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British Medical Journal Mar 1963
Topics: Guanethidine; Humans; Pheochromocytoma
PubMed: 13982863
DOI: 10.1136/bmj.1.5332.729 -
Clinical Endocrinology Nov 2017The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The outcomes of patients with metastatic phaeochromocytoma (PHEO) and paraganglioma (PGL) are unclear. We performed a systematic review and meta-analysis of baseline characteristics and mortality rates of patients with metastatic PHEO and PGL (PPGL).
DESIGN
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, Web of Science, and references of key articles were searched from inception to 2016.
PATIENTS
Studies comprised ≥20 patients with metastatic PPGL and reported baseline characteristics and follow-up data.
MEASUREMENTS
Reviewers extracted standardized data and assessed risk of bias using a modified Newcastle-Ottawa tool. Random-effects meta-analysis was used to pool event rates across studies.
RESULTS
Twenty retrospective noncomparative studies reported on 1338 patients with metastatic PHEO (685/1296, 52.9%) and PGL (611/1296, 47.1%), diagnosed at a mean age of 43.9 ± 5.2 years. Mean follow-up was 6.3 ± 3.2 years. Of 532 patients with reported data, 40.4% had synchronous metastases. Five-year (7 studies, n = 738) and 10-year (2 studies, n = 55) mortality rates for patients with metastatic PPGL were 37% (95% CI, 24%-51%) and 29% (95% CI, 17%-42%), respectively. Higher mortality was associated with male sex (RR 1.50; 95% CI, 1.11-2.02) and synchronous metastases (RR 2.43; 95% CI, 1.01-5.85).
CONCLUSIONS
Available low-quality evidence from heterogeneous studies suggests low mortality rates of patients with metastatic PPGL. Male sex and synchronous metastases correlated with increased mortality. The outcomes of patients with metastatic PPGL have been inadequately assessed, indicating the need for carefully planned prospective studies.
Topics: Adrenal Gland Neoplasms; Adult; Female; Humans; Male; Middle Aged; Mortality; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Treatment Outcome
PubMed: 28746746
DOI: 10.1111/cen.13434 -
Journal of Internal Medicine Jul 2009A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an... (Review)
Review
A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel 'paraganglioma-phaeochromocytoma syndrome' caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest-derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent-of-origin effect for SDHD mutations. Life-time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Cell Transformation, Neoplastic; Child; Child, Preschool; Genetic Predisposition to Disease; Germ-Line Mutation; Head and Neck Neoplasms; Humans; Middle Aged; Neoplastic Syndromes, Hereditary; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 19522823
DOI: 10.1111/j.1365-2796.2009.02111.x -
Journal of Internal Medicine Jan 2005Approximately 50% of patients with multiple endocrine neoplasia (MEN) 2A or 2B develop pheochromocytoma. These tumours are almost exclusively benign and localized in the... (Review)
Review
Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour.
Approximately 50% of patients with multiple endocrine neoplasia (MEN) 2A or 2B develop pheochromocytoma. These tumours are almost exclusively benign and localized in the adrenal glands. About one-third are bilateral at initial diagnosis. Amongst patients with pheochromocytoma, those with MEN 2A have subtler symptoms compared to those with sporadic disease. Since pheochromocytomas in patients with MEN 2 often secrete catecholamines episodically (but metabolize them continuously to metanephrines), the first choice for biochemical diagnosis is the measurement of free metanephrines in plasma, with urinary fractionated metanephrines being the second choice. In patients with pheochromocytomas that produce exclusively normetanephrine, MEN 2 can be excluded. In patients with biochemically proven MEN 2-related pheochromocytoma, anatomical imaging of the adrenals (with either computerized tomography or magnetic resonance) should be obtained next. Functional imaging with specific ligands (e.g. scintigraphy with [(123)I]-metaiodobenzylguanidine or, if available, positron emission tomography with [(18)F]-fluorodopamine, [(18)F]-dihydroxyphenylalanine, [(11)C]-adrenaline or [(11)C]-hydroxyephedrine) may then be particularly useful in patients with distorted anatomy from previous surgery, in cases of equivocal biochemical data despite high clinical suspicion for a tumour, to rule out multifocal disease, or where there is suspicion of metastatic disease (e.g. tumours larger than 5 cm). Laparoscopic surgery is the treatment of choice and subtotal (cortical-sparing) adrenalectomy is the procedure of choice in bilateral pheochromocytomas.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Adult; Female; Humans; Magnetic Resonance Imaging; Male; Metanephrine; Multiple Endocrine Neoplasia; Pheochromocytoma; Tomography, X-Ray Computed
PubMed: 15606377
DOI: 10.1111/j.1365-2796.2004.01425.x -
Clinical Endocrinology Oct 2022Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with malignant potential and a hereditary basis in almost 40% of patients. Germline genetic... (Review)
Review
OBJECTIVES
Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with malignant potential and a hereditary basis in almost 40% of patients. Germline genetic testing has transformed the management of PPGL enabling stratification of surveillance approaches, earlier diagnosis and predictive testing of at-risk family members. Recent studies have identified somatic mutations in a further subset of patients, indicating that molecular drivers at either a germline or tumour level can be identified in up to 80% of PPGL cases. The aim of this study was to investigate the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom.
