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Frontiers in Endocrinology 2023Pheochromocytomas and Paragangliomas (Pheo/PGL) are rare catecholamine-producing tumours derived from adrenal medulla or from the extra-adrenal paraganglia respectively.... (Review)
Review
Pheochromocytomas and Paragangliomas (Pheo/PGL) are rare catecholamine-producing tumours derived from adrenal medulla or from the extra-adrenal paraganglia respectively. Around 10-15% of Pheo/PGL develop metastatic forms and have a poor prognosis with a 37% of mortality rate at 5 years. These tumours have a strong genetic determinism, and the presence of succinate dehydrogenase B (SDHB) mutations are highly associated with metastatic forms. To date, no effective treatment is present for metastatic forms. In addition to cancer cells, the tumour microenvironment (TME) is also composed of non-neoplastic cells and non-cellular components, which are essential for tumour initiation and progression in multiple cancers, including Pheo/PGL. This review, for the first time, provides an overview of the roles of TME cells such as cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) on Pheo/PGL growth and progression. Moreover, the functions of the non-cellular components of the TME, among which the most representatives are growth factors, extracellular vesicles and extracellular matrix (ECM) are explored. The importance of succinate as an oncometabolite is emerging and since Pheo/PGL SDH mutated accumulate high levels of succinate, the role of succinate and of its receptor (SUCNR1) in the modulation of the carcinogenesis process is also analysed. Further understanding of the mechanism behind the complicated effects of TME on Pheo/PGL growth and spread could suggest novel therapeutic targets for further clinical treatments.
Topics: Humans; Pheochromocytoma; Tumor Microenvironment; Paraganglioma; Adrenal Gland Neoplasms; Succinates
PubMed: 37033265
DOI: 10.3389/fendo.2023.1137456 -
Sisli Etfal Hastanesi Tip Bulteni 2020Indications for adrenalectomy are malignancy suspicion or malignant tumors, non-functional tumors with the risk of malignancy and functional adrenal tumors. Regardless... (Review)
Review
Indications for adrenalectomy are malignancy suspicion or malignant tumors, non-functional tumors with the risk of malignancy and functional adrenal tumors. Regardless of the size of functional tumors, they have surgical indications. The hormone-secreting adrenal tumors in which adrenalectomy is indicated are as follows: Cushing's syndrome, arises from hypersecretion of glucocorticoids produced in fasciculata adrenal cortex, Conn's syndrome, arises from an hypersecretion of aldosterone produced by glomerulosa adrenal cortex, and Pheochromocytomas that arise from adrenal medulla and produce catecholamines. Sometimes, bilateral adrenalectomy may be required in Cushing's disease due to pituitary or ectopic ACTH secretion. Adenomas arise from the reticularis layer of the adrenal cortex, which rarely releases too much adrenal androgen and estrogen, may also develop and have an indication for adrenalectomy. Adrenal surgery can be performed by laparoscopic or open technique. Today, laparoscopic adrenalectomy is the gold standard treatment in selected patients. Laparoscopic adrenalectomy can be performed transperitoneally or retroperitoneoscopically. Both approaches have their advantages and disadvantages. In the selection of the surgery type, the experience and habits of the surgeon are also important, along with the patient's characteristics. The most common type of surgery performed in the world is laparoscopic transabdominal lateral adrenalectomy, which most surgeons are more familiar with. The laparoscopic anterior transperitoneal approach is the least preferred laparoscopic method in adrenalectomy. Retroperitoneal laparoscopic adrenalectomy can be performed with a posterior or lateral approach. In addition to conventional laparoscopy, laparoscopic surgery is robot-assisted, which can be administered by transperitoneal or retroperitoneal approach. In addition, conventional or robot-assisted laparoscopic adrenalectomy can be performed transabdominally or retroperitoneally using the single-port method. Today, partial adrenalectomy can be performed using laparoscopic techniques in bilateral adrenal masses, hereditary diseases with the risk of developing multiple adrenal tumors, and solitary masses of the adrenal gland. Open surgery is indicated in the case of malignancy or suspected malignancy and large tumors when laparoscopic surgery is contraindicated. The risk of conversion to open surgery is low (approximately 5%). The open transperitoneal anterior approach is the most common open intervention, especially in large tumors with malignancy or suspected malignancy. This procedure can be performed using a midline incision, bilateral or unilateral subcostal incision, Makuuchi or modified Makuuchi incision. Thoracoabdominal incision may be required, especially in the removal of large malignant lesions as a block. The open retroperitoneal approach can be applied posteriorly or laterally.
