-
Endocrine-related Cancer Dec 2023The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually...
The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), the enzyme required for epinephrine production, which was explained by the absence of glucocorticoids. PGLs with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur in or outside of the adrenal, but always synthesize epinephrine independently of the localization. Here, we characterize the signaling pathways through which PVs in HRAS influence PNMT expression. Catecholamines, cortisol, and transcriptional features of PGL tissues with known genetic background were analyzed. Genetically modified rat pheochromocytoma cells carrying PVs in Hras were generated and analyzed for regulation of Pnmt expression. Elevated epinephrine contents in PGLs with PVs in HRAS were accompanied by enrichment in mitogen-activated protein kinase (MAPK) signaling compared to PGLs with PVs in genes that activate hypoxia pathways. In vitro, Hras PVs increased Pnmt expression and epinephrine biosynthesis through increased phosphorylation of stimulatory protein 1 via MAPK signaling. Here, we provide a molecular mechanism that explains the PV-dependent epinephrine production of PGLs.
Topics: Humans; Pheochromocytoma; Proto-Oncogene Proteins p21(ras); Adrenal Gland Neoplasms; Paraganglioma; Epinephrine
PubMed: 37902037
DOI: 10.1530/ERC-23-0230 -
Journal of Toxicology and Environmental... Aug 2023Carbon tetrachloride (CCl) has been extensively used and reported to produce toxicity, most notably involving the liver. Carbon tetrachloride metabolism involves... (Review)
Review
Carbon tetrachloride (CCl) has been extensively used and reported to produce toxicity, most notably involving the liver. Carbon tetrachloride metabolism involves CYP450-mediated bioactivation to trichloromethyl and trichloromethyl peroxy radicals, which are capable of macromolecular interaction with cell components including lipids and proteins. Radical interaction with lipids produces lipid peroxidation which can mediate cellular damage leading to cell death. Chronic exposure with CCl a rodent hepatic carcinogen with a mode of action (MOA) exhibits the following key events: 1) metabolic activation; 2) hepatocellular toxicity and cell death; 3) consequent regenerative increased cell proliferation; and 4) hepatocellular proliferative lesions (foci, adenomas, carcinomas). The induction of rodent hepatic tumors is dependent upon the dose (concentration and exposure duration) of CCl, with tumors only occurring at cytotoxic exposure levels. Adrenal benign pheochromocytomas were also increased in mice at high CCl exposures; however, these tumors are not of relevant importance to human cancer risk. Few epidemiology studies that have been performed on CCl, do not provide credible evidence of enhanced risk of occurrence of liver or adrenal cancers, but these studies have serious flaws limiting their usefulness for risk assessment. This manuscript summarizes the toxicity and carcinogenicity attributed to CCl, specifically addressing MOA, dose-response, and human relevance.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Liver Neoplasms; Pheochromocytoma; Adrenal Gland Neoplasms; Lipids
PubMed: 37282619
DOI: 10.1080/10937404.2023.2220147 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable... (Review)
Review
Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable tumors. Massive sequencing combined with careful patient selection has so far identified more than twenty susceptibility genes, leading to an over-detection of variants of unknown significance (VUS) that require precise molecular markers to determine their pathogenic role. Moreover, some PPGL patients remain undiagnosed, possibly due to mutations in regulatory regions of already known genes or mutations in undiscovered genes. Accurate classification of VUS and identification of new genes require well-defined clinical and molecular markers that allow effective genetic diagnosis of most PPGLs.
PubMed: 38908536
DOI: 10.1016/j.bbcan.2024.189141 -
Annales D'endocrinologie Aug 2023Thoracic and cervical paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest progenitors located outside the adrenal... (Review)
Review
Thoracic and cervical paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest progenitors located outside the adrenal gland. We describe our current protocol as a multidisciplinary team for the management of cervical and thoracic PGLs. Surgery is generally considered the treatment of choice as it offers the best chance for cure. For resection of thoracic PGLs, video-assisted thoracoscopic surgery (VATS) is the main surgical approach, while open thoracotomy is preferred in case of tumors > 6cm, lacking confirmation of a plane of separation with adjacent structures, or with technical difficulties during VATS. In cervical PGLs, the surgical approach should be individualized according to location, mainly based on the Glasscock-Jackson and the Fisch-Mattox classifications. Surgery is the treatment of choice for most cervical and thoracic PGLs, but radiotherapy or observation could be more suitable options in unresectable cervical and thoracic PGLs or when resection has been incomplete.
Topics: Humans; Paraganglioma; Neuroendocrine Tumors; Adrenal Glands
PubMed: 36334803
DOI: 10.1016/j.ando.2022.10.013 -
Acta Chirurgica Belgica Oct 2023Pheochromocytoma is a rare catecholamine-secreting tumor of neuroendocrine origin. It has a prevalence of <1% in adults with hypertension. In some cases, hypertension is...
BACKGROUND
Pheochromocytoma is a rare catecholamine-secreting tumor of neuroendocrine origin. It has a prevalence of <1% in adults with hypertension. In some cases, hypertension is associated with the classical triad of headache, sweating, and tachycardia. Cardiogenic shock due to stress-induced cardiomyopathy caused by catecholamine excess may rarely be the initial symptom of pheochromocytoma, mimicking Takotsubo Syndrome.
