Pheochromocytoma and Paraganglioma
Paragangliomas are rare tumors which form in neural crest tissue, a type of nerve tissue found in the adrenal glands and near certain blood vessels and nerves throughout the body. Paragangliomas that develop in the adrenal glands are called pheochromocytomas. Those that develop outside the adrenal glands ('extra-adrenal') are called paragangliomas. Most of these tumors are considered to be benign and about a quarter of cases are known to be related to inherited genetic conditions.
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MeSH term: Paraganglioma
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Pheochromocytoma, paragangliomas, and pituitary adenoma: An unusual association in a patient with an SDHD mutation. Case report.
Medicine (Baltimore). 2019; 98(30):e16594 [PubMed] Related Publications
PATIENT CONCERNS: We here report a 31-year-old patient with a known SDHD mutation whose disease has been revealed by a left PHEO during childhood and who presented at age 29 years a large paraganglioma of the right jugular foramen, a concomitant PHEO of the left adrenal and 2 retroperitoneal paragangliomas. A pituitary incidentaloma was found during investigations on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).
DIAGNOSIS: A pituitary magnetic resonance imaging (MRI) confirmed the presence of a 14 mm pituitary macroadenoma. The pituitary function was normal except for hypogonadotropic hypogonadism. On examination of the fundus, a diagnosis of Pseudo Foster-Kennedy syndrome was made due to a venous compression of the right jugular vein caused by the paraganglioma (PGL). The pituitary adenoma was not compressive to the optic chiasm.
INTERVENTIONS: A treatment with acetazolamide was started in order to improve intracranial hypertension. The patient couldn't benefit of a surgical approach for the paraganglioma of the right jugular foramen; the patient has been treated with stereotactic radiosurgery (Gamma Knife).
OUTCOMES: The most recent MRI revealed that the right jugular foramen PGL is stable and the latest visual assessment demonstrated stability despite a recent reduction in acetazolamide dosage. A surveillance by MRI of the pituitary adenoma has been planned.
LESSONS: The association of a pituitary adenoma to paragangliomas within a same patient is very uncommon and raises the question of related physiopathological mechanisms.
A large pheochromocytoma requiring aortic and inferior vena caval reconstruction: A case report.
Medicine (Baltimore). 2019; 98(29):e16494 [PubMed] Related Publications
PATIENT CONCERNS: We here report a case of a large pheochromocytoma in a 56-year-old woman who complained of only hand trembling and had no hypertension or other symptoms. The operation was difficult because of a tight adhesion to the circumference of great vessels. A replacement of the aortocaval vessels with grafts was necessary to remove the tumor completely.
DIAGNOSES: Ultrasonography, computed tomography (CT), and catecholamine assay revealed suspecting the retroperitoneal PCC.
INTERVENTIONS: Tumor excision and reconstruction of the abdominal aorta and inferior vena cava by externally supported polytetrafluoroethylene (ePTFE) vessels were successfully performed.
OUTCOMES: A follow-up CT angiography showed no recurrence and graft vessels presented good patency after 7years. Catecholamine in urine and serum assay was normal.
LESSONS: The complete resection of the tumor and infiltrated great vessels were necessary for the long-term survival of patients with a large PCC. The ePTFE graft is a good substitute for vessel reconstruction.
Asymptomatic left posterior mediastinal functional paraganglioma: A case report.
Medicine (Baltimore). 2019; 98(28):e16383 [PubMed] Free Access to Full Article Related Publications
PATIENT CONCERNS: We report a 47-year-old man with a functional paraganglioma in the left posterior mediastinum and highlight the key elements of management of mediastinal paragangliomas.
DIAGNOSES: A left posterior mediastinal mass was found by computed tomography (CT) scan and Chest-enhanced CT. Preoperative ultrasound-guided biopsy suggested the possibility of a paraganglioma. A diagnosis of paraganglioma was established by immunohistochemistry.
INTERVENTIONS: The patient underwent single-stage resection of the lesion via left thoracotomy after preoperative oral α-adrenoceptor (phenoxybenzamine) therapy and intravenous fluid resuscitation for two weeks.
OUTCOMES: The postoperative period was uneventful. The patient exhibited no abnormal blood pressure or recurrence during the 12-month follow-up period.
