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The Oncologist 2013Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Diagnostic Imaging; Humans; MicroRNAs; Mutation; Neoplasm Recurrence, Local; Paraganglioma; Pheochromocytoma; Prognosis
PubMed: 23576482
DOI: 10.1634/theoncologist.2012-0410 -
Frontiers in Endocrinology 2020Half of the patients with phaeochromocytoma have glucose intolerance which could be life-threatening as well as causing postoperative hypoglycemia. Glucose intolerance... (Review)
Review
Half of the patients with phaeochromocytoma have glucose intolerance which could be life-threatening as well as causing postoperative hypoglycemia. Glucose intolerance is due to impaired insulin secretion and/or increased insulin resistance. Impaired insulin secretion is caused by stimulating adrenergic α2 receptors of pancreatic β-cells and increased insulin resistance is caused by stimulating adrenergic α1 and β3 receptors in adipocytes, α1 and β2 receptors of pancreatic α-cells and skeletal muscle. Furthermore, different affinities to respective adrenergic receptors exist between epinephrine and norepinephrine. Clinical studies revealed patients with phaeochromocytoma had impaired insulin secretion as well as increased insulin resistance. Furthermore, excess of epinephrine could affect glucose intolerance mainly by impaired insulin secretion and excess of norepinephrine could affect glucose intolerance mainly by increased insulin resistance. Glucose intolerance on paraganglioma could be caused by increased insulin resistance mainly considering paraganglioma produces more norepinephrine than epinephrine. To conclude, the difference of actions between excess of epinephrine and norepinephrine could lead to improve understanding and management of glucose intolerance on phaeochromocytoma.
Topics: Adrenal Gland Neoplasms; Animals; Glucose Intolerance; Humans; Paraganglioma; Pheochromocytoma
PubMed: 33324347
DOI: 10.3389/fendo.2020.593780 -
Brazilian Journal of Medical and... Oct 2000Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well... (Review)
Review
Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well as in many others with suggestive symptoms or with a familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends importantly on biochemical evidence of excess catecholamine production by a tumor. Imperfect sensitivity and specificity of commonly available biochemical tests and the low incidence of the tumor among the tested population mean that considerable time and effort can be expended in confirming or ruling out pheochromocytoma in patients where the tumor is suspected. Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free metanephrines means that a normal test result reliably excludes all but the smallest of pheochromocytomas so that no other tests are necessary. Measurements of plasma free metanephrines, when systematically combined with other diagnostic procedures outlined in this review, provide a more efficient, reliable and cost-effective approach for diagnosis of pheochromocytoma than offered by previously available approaches.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Catecholamines; Chromatography, High Pressure Liquid; Cost-Benefit Analysis; Humans; Hypertension; Metanephrine; Pheochromocytoma; Sensitivity and Specificity
PubMed: 11004716
DOI: 10.1590/s0100-879x2000001000005 -
Postgraduate Medical Journal Mar 1960
Topics: Humans; Pheochromocytoma
PubMed: 13846086
DOI: 10.1136/pgmj.36.413.165 -
The Australian and New Zealand Journal... May 1988
Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Humans; Iodine Radioisotopes; Iodobenzenes; Pheochromocytoma; Radiography; Radionuclide Imaging
PubMed: 3178590
DOI: 10.1111/j.1445-2197.1988.tb01080.x -
Langenbeck's Archives of Surgery Feb 2012Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from... (Comparative Study)
Comparative Study Review
INTRODUCTION
Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from paraganglia along the sympathetic trunk. According to the WHO classification, malignancy of PCCs and PGLs is defined by the presence of metastases at non-chromaffin sites distant from that of the primary tumor and not by local invasion. The overall prognosis of metastasized PCCs/PGLs is poor. Surgery offers currently the only change of cure. Preferably, the discrimination between malignant and benign PCCs/PGLs should be made preoperatively.
METHODS
This review summarizes our current knowledge on how benign and malignant tumors can be distinguished.
