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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 -
Frontiers in Endocrinology 2021Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This... (Review)
Review
Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both "cold", particularly octreotide and lanreotide, and "hot" analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with Ga-DOTATATE and Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Pheochromocytoma; Precision Medicine; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 33854479
DOI: 10.3389/fendo.2021.625312 -
Langenbeck's Archives of Surgery Mar 2022Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a... (Review)
Review
INTRODUCTION
Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a single centre's records and presents a systematic literature review of composite phaeochromocytomas.
METHODS
In addition to describing 2 case reports, a systematic search of the Medline database from inception up to April 2020 was done for human case reports on composite phaeochromocytomas. Relevant titles and/or abstracts were screened, and full texts were reviewed to identify appropriate studies. Data was extracted and a descriptive analysis of presentation, clinical features, management strategies and outcomes was performed. The quality of included studies was assessed using a critical appraisal checklist.
RESULTS
There were 62 studies included, with a total of 94 patients. Of 91 patients where data was available, the median (range) age of patients was 48 (4-86) years. Of 90 patients where information was provided, 57% were female. In at least 28% of patients, a genetic cause was identified. Common presenting features include abdominal pain, palpable mass, cardiovascular and gastrointestinal symptoms. The most common tumour component with phaeochromocytoma is ganglioneuroma; other components include ganglioneuroblastoma, neuroblastoma and malignant peripheral nerve sheath tumours. In patients with follow-up data (n=48), 85% of patients were alive and well at a median (range) follow-up time of 18 (0.5-168) months.
CONCLUSION
Composite phaeochromocytoma is a rare tumour, with a significant genetic predisposition. This review summarises available epidemiological data, which will be useful for clinicians managing this rare condition.
Topics: Adrenal Gland Neoplasms; Aged; Aged, 80 and over; Brain Neoplasms; Female; Humans; Middle Aged; Pheochromocytoma
PubMed: 33651160
DOI: 10.1007/s00423-021-02129-5 -
Cell and Tissue Research May 2018Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the... (Review)
Review
Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.
Topics: Adrenal Gland Neoplasms; Humans; Molecular Imaging; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Theranostic Nanomedicine
PubMed: 29450723
DOI: 10.1007/s00441-018-2791-4 -
Hormone and Metabolic Research =... Jul 2019Since Felix Fränkel's account of pheochromocytoma in 1886, great discoveries and vast advancements in the diagnosis, genetics, anatomical and functional imaging... (Review)
Review
Since Felix Fränkel's account of pheochromocytoma in 1886, great discoveries and vast advancements in the diagnosis, genetics, anatomical and functional imaging techniques, and surgical management of pheochromcytoma and paraganglioma (P-PGL) have been made. The improved insight in the pathophysiology of P-PGL and more accurate detection methods enable physicians to tailor the treatment plan to an individual based on the genetic profile and tumor behavior. This review will cover briefly the clinical features, diagnosis, genetic mutations, and imaging modalities that are used to guide current surgical management of these rare and interesting endocrinopathies.
Topics: Adrenal Gland Neoplasms; Humans; Mutation; Pheochromocytoma; Precision Medicine
PubMed: 31307109
DOI: 10.1055/a-0926-3618 -
Best Practice & Research. Clinical... Aug 2012Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy studies indicate that relatively large numbers of these tumours remain undiagnosed during... (Review)
Review
Phaeochromocytomas and paragangliomas are neural crest-derived tumours. Autopsy studies indicate that relatively large numbers of these tumours remain undiagnosed during life. This may reflect non-specific signs and symptoms and low medical alertness in evaluating the clinical picture or it may reflect a silent clinical presentation - the subclinical phaeochromocytoma. The associated clinical picture depends on the capacity of the tumours to release catecholamines and sometimes biologically active peptides. Hypertension is the hallmark of catecholamine release, but the amount, type and pattern of catecholamine secretion is extremely variable. Some tumours have low or intermittent secretory activity, some produce mainly or solely dopamine, while others very rarely do not synthesize or release any catecholamines (non-secretory or non-functional tumours). Such tumours may present with mild or even absent signs and symptoms of catecholamine excess. Low secretory activity may reflect small tumour size or differences in secretory phenotypes associated with the biochemical and genetic background of the tumours. Tumours due to succinate dehydrogenase subunit B mutations are often subclinical, poorly differentiated, contain low amounts of catecholamines, and are usually malignant at diagnosis. Adrenoceptor desensitization can result in a subclinical presentation, even when catecholamine levels are high. Subclinical phaeochromocytomas are often discovered as incidentalomas during radiological procedures or during routine screening for phaeochromocytoma in carriers of mutations in one of the ten currently identified tumour susceptibility genes. Undiagnosed phaeochromocytomas, whether or not subclinical and even if biologically benign, may cause extremely deleterious consequences or even death, following abrupt release of catecholamines.
Topics: Adrenal Gland Neoplasms; Catecholamines; Humans; Pheochromocytoma
PubMed: 22863392
DOI: 10.1016/j.beem.2011.10.008 -
Reviews in Cardiovascular Medicine Dec 2021Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism,... (Review)
Review
Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism, phaeochromocytoma-paraganglioma (PPGL), and primary hyperaldosteronism are rare. PPGL is a rare catecholamine-secreting neuroendocrine tumour arising from the adrenal gland in 80-85% or extra-adrenal chromaffin cells of the autonomic neural ganglia in the remainder. The annual incidence of PPGL is 3-8 cases per million per year in the general population. Catecholamine-induced cardiomyopathy (CICMP) has got a prevalence of 8-11% among patients with PPGL. Hypertension, either sustained or episodic, is present in the vast majority (95%) of PPGL patients. However, among patients with CICMP, hypertension is present only in 65% of cases and the classical triad of paroxysmal headache, sweating, and palpitation is present only in 4%. Based on the cardiac remodelling in response to endogenous catecholamine excess, PPGL patients might present with one of the three CICMPs, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or Takotsubo cardiomyopathy (TCM). Regardless of the subtypes, all CICMPs have many features in common - a dramatic clinical presentation, reversible cardiomyopathy, similar repolarisation electrocardiography changes, mild-moderate cardiac biomarker elevation, and normal coronary arteries on coronary angiography. CICMP should be suspected in patients with non-ischaemic, non-valvular forms of cardiomyopathy, even in those without definite features of catecholamine excess. PPGL associated TCM should be suspected in all acute coronary syndrome (ACS) patients exhibiting pronounced blood pressure variability with no culprit lesions on coronary angiography. This article will provide a review of the various CICMPs, their pathophysiology, clinical features, and the management options.
Topics: Adrenal Gland Neoplasms; Cardiomyopathies; Catecholamines; Endocrinologists; Humans; Pheochromocytoma
PubMed: 34957765
DOI: 10.31083/j.rcm2204130 -
Oncotarget Apr 2017Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year.... (Review)
Review
Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 25-30% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics.
Topics: Adrenal Gland Neoplasms; Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genetic Variation; Humans; Paraganglioma; Pheochromocytoma; Signal Transduction
PubMed: 28187001
DOI: 10.18632/oncotarget.15201 -
Hormone and Metabolic Research =... May 2012After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging... (Review)
Review
After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using 123I-metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no 'gold-standard' imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.
Topics: Adrenal Gland Neoplasms; Animals; Diagnostic Imaging; Humans; Paraganglioma; Pheochromocytoma; Radionuclide Imaging
PubMed: 22399235
DOI: 10.1055/s-0031-1299712 -
Veterinary Pathology May 2019Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In...
Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Female; Male; Pheochromocytoma; Prognosis
PubMed: 30595108
DOI: 10.1177/0300985818819174