LESSONS SUBSECTIONS AS PER STYLE: Pathological examination alone cannot determine whether it was a benign or malignant paraganglioma, which can be determined by pathological examination combined with distant metastasis. Long-term follow-up is required to assess the treatment effect.
Electrical Remodeling of Ventricular Repolarization Abnormality after Treatment in Pheochromocytoma: U Wave Finding in a Retrospective Analysis.
Biomed Res Int. 2019; 2019:2605323 [PubMed] Free Access to Full Article Related Publications
Objectives: Analysis of abnormal ventricular repolarization focused on the presence and amount of U wave in patients affected by pheochromocytoma and its modification after surgery.
Materials and Methods: We reviewed pathology records of 722 patients admitted for adrenal nodule or suspected chromaffin-cell tumor and identified 39 patients affected by pheochromocytoma. Metanephrine, normetanephrine, and 3-methoxytyramine have been assessed by determining concentrations in 24-hour urine collection. Standard 12-lead electrocardiogram records have been reviewed with analysis of heart rate, P wave, PR interval, QRS duration, QTc, and U wave. Then we selected and compared 22 patients of 39 affected by pheochromocytoma, with both clinical and electrocardiographic data before and after surgery.
Results: In our cohort of 39 patients affected by pheochromocytoma, we found U wave in ECG, before treatment, in 82.8 percent of patients, while only 37.0 percent after treatment (p<0.001) and we observed a statistically significant correlation between this wave and the urinary metanephrine. After surgery, in the selected 22 patients, we observed a clear significant reduction in systemic blood pressure, fasting glucose, metanephrine, normetanephrine, and 3-methoxytyramine. We found a significant reduction of U wave presence and leads involved in these patients after surgery (90.9% versus 9%). We observed a linear correlation between the amount of U waves in 12-lead electrocardiogram and metanephrine (r
Conclusions: In our retrospective analysis, patients affected by pheochromocytoma presented U wave in electrocardiogram. The presence and amount of U wave were associated with the metanephrine levels and the tumor size with significant reduction after surgical removal.
Role of Preoperative Embolization in Surgical Treatment of the Carotid Body Paragangliomas.
J Craniofac Surg. 2019 May/Jun; 30(3):e267-e270 [PubMed] Related Publications
Detection of Plasma Catecholamines in Human Pheochromocytoma and Primary Hypertension Based on Liquid Chromatography Tandem Mass Spectrometry.
Ann Clin Lab Sci. 2019; 49(2):204-211 [PubMed] Related Publications
METHODS: Plasma samples were extracted by acetonitrile and derivatized with DNS-Cl, followed by reverse phase separation and triple quadruple detection. Quantification of the CAs and their derivatives in 10 PPGL, 10 PH, and 100 healthy subjects was performed by UPLC-MS/MS analysis.
RESULTS: All the values of detected CAs/derivatives were in the linearity ranges of the fitted curves. The expression levels of the seven CAs in the PPGL and PH patients were significantly higher than the healthy controls, suggesting increased CA production in the former. There were significant differences in plasma NE, NMN, and VMA levels between the PPGL and PH patients, but there was no significant difference in plasma E, MN, DA, and HVA. A discriminant analysis showed that 90% of the final cases were classified correctly based on the detected CAs/derivatives.
CONCLUSIONS: Our results show that the combined detection of the seven CAs/derivatives could be used for the clinical diagnosis of PPGL and PH.
Synchronous Paraganglioma Masquerading as 68Ga-PSMA PET/CT-Avid Metastasis in Carcinoma Prostate-How Specific Is 68Ga-PSMA PET/CT?
Clin Nucl Med. 2019; 44(6):e420-e422 [PubMed] Related Publications
In Vivo PSMA Expression in Head and Neck Paragangliomas on 68Ga PSMA 11 PET/CT.
Clin Nucl Med. 2019; 44(6):e398-e400 [PubMed] Related Publications
Giant Cell Tumor of the Carotid Body: A Rare Tumor in a Novel Location.
Ear Nose Throat J. 2019; 98(3):165-168 [PubMed] Related Publications
SYMPATHETIC PARAGANGLIOMA: A SINGLE-CENTER EXPERIENCE FROM WESTERN INDIA.
