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Endocrine Journal Jan 2024Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These tumors secrete adrenaline and noradrenaline, but paragangliomas usually produce only noradrenaline because of the lack of phenylethanolamine N-methyltransferase (PNMT) expression. Composite paragangliomas, which are complex tumors consisting of multiple types of neuroblastic cells, are extremely rare. We present the case of a 46-year-old woman with an atypical catecholamine profile who was preoperatively diagnosed with pheochromocytoma. However, postoperative pathology revealed that the patient had an extra-adrenal paraganglioma accompanied by a ganglioneuroma, which led to the diagnosis of a composite tumor. Interestingly, PNMT is expressed in both paragangliomas and ganglioneuromas. In addition, we reviewed reported composite paragangliomas and compared their clinical features with those of composite pheochromocytomas. We also discuss various aspects of the etiology of composite paragangliomas and the mechanism by which PNMT is expressed in tumors.
Topics: Female; Humans; Middle Aged; Catecholamines; Pheochromocytoma; Ganglioneuroma; Phenylethanolamine N-Methyltransferase; Paraganglioma; Adrenal Gland Neoplasms; Norepinephrine
PubMed: 37952980
DOI: 10.1507/endocrj.EJ23-0271 -
Biochemical Pharmacology Dec 2023Angiotensin II (AngII), as an octapeptide hormone normally ionized at physiological pH, cannot cross cell membranes and thus, relies on, two (mainly) G protein-coupled... (Review)
Review
Angiotensin II (AngII), as an octapeptide hormone normally ionized at physiological pH, cannot cross cell membranes and thus, relies on, two (mainly) G protein-coupled receptor (GPCR) types, ATR and ATR, to exert its intracellular effects in various organ systems including the cardiovascular one. Although a lot remains to be elucidated about the signaling of the ATR, ATR signaling is known to be remarkably versatile, mobilizing a variety of G protein-dependent and independent signal transduction pathways inside cells to produce a biological outcome. Cardiac ATR signaling leads to hypertrophy, adverse remodeling, fibrosis, while vascular ATR signaling raises blood pressure via vasoconstriction, but also elicits hypertrophic, vascular growth/proliferation, and pathological remodeling sets of events. In addition, adrenal ATR is the major physiological stimulus (alongside hyperkalemia) for secretion of aldosterone, a mineralocorticoid hormone that contributes to hypertension, electrolyte abnormalities, and to pathological remodeling of the failing heart. Regulator of G protein Signaling (RGS) proteins, discovered about 25 years ago as GTPase-activating proteins (GAPs) for the Gα subunits of heterotrimeric G proteins, play a central role in silencing G protein signaling from a plethora of GPCRs, including the AngII receptors. Given the importance of AngII and its receptors, but also of several RGS proteins, in cardiovascular homeostasis, the physiological and pathological significance of RGS protein-mediated modulation of cardiovascular AngII signaling comes as no surprise. In the present review, we provide an overview of the current literature on the involvement of RGS proteins in cardiovascular AngII signaling, by discussing their roles in cardiac (cardiomyocyte and cardiofibroblast), vascular (smooth muscle and endothelial cell), and adrenal (medulla and cortex) AngII signaling, separately. Along the way, we also highlight the therapeutic potential of enhancement of, or, in some cases, inhibition of each RGS protein involved in AngII signaling in each one of these cell types.
