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Problemy Endokrinologii Oct 2023Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and... (Review)
Review
Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and «non-metastatic». Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Risk Factors; Paraganglioma; Neoplasm Metastasis
PubMed: 38796759
DOI: 10.14341/probl13331 -
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 -
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 -
Cureus Sep 2023This report presents the case of a 45-year-old man with a history of episodic headaches, palpitations, and sweating for the past six months. His blood pressure on...
This report presents the case of a 45-year-old man with a history of episodic headaches, palpitations, and sweating for the past six months. His blood pressure on admission was 170/100 mmHg. The patient was diagnosed with pheochromocytoma confirmed by elevated levels of plasma catecholamines and metanephrines. CT imaging revealed a 3 cm mass in the left adrenal gland with evidence of local invasion into the surrounding tissues. The patient underwent a laparoscopic adrenalectomy and was discharged on the third postoperative day with normal blood pressure. Histopathological examination confirmed the diagnosis of pheochromocytoma. The patient was followed for six months postoperatively with the resolution of symptoms and no evidence of tumor recurrence on imaging. Recurrence involves complex environment-gene interactions that are poorly understood. The diagnosis of pheochromocytoma could take several weeks to several years mainly because the symptoms are nonspecific and episodic. Although sudden death is rare, the debilitations associated with pheochromocytoma are often multisystemic with cardiovascular, emotional, and metabolic components. This case report highlights the importance of early diagnosis, appropriate management, and follow-up for pheochromocytoma.
PubMed: 37727845
DOI: 10.7759/cureus.45490 -
Endocrine Reviews Feb 2024Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues or extra-adrenal...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues or extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can provide essential knowledge for the development of better therapeutic and tumor management strategies, especially for those with advanced and metastatic PPGLs. The first part of this review outlines the fundamental principles of the immune system and tumor microenvironment, and their role in cancer immunoediting, particularly emphasizing on PPGLs. We focus on how the unique pathophysiology of PPGLs, such as their high molecular, biochemical, and imaging heterogeneity and production of several oncometabolites, creates a tumor-specific microenvironment and immunologically "cold" tumors. Thereafter, we discuss recently published studies related to the reclustering of PPGLs based on their immune signature. The second part of this review discusses future perspectives in PPGL management, including immunodiagnostic and promising immunotherapeutic approaches for converting "cold" tumors into immunologically active or "hot" tumors known for their better immunotherapy response and patient outcomes. Special emphasis is placed on potent immune-related imaging strategies and immune signatures that could be used for the reclassification, prognostication, and management of these tumors to improve patient care and prognosis. Furthermore, we introduce currently available immunotherapies and their possible combinations with other available therapies as an emerging treatment for PPGLs that targets hostile tumor environments.
PubMed: 38377172
DOI: 10.1210/endrev/bnae005 -
The Journal of Clinical Endocrinology... Oct 2023
Topics: Humans; Pheochromocytoma; Prognosis; Neutrophils; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37011227
DOI: 10.1210/clinem/dgad192 -
Nederlands Tijdschrift Voor Geneeskunde Mar 2024Spontaneous retroperitoneal hematoma refers to bleeding of the retroperitoneal space without prior trauma or iatrogenic injury. Its diagnosis is often delayed due to a...
Spontaneous retroperitoneal hematoma refers to bleeding of the retroperitoneal space without prior trauma or iatrogenic injury. Its diagnosis is often delayed due to a nonspecific clinical presentation. This case-series presents three patients with spontaneous retroperitoneal bleeding. Patient A presented with a spontaneous bleeding around the right iliopsoas muscle due to antiplatelet medication and was managed conservatively. Patient B had a spontaneous arterial bleeding near the right kidney, subsequently determined to be associated with a pheochromocytoma. Endovascular treatment successfully stopped the bleeding. The pheochromocytoma was resected during follow-up. Patient C had a spontaneous rupture of the left iliac vein with a concomitant deep vein thrombosis. She underwent emergent laparotomy, but unfortunately did not survive. This case-series emphasize the diverse presentation, varied causes, and different treatment strategies for spontaneous retroperitoneal hematoma. Timely diagnosis is hard, but crucial to enable an individualized treatment.
Topics: Female; Humans; Pheochromocytoma; Hematoma; Gastrointestinal Hemorrhage; Platelet Aggregation Inhibitors; Rupture, Spontaneous; Adrenal Gland Neoplasms
PubMed: 38546048
DOI: No ID Found -
Scientific Reports Jul 2023Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs)....
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.
Topics: Humans; Adrenal Gland Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Cytoplasm; Paraganglioma; Peripheral Nervous System Neoplasms; Pheochromocytoma
PubMed: 37463949
DOI: 10.1038/s41598-023-38606-8 -
BMC Cardiovascular Disorders Jun 2024Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of...
BACKGROUND
Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL).
MATERIALS AND METHODS
In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT.
RESULTS
The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P < 0.001). Among 365 patients with complete echocardiography data, left ventricular mass index (86.58 ± 26.70 vs. 75.80 ± 17.26, P < 0.001) and relative wall thickness (0.43 ± 0. 08 vs. 0.41 ± 0.06, P = 0.012) were significantly higher in patients with PPGL and a history of HT. The proportions with left ventricular hypertrophy (LVH) (19.40% vs. 8.25%, P = 0.011) and LVR (53.73% vs. 39.18%, P = 0.014) were also higher when there was a history of HT. After adjusting for age, gender, body mass index, alcohol consumption, smoking status, diabetes, stroke, creatinine level, tumor location, and tumor size, a history of HT was significantly correlated with LVH (odds ratio 2.71, 95% confidence interval 1.18-6.19; P = 0.018) and LVR (odds ratio 1.83, 95% confidence interval 1.11-3.03; P = 0.018).
CONCLUSION
HT is common in patients with PPGL (70.74% in this cohort). PPGL without a history of HT is more likely to be found incidentally (59.43% in our cohort). HT is associated with LVR in PPGL patients with complete echocardiography data. These patients should be observed carefully for cardiac damage, especially those with a history of HT.
Topics: Humans; Pheochromocytoma; Male; Female; Middle Aged; Adrenal Gland Neoplasms; Adult; Ventricular Remodeling; Paraganglioma; Hypertension; Prevalence; Retrospective Studies; Ventricular Function, Left; Risk Factors; Risk Assessment; Aged; Blood Pressure
PubMed: 38926862
DOI: 10.1186/s12872-024-03936-6