Endocr Pract. 2019; 25(3):211-219 [PubMed] Related Publications
METHODS: This retrospective study included 75 patients with sPGL and 150 patients with PCC. Diagnosis of PCC/PGL was based on surgical histopathology, and if histopathology was not available, on biochemistry and/or radiology.
RESULTS: sPGL was more frequently detected incidentally ( P = .03), normetanephrine-secreting ( P<.01), and metastatic compared with PCC ( P≤.01). sPGL was most commonly located in the organ of Zuckerkandl (OOZ) (49%) and infradiaphragmatic area above the OOZ (27%). Patients with mediastinal sPGL were significantly older than those with sPGL in the OOZ ( P = .03). Primary tumors of metastatic sPGL were significantly larger than those without metastasis (7.8 ± 4 cm vs. 5.6 ± 3.2 cm; P = .004). Percentage arterial enhancement (PAE) >100% was seen in 98% of sPGLs.
CONCLUSION: Incidental presentation, normetanephrine-secreting phenotype, and metastatic disease were more frequent in patients with sPGL than those with PCC. sPGL arose most commonly in the OOZ. Tumor size is an independent predictor of malignancy among sPGL patients. PAE >100% is almost a universal finding in sPGL, and its absence is a sensitive parameter to differentiate sPGL from other abdominal masses.
ABBREVIATIONS: AP = arterial phase; CECT = contrast-enhanced computed tomography; CT = computed tomography; DP = delayed phase; EVP = early venous phase; FDG = fluorodeoxyglucose; fPFMN = fractionated plasma free metanephrine; HU = Hounsfield units; MIBG = metaiodobenzylguanidine; MRI = magnetic resonance imaging; OOZ = organ of Zuckerkandl; PAE = percentage arterial enhancement; PCC = pheochromocytoma; PET = positron emission tomography; PFNMN = plasma free normetanephrine; PGL = paraganglioma; PRRT = peptide receptor radionuclide therapy; PVE = percentage venous enhancement; sPGL = sympathetic paraganglioma; UP = unenhanced phase; VMA = vanillyl mandelic acid.
Age-specific pediatric reference intervals for plasma free normetanephrine, metanephrine, 3-methoxytyramine and 3-O-methyldopa: Particular importance for early infancy.
Clin Chim Acta. 2019; 494:100-105 [PubMed] Related Publications
METHODS: Plasma concentrations of 3-methoxytyramine, normetanephrine, metanephrine, and 3-O-methyldopa were analyzed by liquid chromatography tandem mass spectrometry in 533 children aged 2 days to 18 years.
RESULTS: Concentrations of plasma free normetanephrine, 3-methoxytyramine and 3-O-methyldopa were higher in neonates up until six months of age, but thereafter declined steeply to levels after one year that were <38% those of neonatal concentrations and to further lower concentrations in teenagers that were <23% those in neonates. In contrast, concentrations of plasma free metanephrine showed a reciprocal pattern with 50% lower concentrations in infants below one year compared to later in childhood.
CONCLUSION: The dynamic reciprocal changes in plasma concentrations of normetanephrine, 3-methoxytyramine and 3-O-methyldopa compared to metanephrine during early childhood suggest underlying developmental changes in extra-adrenal and adrenal chromaffin tissue that must be considered for pediatric reference intervals, particularly in infants. With such reference intervals at hand, biochemical testing for catecholamine producing tumors in young children is substantially improved.
A Systematic Review and Meta-Analysis of the Presentation and Surgical Management of Patients With Carotid Body Tumours.
Eur J Vasc Endovasc Surg. 2019; 57(4):477-486 [PubMed] Related Publications
METHODS: This is a systematic review and meta-analysis of 104 observational studies.