Topics: Humans; Angiotensin II; Cardiovascular System; GTP-Binding Proteins; Hypertrophy; Receptor, Angiotensin, Type 1; RGS Proteins; Signal Transduction
PubMed: 37922976
DOI: 10.1016/j.bcp.2023.115904 -
Therapeutic Advances in Endocrinology... 2023This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40-60% of... (Review)
Review
This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40-60% of tumors are linked to a known mutation. Tumor DNA should be sampled first. Next-generation sequencing is the best and most cost-effective choice and also helps with the expansion of current knowledge. Recent advancements have also led to the increased incorporation of regulatory RNA, metabolome markers, and the NETest in PPGL workup. PPGL presentation is highly volatile and nonspecific due to its multifactorial etiology. Symptoms mainly derive from catecholamine (CMN) excess or mass effect, primarily affecting the cardiovascular system. However, paroxysmal nature, hypertension, and the classic triad are no longer perceived as telltale signs. Identifying high-risk subjects and diagnosing patients at the correct time by using appropriate personalized methods are essential. Free plasma/urine catecholamine metabolites must be first-line examinations using liquid chromatography with tandem mass spectrometry as the gold standard analytical method. Reference intervals should be personalized according to demographics and comorbidity. The same applies to result interpretation. Threefold increase from the upper limit is highly suggestive of PPGL. Computed tomography (CT) is preferred for pheochromocytoma due to better cost-effectiveness and spatial resolution. Unenhanced attenuation of >10HU in non-contrast CT is indicative. The choice of extra-adrenal tumor imaging is based on location. Functional imaging with positron emission tomography/computed tomography and radionuclide administration improves diagnostic accuracy, especially in extra-adrenal/malignant or familial cases. Surgery is the mainstay treatment when feasible. Preoperative α-adrenergic blockade reduces surgical morbidity. Aggressive metastatic PPGL benefits from systemic chemotherapy, while milder cases can be managed with radionuclides. Short-term postoperative follow-up evaluates the adequacy of resection. Long-term follow-up assesses the risk of recurrence or metastasis. Asymptomatic carriers and their families can benefit from surveillance, with intervals depending on the specific gene mutation. Trials primarily focusing on targeted therapy and radionuclides are currently active. A multidisciplinary approach, correct timing, and personalization are key for successful PPGL management.
PubMed: 37916027
DOI: 10.1177/20420188231207544 -
JCEM Case Reports May 2023Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine...
Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors of the adrenal medulla chromaffin cells, usually associated with features of catecholamine excess. Clinically and biochemically silent pheochromocytoma without adrenergic symptoms or elevated catecholamine concentrations are rare. A 71-year-old female presented with acute right flank pain with abdominal computed tomography (CT) scan revealing a hemorrhagic right adrenal mass. She had no preceding adrenergic symptoms, and normal serum electrolytes, on a background of well-controlled hypertension on amlodipine monotherapy. After conservative management and discharge, an outpatient CT adrenal scan confirmed an 88 × 64 mm right adrenal mass demonstrating intense avidity (maximum standardized uptake value, 20.2) on fluorodeoxyglucose F 18-positron emission tomography (FDG-PET)/CT scan. Biochemical screening supported a nonfunctional adrenal lesion with normal-range plasma normetanephrines and metanephrines. She underwent a right adrenalectomy for presumed nonfunctioning adrenocortical cancer; however, histopathology demonstrated a 120-mm pheochromocytoma. Succinate dehydrogenase subunit B (SDHB) and fumarate hydratase (FH) staining were retained; however, weakly positive 2SC staining raised concerns for FH-deficient pheochromocytoma. Germline DNA sequencing was negative for pathogenic RET, VHL, SDHB, SDHD, or FH variants. Tumor cells stained positive for tyrosine hydroxylase and negative for dopamine β hydroxylase. Four months postoperatively, progress FDG-PET/CT scan demonstrated no focal avidity. Massive biochemically silent pheochromocytomas are exceedingly rare, and we discuss various mechanisms that may predispose patients to this phenomenon.
PubMed: 37908587
DOI: 10.1210/jcemcr/luad061 -
JCEM Case Reports May 2023Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10 cm,...
