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Endocrine Practice : Official Journal... Dec 2023The aim of this review was to provide a practical approach for clinicians regarding the diagnosis and management of pheochromocytomas and paragangliomas (PPGLs). (Review)
Review
OBJECTIVE
The aim of this review was to provide a practical approach for clinicians regarding the diagnosis and management of pheochromocytomas and paragangliomas (PPGLs).
METHODS
A literature search of PubMed was carried out using key words, including pheochromocytoma, paraganglioma, treatment, diagnosis, screening, and management. The discussion of diagnosis and management of PPGL is based on the evidence available from prospective studies when available and mostly from cohort studies, cross-sectional studies, and expert consensus.
RESULTS
PPGL are neuroendocrine tumors arising from the chromaffin cells of adrenal medulla and sympathetic and parasympathetic ganglia, respectively. PPGL can be localized or metastatic, and they may secrete catecholamines, causing a variety of symptoms and potentially catastrophic and lethal complications if left untreated. The rarity of these tumors along with heterogeneous clinical presentation often poses challenges for the diagnosis and management. PPGL can be associated with several familial syndromes which are important to recognize.
CONCLUSION
The last few years have witnessed an exponential growth in the knowledge around PPGL. This review aims at providing a comprehensive discussion of current concepts for clinicians regarding clinical presentation, diagnostic tools, and management strategies for PPGL.
Topics: Humans; Pheochromocytoma; Prospective Studies; Cross-Sectional Studies; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37586639
DOI: 10.1016/j.eprac.2023.07.027 -
International Braz J Urol : Official... 2023Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other... (Review)
Review
Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37115176
DOI: 10.1590/S1677-5538.IBJU.2023.0038 -
Journal of Hypertension Aug 2020: Phaeochromocytoma and paraganglioma (PPGL) are chromaffin cell tumours that require timely diagnosis because of their potentially serious cardiovascular and sometimes... (Review)
Review
Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension.
: Phaeochromocytoma and paraganglioma (PPGL) are chromaffin cell tumours that require timely diagnosis because of their potentially serious cardiovascular and sometimes life- threatening sequelae. Tremendous progress in biochemical testing, imaging, genetics and pathophysiological understanding of the tumours has far-reaching implications for physicians dealing with hypertension and more importantly affected patients. Because hypertension is a classical clinical clue for PPGL, physicians involved in hypertension care are those who are often the first to consider this diagnosis. However, there have been profound changes in how PPGLs are discovered; this is often now based on incidental findings of adrenal or other masses during imaging and increasingly during surveillance based on rapidly emerging new hereditary causes of PPGL. We therefore address the relevant genetic causes of PPGLs and outline how genetic testing can be incorporated within clinical care. In addition to conventional imaging (computed tomography, MRI), new functional imaging approaches are evaluated. The novel knowledge of genotype-phenotype relationships, linking distinct genetic causes of disease to clinical behaviour and biochemical phenotype, provides the rationale for patient-tailored strategies for diagnosis, follow-up and surveillance. Most appropriate preoperative evaluation and preparation of patients are reviewed, as is minimally invasive surgery. Finally, we discuss risk factors for developing metastatic disease and how they may facilitate personalised follow-up. Experts from the European Society of Hypertension have prepared this position document that summarizes the current knowledge in epidemiology, genetics, diagnosis, treatment and surveillance of PPGL.
Topics: Adrenal Gland Neoplasms; Biomedical Research; Consensus; Europe; Humans; Hypertension; Paraganglioma; Pheochromocytoma
PubMed: 32412940
DOI: 10.1097/HJH.0000000000002438 -
Best Practice & Research. Clinical... Mar 2020Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumours characterized by a strong genetic determinism. Over the past 20 years, evolution of PPGL... (Review)
Review
Paragangliomas and pheochromocytomas (PPGL) are rare neuroendocrine tumours characterized by a strong genetic determinism. Over the past 20 years, evolution of PPGL genetics has revealed that around 40% of PPGL are genetically determined, secondary to a germline mutation in one of more than twenty susceptibility genes reported so far. More than half of the mutations occur in one of the SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), which encode the different subunits and assembly protein of a mitochondrial enzyme, succinate dehydrogenase. These susceptibility genes predispose to early forms (VHL, RET, SDHD, EPAS1, DLST), syndromic (RET, VHL, EPAS1, NF1, FH), multiple (SDHD, TMEM127, MAX, DLST, MDH2, GOT2) or malignant (SDHB, FH, SLC25A11) PPGL. The discovery of a germline mutation in one of these genes changes the patient's follow-up and allows genetic screening of affected families and the presymptomatic follow-up of relatives carrying a mutation.