CONCLUSION
Due to the rarity of malignant PCCs/PGLs and the obvious difficulties in distinguishing benign and malignant PCCs/PGLs, any patient with a PCC/PGL should be treated in a specialized center where a multidisciplinary setting with specialized teams consisting of radiologists, endocrinologist, oncologists, pathologists and surgeons is available. This would also facilitate future studies to address the existing diagnostic and/or therapeutic obstacles.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Animals; Biopsy, Needle; Chemotherapy, Adjuvant; Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Immunohistochemistry; Male; Neoplasm Staging; Paraganglioma; Pheochromocytoma; Prognosis; Radiotherapy, Adjuvant; Survival Analysis
PubMed: 22124609
DOI: 10.1007/s00423-011-0880-x -
Advances in Clinical and Experimental... 2012Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and... (Review)
Review
Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bβ, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view.
Topics: Adrenal Gland Neoplasms; Genes, Neoplasm; Genetic Predisposition to Disease; Humans; Mutation; Pheochromocytoma; Syndrome
PubMed: 23457139
DOI: No ID Found -
Journal of Endocrinological... Jan 2022Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in...
BACKGROUND
Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5-26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines.
AIM
The aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs.
METHODS
Clinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27.
RESULTS
Nine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30-55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p < 0.001), abdominal PGLs (OSpt p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008).
CONCLUSION
Our data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.
Topics: Adrenal Gland Neoplasms; Adult; Female; Humans; Italy; Male; Middle Aged; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Prognosis; Retrospective Studies; Survival Analysis; Treatment Outcome; Watchful Waiting
PubMed: 34227051
DOI: 10.1007/s40618-021-01629-x -
Yonsei Medical Journal Jan 2011We report herein 119 patients with pheochromocytoma at our institute over the last 23 years.
PURPOSE
We report herein 119 patients with pheochromocytoma at our institute over the last 23 years.
MATERIALS AND METHODS
Between 1986 and 2009, 119 patients were diagnosed with pheochromocytoma at our institute. We reviewed the medical records of these patients.
RESULTS
Of 119 patients, 45 were male and 74 were female, and mean age was 43.83 ± 13.49 years. Forty-three patients (36.1%) were diagnosed incidentally, and 8 patients (6.7%) were found to have familial pheochromocytoma. The mean dimension of the tumors was 5.89 ± 3.18 cm. 4 patients had bilateral tumors; three of these patients were found to have familial pheochromocytoma and 1 patient was diagnosed with malignant pheochromocytoma. A total of eight patients (6.7%) were found to have malignant pheochromocytoma. In 1 patient, metastasis to a lymph node was found at the time of diagnosis. Metastases were found at a mean of 49 ± 25.83 (6-75) months after surgery in the other seven patients. 6 patients died of malignant pheochromocytoma at a mean of 31 ± 28.71 months (1-81) after diagnosis, and the other 2 patients survived for 15 and 24 months, respectively.
CONCLUSION
Approximately 35% of patients with pheochromocytoma are diagnosed incidentally, and the number of detected cases is increasing. Although familial pheochromocytoma was found only in 6.7% of the patients, genetic testing should be considered in all patients, especially in patients with a family history, young age, or multifocal, bilateral, extra-adrenal, or malignant tumors. Given that malignant pheochromocytomas are frequently diagnosed during the follow-up period, long-term follow-up is necessary to confirm the absence of recurrence or metastasis.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Pheochromocytoma; Young Adult
PubMed: 21155034
DOI: 10.3349/ymj.2011.52.1.45 -
The Netherlands Journal of Medicine Sep 2006Phaeochromocytoma is a rare catecholamine-secreting neuroendocrine tumour with a high cardiovascular morbidity and mortality if left untreated. Surgical resection is the... (Review)
Review
Phaeochromocytoma is a rare catecholamine-secreting neuroendocrine tumour with a high cardiovascular morbidity and mortality if left untreated. Surgical resection is the only curative therapy. During surgery there is a high risk of massive release of catecholamines, which can result in potentially fatal hypertensive crises and cardiac arrhythmias. Administration of vasoactive drugs such as (non)selective alpha- and beta-antagonists and calcium channel blocking agents have reduced the operation risk. Guidelines for the preoperative medical management of the patient with a phaeochromocytoma are mainly based on retrospective studies and case reports. We reviewed the relevant literature on this subject. In addition, we compared the several preoperative treatment protocols of the eight university medical centres in the Netherlands.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Calcium Channel Blockers; Cardiovascular Diseases; Humans; Pheochromocytoma; Postoperative Complications; Preoperative Care; Prognosis
PubMed: 16990692
DOI: No ID Found