DESIGN AND PATIENTS
Prospectively collected matched germline and tumour samples (development cohort) and retrospectively collected tumour samples (validation cohort) of patients with PPGL were investigated.
MEASUREMENTS
Clinical characteristics of patients were assessed and tumour and germline DNA was analysed using a next-generation sequencing strategy. A screen for variants within 'mutation hotspots' in 68 human cancer genes was performed.
RESULTS
Of 141 included patients, 45 (32%) had a germline mutation. In 37 (26%) patients one or more driver somatic variants were identified including 26 likely pathogenic or pathogenic variants and 19 variants of uncertain significance. Pathogenic somatic variants, observed in 25 (18%) patients, were most commonly identified in the VHL, NF1, HRAS and RET genes. Pathogenic somatic variants were almost exclusively identified in patients without a germline mutation (all but one), suggesting that somatic sequencing is likely to be most informative for those patients with negative germline genetic test results.
CONCLUSIONS
Somatic sequencing may further stratify surveillance approaches for patients without a germline genetic driver and may also inform targeted therapeutic strategies for patients with metastatic disease.
Topics: Adrenal Gland Neoplasms; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Paraganglioma; Pheochromocytoma; Retrospective Studies
PubMed: 34870338
DOI: 10.1111/cen.14639 -
South African Family Practice :... Jul 2021Most cases of hypertension are because of essential hypertension, however 5% - 15% of cases can be a result of a secondary cause. In this article, we focus on the...
Most cases of hypertension are because of essential hypertension, however 5% - 15% of cases can be a result of a secondary cause. In this article, we focus on the endocrine causes of secondary hypertension with a particular focus on pheochromocytomas (PCCs) and paragangliomas (PGLs). Around 15 endocrine disorders can initially present with hypertension. Amongst those PCCs and PGLs are rare but potentially life-threatening causes. An early diagnosis and timely referral can be life-saving. Herein, we present an approach for screening and diagnosis of these patients and focus on the importance of genetic testing.
Topics: Adrenal Gland Neoplasms; Genetic Testing; Humans; Hypertension; Paraganglioma; Pheochromocytoma
PubMed: 34342483
DOI: 10.4102/safp.v63i1.5277 -
Postgraduate Medical Journal Apr 1996Adrenal incidentalomas present a significant differential diagnostic challenge. All patients with an incidentally discovered adrenal lesion should be carefully... (Review)
Review
Adrenal incidentalomas present a significant differential diagnostic challenge. All patients with an incidentally discovered adrenal lesion should be carefully considered and re-evaluated to exclude extra-adrenal malignancy. Tumours with hypersecretory syndromes require excision, whilst those tumours more than 6 cm in size, particularly if they exhibit other features of malignancy on computed tomography (CT), magnetic resonance imaging (MRI) or scintigraphy, should also be excised. In all cases screening for phaeochromocytomas should be performed, and in the context of hypertension and spontaneous hypokalaemia, a primary aldosterone-secreting tumour requires exclusion. However, the natural history and treatment regimens for those individuals demonstrating 'subclinical Cushing's syndrome' is far from clear. Size, as determined by CT or MR scanning, does not in itself reliably distinguish benign from malignant disease. Scintigraphy may be a useful adjunct, with discordant patterns suggesting malignant disease. Fine needle aspiration should not routinely be used but may be useful in cases of doubt about other extra adrenal malignancy.
