal, and immune signals. Changes in adrenal cytokines during the progression of hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis. This review highlights the potential interactions of cytokine signaling networks with those of catecholamine biosynthesis within the adrenal, and discusses the role of cytokines in the coordination of blood pressure regulation and the stress response.
PubMed: 30013513
DOI: 10.3389/fendo.2018.00343 -
Cellular and Molecular Neurobiology Jan 2021Nicotinic acetylcholine receptors (nAChRs) have gained much attention in the scientific community since they play a significant role in multiple physiological and... (Review)
Review
Nicotinic acetylcholine receptors (nAChRs) have gained much attention in the scientific community since they play a significant role in multiple physiological and pathophysiological processes. Multiple approaches to study the receptors exist, with characterization of the receptors' functionality at a single cellular level using cell culturing being one of them. Derived from an adrenal medulla tumor, PC12 cells express nicotinic receptor subunits and form functional nicotinic receptors. Thus, the cells offer a convenient environment to address questions related to the functionality of the receptors. The review summarizes the findings on nicotinic receptors' expression and functions which were conducted using PC12 cells. Specific focus is given to α3-containing receptors as well as α7 receptor. Critical evaluation of findings is provided alongside insights into what can still be learned about nAChRs, using PC12 cells.
Topics: Animals; Models, Biological; PC12 Cells; Protein Subunits; Rats; Receptors, Nicotinic
PubMed: 32335772
DOI: 10.1007/s10571-020-00846-x -
Cancer Prevention Research... Feb 2020From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief... (Review)
Review
From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.
Topics: Administration, Inhalation; Disease Progression; Electronic Nicotine Delivery Systems; Heating; Humans; Neoplasms; Nicotine; Risk Factors; Smoking; Smoking Cessation; Sympathoadrenal System; Tobacco Products
PubMed: 31619443
DOI: 10.1158/1940-6207.CAPR-19-0346 -
Cureus Nov 2022Pheochromocytomas are rare tumors located in the adrenal medulla, that derives from the chromaffin cells and produce catecholamines. They are an uncommon cause of...
Pheochromocytomas are rare tumors located in the adrenal medulla, that derives from the chromaffin cells and produce catecholamines. They are an uncommon cause of hypertension, and only 50% of the patients present symptoms compatible with this pathology. Here we describe the case of a 70-year-old woman with a history of anxiety, hypertension and palpitation, who had an unspecified nodule in the right adrenal gland. Laboratory studies revealed an elevated urinary metanephrines secretion. A diagnosis of pheochromocytoma was made and an adrenalectomy was performed. Our aim is to highlight the diagnosis of this rare tumor and how its early management can prevent morbidity and mortality.
PubMed: 36523722
DOI: 10.7759/cureus.31409 -
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