Topics: Adrenal Gland Neoplasms; DNA Mutational Analysis; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; History, 20th Century; History, 21st Century; Humans; Mutation; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 32295730
DOI: 10.1016/j.beem.2020.101416 -
The Lancet. Diabetes & Endocrinology Dec 2023Phaeochromocytomas and paragangliomas (PPGLs) release catecholamines leading to catecholamine-induced hypertensive (CIH) crises, with blood pressure greater than or... (Review)
Review
Phaeochromocytomas and paragangliomas (PPGLs) release catecholamines leading to catecholamine-induced hypertensive (CIH) crises, with blood pressure greater than or equal to 180/120 mm Hg. CIH crises can be complicated by tachyarrhythmias, hypotension, or life-threatening target organ damage while treatment remains undefined, often requiring co-management between endocrinologists and cardiologists. Furthermore, biochemical diagnosis of a PPGL as a cause of a CIH crisis can be difficult to identify or confounded by comorbid conditions, potentially resulting in misdiagnosis. Here, we combine relevant evidence, 60 years of collective clinical experience, insights derived from assessing over 2600 patients with PPGL, and supplementary outcomes from 100 patients (treated at the National Institutes of Health) with a CIH crisis to inform diagnosis and treatment of CIH crises. Recognising that disparities exist between availability, cost, and familiarity of various agents, flexible approaches are delineated allowing for customisation, given institutional availability and provider preference. A CIH crisis and its complications are readily treatable with available drugs, with effective intervention defining an avenue for mitigating consequent morbidity and mortality in patients with PPGL.
Topics: Humans; Catecholamines; Paraganglioma; Pheochromocytoma; Blood Pressure; Adrenal Gland Neoplasms
PubMed: 37944546
DOI: 10.1016/S2213-8587(23)00256-5 -
The Lancet. Diabetes & Endocrinology May 2023Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck... (Review)
Review
Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.
Topics: Humans; Adrenal Gland Neoplasms; Germ-Line Mutation; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase; Practice Guidelines as Topic
PubMed: 37011647
DOI: 10.1016/S2213-8587(23)00038-4 -
The Journal of Clinical Endocrinology... Dec 2020The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict...
PURPOSE
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.
METHODS
The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).
RESULTS
From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score.
CONCLUSION
Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.
Topics: Adrenal Gland Neoplasms; Adult; Biomarkers, Tumor; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Paraganglioma; Pennsylvania; Pheochromocytoma; Prognosis; Research Design; Retrospective Studies; Survival Analysis
PubMed: 32877928
DOI: 10.1210/clinem/dgaa608 -
Clinical & Translational Oncology :... Oct 2021Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.
Topics: Adrenal Gland Neoplasms; Aftercare; Algorithms; Biomarkers, Tumor; Catecholamines; Diagnostic Imaging; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Humans; Neoplasm Staging; Paraganglioma; Pheochromocytoma; Societies, Medical; Spain; Symptom Assessment
PubMed: 33959901
DOI: 10.1007/s12094-021-02622-9 -
European Journal of Nuclear Medicine... Sep 2019Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to...
European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma.
PURPOSE
Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results.
METHODS
Guidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals.
CONCLUSION
Since the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (I)/iodine-131 (I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.
Topics: Adrenal Gland Neoplasms; European Union; Humans; Iodine Radioisotopes; Nuclear Medicine; Pheochromocytoma; Positron-Emission Tomography; Practice Guidelines as Topic; Radiopharmaceuticals; Societies, Medical; Somatostatin
PubMed: 31254038
DOI: 10.1007/s00259-019-04398-1 -
Current Opinion in Pediatrics Aug 2021Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in... (Review)
Review
PURPOSE OF REVIEW
Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in the diagnosis and management of pediatric PPGLs.
RECENT FINDINGS
The vast majority of pediatric PPGLs have an associated germline mutation, making genetic studies imperative in the work up of these tumors. Somatostatin receptor-based imaging modalities such as 68Ga-DOTATATE and 64Cu-DOTATATE are shown to have the greatest sensitivity in pediatric PPGLs. Peptide receptor radionuclide therapies (PRRTs) such as 177Lu-DOTATATE are shown to have efficacy for treating PPGLs.
SUMMARY
Genetics play an important role in pediatric PPGLs. Advances in somatostatin receptor-based technology have led to use of 68Ga-DOTATATE and 64Cu-DOTATATE as preferred imaging modalities. While surgery remains the mainstay for management of PPGLs, PRRT is emerging as a treatment option for PPGLs.
Topics: Adrenal Gland Neoplasms; Child; Copper Radioisotopes; Humans; Paraganglioma; Pheochromocytoma
PubMed: 34039901
DOI: 10.1097/MOP.0000000000001029