Topics: Adenoma; Adrenal Gland Neoplasms; Cushing Syndrome; Humans; Pheochromocytoma; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 8733526
DOI: 10.1136/pgmj.72.846.207 -
Annals of Medicine Dec 2023Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series....
BACKGROUND
Pheochromocytomas and paragangliomas (PPGLs) are a group of rare neuroendocrine tumors. Dysglycemia has been observed in patients with PPGLs in some small case series. However, there is limited information available on the factors associated with development and resolution of dysglycemia in these patients.
PATIENTS AND METHODS
The clinical data of consecutive patients admitted to our hospital with PPGLs between January 2018 and June 2020 were retrospectively analyzed. Clinical characteristics were compared between patients with and without dysglycemia. Logistic regression analysis was used to identify risk factors and receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the variables.
RESULTS
Among 163 patients, 58.9% had preoperative dysglycemia. Patients with dysglycemia were significantly older at diagnosis ( = 0.01) and were significantly more likely to have hypertension ( = 0.007). White blood cell counts ( = 0.016), 24-hour urinary epinephrine (24hU-E) levels ( < 0.001) and 24-hour urinary norepinethrine levels ( = 0.008) were significantly higher in patients with dysglycemia. Regression analysis showed that age (odds ratio [OR] 1.028, 95% confidence interval [CI] 1.001-1.055; = 0.041), hypertension (OR 2.164, 95% CI 1.014-4.619; = 0.046) and the 24hU-E concentration (OR 1.010, 95% CI, 1.001-1.019; = 0.025) were positively associated with preoperative dysglycemia. Taking age, hypertension, and 24hU-E into account in the same model, the area under the ROC curve for prediction of preoperative dysglycemia was 0.703. The proportion of patients with dysglycemia decreased significantly after surgery ( < 0.001) and patients with preoperative dyssglycemia that resolved after surgery tended to have a larger preoperative tumor diameter ( = 0.018).
CONCLUSION
Age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia. Removal of PPGLs can improve dysglycemia in most patients, and postoperative remission of dysglycemia is associated with the preoperative tumor diameter. These results are important for risk assessment and for selecting optimal therapies in patients with dysglycemia in PPGLs.KEY MESSAGESThere have been insufficient data to identify factors associated with development and resolution of dysglycemia in patients with PPGLs.Our results show that approximately half of the patients with PPGLs develop dysglycemia; age, hypertension, and the 24hU-E concentration are risk factors for preoperative dysglycemia.Removal of the PPGLs improves dysglycemia in a majority of patients, and a large preoperative tumor diameter is associated with remission of dysglycemia after surgery.
Topics: Humans; Pheochromocytoma; Catecholamines; Retrospective Studies; Paraganglioma; Adrenal Gland Neoplasms; Hypertension
PubMed: 37129505
DOI: 10.1080/07853890.2023.2203945 -
British Heart Journal Mar 1974
Topics: Adult; Blood Pressure; Female; Heart Neoplasms; Humans; Mitral Valve Insufficiency; Pheochromocytoma; Radiography
PubMed: 4824541
DOI: 10.1136/hrt.36.3.318 -
Medicine Jan 2021Phaeochromocytomas are catecholamine-producing neuroendocrine tumors that may manifest in many ways, specifically as sustained or paroxysmal hypertension. Data,...
Phaeochromocytomas are catecholamine-producing neuroendocrine tumors that may manifest in many ways, specifically as sustained or paroxysmal hypertension. Data, including data from mental status screening, were prospectively collected from suspected patients. The Hospital Anxiety and Depression Scale was used as a screening tool to identify abnormal mental status. Results showed phaeochromocytoma patients were more likely to experience anxiety and depression. For future phaeochromocytoma treatment, early screening for anxiety and depression should be recommended.
Topics: Adrenal Gland Neoplasms; Adult; Aged; Anxiety; Case-Control Studies; China; Depression; Humans; Logistic Models; Middle Aged; Pheochromocytoma; Psychometrics; Translating
PubMed: 33546066
DOI: 10.1097/MD.0000000000024335