METHODS
We report the case of a 58-year-old female patient with pheochromocytoma-induced cardiogenic shock (PICS) in the early postoperative period after thyroidectomy.
RESULTS
PICS is caused by a catecholamine storm, which induces myocardial stress and cardiac dysfunction. In such cases, early management with mechanical circulatory assistance may be promptly considered, given the increased risk of mortality.
CONCLUSION
PICS is a rare and serious condition. Prompt diagnosis and adequate resuscitation measures are necessary to avoid high mortality.
Topics: Adult; Female; Humans; Middle Aged; Pheochromocytoma; Shock, Cardiogenic; Catecholamines; Adrenal Gland Neoplasms; Hypertension
PubMed: 35583372
DOI: 10.1080/00015458.2022.2079822 -
Problemy Endokrinologii Nov 2023This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The... (Review)
Review
This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The main component of preoperative preparation is the use of alpha-blockers. The need to prescribe them to all patients is increasingly disputed, especially for patients without severe hypertension. An increasing number of publications demonstrate positive results of treatment without the use of alpha-blockers, advocating an individual approach and the use of the drug according to certain indications. Minimally invasive endoscopic techniques of adrenalectomy have become widespread in surgical treatment. They are represented by laparoscopic and retroperitonescopic technic, including using their single-port modifications. The earliest possible intersection of the central vein in the past was considered the most important aspect of adrenalectomy for pheochromocytoma, currently, due to the development of surgical techniques and anesthesiological manuals, this has ceased to be a mandatory rule of successful surgery. Despite the significant influence of the intersection of this vessel on intraoperative hemodynamics, surgical tactics with its later intersection have their own justifications and do not lead to a deterioration in treatment results. The standard volume of surgical intervention for pheochromocytomas is total adrenalectomy, however, in the presence of hereditary syndromes, such as multiple endocrine neoplasia type 2 syndrome, neurofibomatosis type 1, von Hippel-Lindau syndrome, it is possible to perform cortical-sparing adrenalectomy.
Topics: Humans; Pheochromocytoma; von Hippel-Lindau Disease; Adrenal Gland Neoplasms; Multiple Endocrine Neoplasia Type 2a; Adrenalectomy; Syndrome
PubMed: 37968950
DOI: 10.14341/probl13283 -
Radiographics : a Review Publication of... Jul 2023The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal...
The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.
Topics: Humans; Pheochromocytoma; Tomography, X-Ray Computed; Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Adenoma; Cysts; Adrenal Cortex Neoplasms; Lipids
PubMed: 37347698
DOI: 10.1148/rg.220191 -
Radiology Case Reports Aug 2024A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is...
A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is important that paragangliomas are identified, as they must often be treated by surgical excision. IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a systemic inflammatory disease that results in the infiltration of IgG4-positive plasma cells in the retroperitoneum. Such fibrosis may adversely affect nearby organs and tissues. Here, we describe a case of combined paraganglioma and IgG4-RPF in a 47-year-old female patient. This case demonstrates the deleterious effect of these two conditions when they occur simultaneously.
PubMed: 38800075
DOI: 10.1016/j.radcr.2024.04.065 -
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 Journal of Clinical Endocrinology... Jan 2024Sexual dimorphism has direct consequences on the incidence and survival of cancer. Early and accurate diagnosis is crucial to improve prognosis. (Observational Study)
Observational Study
CONTEXT
Sexual dimorphism has direct consequences on the incidence and survival of cancer. Early and accurate diagnosis is crucial to improve prognosis.
OBJECTIVE
This work aimed to characterized the influence of sex and adrenal asymmetry on the emergence of adrenal tumors.
METHODS
We conducted a multicenter, observational study involving 8037 patients with adrenal tumors, including adrenocortical carcinoma (ACC), aldosterone-producing adenoma (APA), cortisol-secreting adrenocortical adenomas (CSAs), non-aldosterone-producing adrenal cortical adenoma (NAPACA), pheochromocytoma (PCC), and neuroblastoma (NB), and investigated tumor lateralization according to sex. Human adrenal tissues (n = 20) were analyzed with a multiomics approach that allows determination of gene expression, catecholamine, and steroid contents in a single sample. In addition, we performed a literature review of computed tomography and magnetic resonance imaging-based studies examining adrenal gland size.
RESULTS
ACC (n = 1858); CSA (n = 68), NAPACA (n = 2174), and PCC (n = 1824) were more common in females than in males (female-to-male ratio: 1.1:1-3.8:1), whereas NBs (n = 2320) and APAs (n = 228) were less prevalent in females (0.8:1). ACC, APA, CSA, NAPACA, and NB occurred more frequently in the left than in the right adrenal (left-to-right ratio: 1.1:1-1.8:1), whereas PCC arose more often in the right than in the left adrenal (0.8:1). In both sexes, the left adrenal was larger than the right adrenal; females have smaller adrenals than males.
CONCLUSION
Adrenal asymmetry in both sexes may be related to the pathogenesis of adrenal tumors and should be considered during the diagnosis of these tumors.
Topics: Female; Humans; Male; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocortical Adenoma; Adrenocortical Carcinoma; Aldosterone; Pheochromocytoma; Sex Characteristics
PubMed: 37647861
DOI: 10.1210/clinem/dgad515