Pheochromocytomas are neuroendocrine tumors that arise from chromaffin cells in the adrenal medulla. Giant pheochromocytomas commonly measure greater than 7 to 10 cm, and their incidence and presentation is not well known. We present a case of a 62-year-old female with a giant 15.9 cm cystic pheochromocytoma. The patient was medically managed with oral phenoxybenzamine solution dose 4 times greater than average and was treated with a radical left nephrectomy and adrenalectomy. This case offers insight into the clinical presentation of giant pheochromocytomas and the unique challenges they present both medically and surgically.
PubMed: 37908578
DOI: 10.1210/jcemcr/luad065 -
Cureus Sep 2023We report a rare case of a solitary paraganglioma arising from the small bowel mesentery, found in a 70-year-old female who presented with abdominal pain. Paragangliomas...
We report a rare case of a solitary paraganglioma arising from the small bowel mesentery, found in a 70-year-old female who presented with abdominal pain. Paragangliomas are rare neuroendocrine, neural crest-derived tumors, most commonly found in the adrenal medulla. While extra-adrenal paragangliomas arise from diverse locations, mesenteric origins are extremely rare. Our comprehensive review shows 35 previously documented cases and updates the epidemiology, clinical features, and outcomes of mesenteric paragangliomas.
PubMed: 37868495
DOI: 10.7759/cureus.45685 -
Annals of Cardiac Anaesthesia 2023Pheochromocytomas are catecholamine-secreting tumours arising mostly from the adrenal medulla. With the advancement in surgical and anaesthetic techniques, the incidence...
Pheochromocytomas are catecholamine-secreting tumours arising mostly from the adrenal medulla. With the advancement in surgical and anaesthetic techniques, the incidence of severe morbidity and mortality associated with surgery is low. However, concurrent coronary artery disease and pheochromocytoma continue to be a challenge due to the risk of adverse cardiovascular events. We describe the successful management of pheochromocytoma excision in a patient with coronary artery disease.
Topics: Humans; Pheochromocytoma; Coronary Artery Disease; Adrenalectomy; Adrenal Gland Neoplasms; Anesthesia; Laparoscopy
PubMed: 37861585
DOI: 10.4103/aca.aca_14_23 -
Pflugers Archiv : European Journal of... Jan 2024
Topics: Calcium; Chromaffin Cells; Adrenal Glands; Adrenal Medulla; Catecholamines
PubMed: 37843577
DOI: 10.1007/s00424-023-02867-z -
International Journal of Molecular... Sep 2023Chronic stress is known to perturb serotonergic regulation in the brain, leading to mood, learning and memory impairments and increasing the risk of developing mood...
Chronic stress is known to perturb serotonergic regulation in the brain, leading to mood, learning and memory impairments and increasing the risk of developing mood disorders. The influence of the gut microbiota on serotonergic regulation in the brain has received increased attention recently, justifying the investigation of the role of diet on the gut and the brain in mood disorders. Here, using a 4-week chronic unpredictable mild stress (CUMS) model in mice, we aimed to investigate the effects of a high-fat high-glycaemic index (HFD) and high-fibre fruit & vegetable "superfood" (SUP) modifications of a semi-pure AIN93M diet on behaviour, serotonin synthesis and metabolism pathway regulation in the brain and the gut, as well as the gut microbiota and the peripheral adrenal medullary system. CUMS induced anxiety-like behaviour, dysregulated the tryptophan and serotonin metabolic pathways in the hippocampus, prefrontal cortex, and colon, and altered the composition of the gut microbiota. CUMS reduced the catecholamine synthetic capacity of the adrenal glands. Differential effects were found in these parameters in the HFD and SUP diet. Thus, dietary modifications may profoundly affect the multiple dynamic systems involved in mood disorders.
Topics: Mice; Animals; Serotonin; Mice, Inbred C57BL; Brain; Diet; Adrenal Medulla; Stress, Psychological; Depression
PubMed: 37834073
DOI: 10.3390/ijms241914618 -
Frontiers in Oncology 2023Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic... (Review)
Review
Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT.
PubMed: 37823059
DOI: 10.3389/fonc.2023.1254322