PubMed: 32377128
DOI: 10.14744/SEMB.2019.05578 -
Experimental and Therapeutic Medicine Nov 2021Ganglioneuroma, a rare neural crest-derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma).... (Review)
Review
Ganglioneuroma, a rare neural crest-derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma). Ganglioneuromas can be found anywhere autonomic ganglia are located, mostly abdominal/pelvic sites followed by the adrenal glands (one-third of cases), mediastinum/thorax and cervical area. Affecting especially children more than 10 years of age, Ganglioneuroma is either asymptomatic or may cause local compressive effects; rarely inducing nonspecific abdominal complains or arterial hypertension related to oversecretion of epinephrine/norepinephrine/dopamine. Despite a good prognosis, adrenalectomy is necessary in order to rule out a malignancy. Open procedure represents the standard therapeutic option; alternatively, centers with large laparoscopic pediatric experience and good stratification protocols have reported successful procedures. High uptake of I-MIBG is associated with a more severe outcome in cases with increased mitotic index. In neuroblastic tumors, neuron-specific enolase >33 ng/ml, age at diagnosis <49 months, and blood vessel invasion indicate a poor prognosis. Concurrent extra-adrenal/adrenal ganglioneuroma is associated with a more severe prognosis; post-surgical complications are more frequent in non-adrenal vs. adrenal ganglioneuroma. Exceptionally, immune-mediated paraneoplastic neurologic syndromes have been reported: anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus-myoclonus-ataxia syndrome. ROHHAD syndrome is the underlying cause in 40-56% of cases of neuroendocrine tumors including ganglioneuroma; 70% of tumors are diagnosed within the first 24 months after hypothalamic obesity onset, associated with a severe prognosis due to hypoventilation, sleep apnea, and dysautonomia. Recently, the PKB/AKT/mTOR/S6 pathway was identified as a tumorigenic pathway in pediatric ganglioneuroma, not in neuroblastoma; mTOR inhibitors are a potential option for pre-operatory tumor shrinkage. Pediatric adrenal ganglioneuroma has a good prognosis if adequately treated; its recognition requires adrenalectomy. Further development of specific biomarkers is needed. In the present article, we aimed to introduce a review of the literature involving adrenal ganglioneuroma based on a practical, multidisciplinary perspective of prognostic factors.
PubMed: 34630692
DOI: 10.3892/etm.2021.10773 -
Life (Basel, Switzerland) Oct 2022Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth... (Review)
Review
Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth understanding of the underlying mechanisms. Sympathetic activation has long been known to play a key role in the pathophysiology of ischemia-induced arrhythmias, but the regulating factors remain under investigation. Several lines of evidence implicate the endothelin system (a family of three isopeptides and two specific receptors) as an important modulator of sympathetic activation in the setting of acute coronary syndromes. Such interaction is present in the heart and in the adrenal medulla, whereas less is known on the effects of the endothelin system on the central autonomic network. This article summarizes the current state-of-the-art, placing emphasis on early-phase arrhythmogenesis, and highlights potential areas of future research.
PubMed: 36295062
DOI: 10.3390/life12101627 -
Cancer Medicine Jul 2023Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they... (Review)
Review
Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.
Topics: Humans; Pheochromocytoma; Paraganglioma; Carcinogenesis; Cell Transformation, Neoplastic; Adrenal Gland Neoplasms
PubMed: 37145019
DOI: 10.1002/cam4.6010 -
Current Problems in Diagnostic Radiology 2019Adrenal tumors are very commonly encountered in the practice of radiology. They may arise from the adrenal gland itself, either the cortex or the medulla, or they could... (Review)
Review
Adrenal tumors are very commonly encountered in the practice of radiology. They may arise from the adrenal gland itself, either the cortex or the medulla, or they could be secondary lesions. They may be benign or malignant. The functioning adrenal tumors lead to hypersecretion of adrenal hormones leading to clinical syndromes. Computed tomography is the most common imaging modality used for the initial evaluation of adrenal tumors. Magnetic resonance imaging and functional scintigraphic techniques are frequently used for atypical presentations or further evaluation. We present a multimodality review of common and uncommon adrenal tumors. We highlight their characteristic and specific imaging features which help us in making a diagnosis and suggesting an appropriate follow up for further management. The spectrum of adrenal tumors is wide with varying appearances on different imaging modalities. Imaging techniques used for adrenal tumor imaging have their own strengths and weaknesses as it relates to the final diagnosis. It is important to be familiar with imaging characteristics of adrenal tumors for appropriate diagnosis and management. Differentiation of benign (leave alone) tumors from malignant (surgical) ones along with appropriate disposition of incidentalomas are some of the challenges facing the radiologist.
Topics: Adrenal Gland Neoplasms; Diagnosis, Differential; Humans; Incidental Findings; Multimodal Imaging
PubMed: 30472137
DOI: 10.1067/j.cpradiol.2018.10.002 -
Reviews in Endocrine & Metabolic... Feb 2023Diagnosis of pheochromocytoma or paraganglioma (PPGL) in pregnancy has been associated historically with high rates of materno-fetal morbidity and mortality. Recent... (Review)
Review
Diagnosis of pheochromocytoma or paraganglioma (PPGL) in pregnancy has been associated historically with high rates of materno-fetal morbidity and mortality. Recent evidence suggests outcomes are improved by recognition of PPGL before or during pregnancy and appropriate medical management with alpha-blockade. Whether antepartum surgery (before the third trimester) is required remains controversial and open to case-based merits. Women with PPGL in pregnancy are more commonly delivered by Caesarean section, although vaginal delivery appears to be safe in selected cases. At least some PPGLs express the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) which may explain their dramatic manifestation in pregnancy. PPGLs in pregnancy are often associated with heritable syndromes, and genetic counselling and testing should be offered routinely in this setting. Since optimal outcomes are only achieved by early recognition of PPGL in (or ideally before) pregnancy, it is incumbent for clinicians to be aware of this diagnosis in a pregnant woman with hypertension occurring before 20 weeks' gestation, and acute and/or refractory hypertension particularly if paroxysmal and accompanied by sweating, palpitations and/or headaches. All women with a past history of PPGL and/or heritable PPGL syndrome should be carefully assessed for the presence of residual or recurrent disease before considering pregnancy.
Topics: Pregnancy; Humans; Female; Pheochromocytoma; Cesarean Section; Paraganglioma; Adrenal Gland Neoplasms; Hypertension
PubMed: 36637675
DOI: 10.1007/s11154-022-09773-2 -
Neuroimmunomodulation 2023Bioelectronic medicine is a novel field in modern medicine based on the specific neuronal stimulation to control organ function, cardiovascular, and immune homeostasis.... (Review)
Review
Bioelectronic medicine is a novel field in modern medicine based on the specific neuronal stimulation to control organ function, cardiovascular, and immune homeostasis. However, most studies addressing neuromodulation of the immune system have been conducted on anesthetized animals, which can affect the nervous system and neuromodulation. Here, we review recent studies involving conscious experimental rodents (rats and mice) to better understand the functional organization of neural control of immune homeostasis. We highlight typical experimental models of cardiovascular regulation, such as electrical activation of the aortic depressor nerve or the carotid sinus nerve, bilateral carotid occlusion, the Bezold-Jarisch reflex, and intravenous administration of the bacterial endotoxin lipopolysaccharide. These models have been used to investigate the relationship between neuromodulation of the cardiovascular and immune systems in conscious rodents (rats and mice). These studies provide critical information about the neuromodulation of the immune system, particularly the role of the autonomic nervous system, i.e., the sympathetic and parasympathetic branches acting both centrally (hypothalamus, nucleus ambiguus, nucleus tractus solitarius, caudal ventrolateral medulla, and rostral ventrolateral medulla), and peripherally (particularly spleen and adrenal medulla). Overall, the studies in conscious experimental models have certainly highlighted to the reader how the methodological approaches used to investigate cardiovascular reflexes in conscious rodents (rats and mice) can also be valuable for investigating the neural mechanisms involved in inflammatory responses. The reviewed studies have clinical implications for future therapeutic approaches of bioelectronic modulation of the nervous system to control organ function and physiological homeostasis in conscious physiology.
Topics: Rats; Mice; Animals; Solitary Nucleus; Inflammation; Neurons; Autonomic Nervous System; Hypothalamus; Sympathetic Nervous System; Heart Rate; Blood Pressure
PubMed: 37232031
DOI: 10.1159/000530908 -
Endocrine Oncology (Bristol, England) Jan 2022Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately 15-25% of PCC/PGL can become metastatic. Up to 30-40% of patients with PCC/PGL have a germline pathogenic variant in a known susceptibility gene for PCC/PGL; therefore, all patients with PCC/PGL should undergo clinical genetic testing. Most of the susceptibility genes are associated with variable penetrance for PCC/PGL and are associated with different syndromes, which include susceptibility for other tumors and conditions. The objective of this review is to provide an overview of the germline susceptibility genes for PCC/PGL, the associated clinical syndromes, and recommended surveillance.
PubMed: 37435466
DOI: 10.1530/EO-22-0044 -
Journal of the Endocrine Society Feb 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia,... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the highest degree of heritability among endocrine tumors. Currently, ~40% of individuals with PPGLs have a genetic germline and there are at least 12 different genetic syndromes related to these tumors. Metastatic PPGLs are defined by the presence of distant metastases at sites where chromaffin cells are physiologically absent. Approximately 10% of pheochromocytomas and ~40% of sympathetic paragangliomas are linked to metastases, explaining why complete surgical resection is the first-choice treatment for all PPGL patients. The surgical approach is a high-risk procedure requiring perioperative management by a specialized multidisciplinary team in centers with broad expertise. In this review, we summarize and discuss the most relevant aspects of perioperative management in patients with pheochromocytomas and sympathetic paragangliomas.
PubMed: 35128297
DOI: 10.1210/jendso/bvac004