RESULTS: Overall, 4418 patients with 4743 CBTs were identified. The mean age was 47 years, with the majority being female (65%). The commonest presentation was a neck mass (75%), of which 85% were painless. Dysphagia, cranial nerve injury (CNI), and headache were present in 3%, while virtually no one presented with a transient ischaemic attack (0.26%) or stroke (0.09%). The majority (97%) underwent excision, but only 21% underwent pre-operative embolisation. Overall, 27% were Shamblin I CBTs; 44% were Shamblin II; and 29% were Shamblin III. The mean 30 day mortality was 2.29% (95% CI 1.79-2.93). The mean 30 day stroke rate was 3.53% (95% CI 2.91-4.29), while the mean 30 day CNI rate was 25.4% (95% CI 24.5-31.22). The prevalence of persisting CNI at 30 days was 11.15% (95% CI 8.42-14.64). Twelve series (544 patients) correlated 30 day stroke with Shamblin status. Shamblin I CBTs were associated with a 1.89% stroke rate (95% CI 0.92-3.82), increasing to 2.71% (95% CI 1.43-5.07) for Shamblin II CBTs and 3.99% (95% CI 2.34-6.74) for Shamblin III tumours. Twenty-six series (1075 patients) correlated CNI rates with Shamblin status: 3.76% (95% CI 2.62-5.35) for Shamblin I CBTs, 14.14% (95% CI 11.94-16.68) for Shamblin II, and 17.10% (95% CI 14.82-19.65) for Shamblin III tumours. The prevalence of neck haematoma requiring re-exploration was 5.24% (95% CI 3.45-7.91). The proportion of patients with a neck haematoma requiring re-exploration was not reduced by pre-operative embolisation (5.92%; 95% CI 2.56-13.08) vs. no embolisation (5.82%; 95% CI 2.76-11.88). Pre-operative embolisation did not reduce drainage losses (639 mL vs. 653 mL).
CONCLUSIONS: This is the largest meta-analysis of outcomes after CBT excision. Procedural risks associated with tumour excision were considerable, especially with Shamblin III tumours where 4% suffered a peri-operative stroke and 17% suffered a CNI.
Retroperitoneal Pelvic Solitary Fibrous Tumor With High Tracer Uptake in 68Ga-DOTATOC PET/CT: A Rare Differential Diagnosis of Paraganglioma.
Clin Nucl Med. 2019; 44(5):e370-e371 [PubMed] Related Publications
COPPS, a composite score integrating pathological features, PS100 and SDHB losses, predicts the risk of metastasis and progression-free survival in pheochromocytomas/paragangliomas.
Virchows Arch. 2019; 474(6):721-734 [PubMed] Related Publications
Hyponatremic-Hypertensive Syndrome in Ovarian Paraganglioma.
Indian Pediatr. 2019; 56(1):69-71 [PubMed] Related Publications
CASE CHARACTERISTICS: A 10-year- old girl presented with polyuria, polydipsia, hypertension, hyponatremia, hypokalemia and proteinuria. Ultrasonography with doppler study revealed bilateral normal renal arteries. Completed tomography of abdomen detected a left adnexal mass, which was later confirmed as ovarian paraganglioma on histopathology.
OUTCOME: After tumor excision, polyuria subsided and blood pressure normalized.
MESSAGE: Hyponatremic-Hypertensive Syndrome does not always result from unilateral renal artery stenosis. High index of clinical suspicion with appropriate imaging technique may clinch rare endocrine causes of hypertension, like paraganglioma.
Colorimetric detection of normetanephrine, a pheochromocytoma biomarker, using bifunctionalised gold nanoparticles.
Anal Chim Acta. 2019; 1056:146-152 [PubMed] Related Publications
Effect of the nervous system on cancer: Analysis of clinical studies.
Bratisl Lek Listy. 2019; 120(2):119-123 [PubMed] Related Publications
Primary Pulmonary Paraganglioma Revealed by FDG PET/CT.
Clin Nucl Med. 2019; 44(4):e311-e312 [PubMed] Related Publications
Surgical Management of Bilateral Carotid Body Tumors.
Ann Vasc Surg. 2019; 57:187-193 [PubMed] Related Publications
METHODS: A retrospective review of CBTs patients was completed; patient demographics, comorbidities, lesion location, anatomic characteristics, surgical techniques, complications, reinterventions, and other factors that may influence outcomes were evaluated.
RESULTS: A total of 109 patients with CBTs were treated surgically; of these, 8 had bilateral CBTs (7%); the mean age was 56 years, and 7 (87%) were females. Thirteen surgical resections were performed, and in 2 of the cases, the pathology report was malignant (15%). Five were classified as Shamblin I (31%), 5 as Shamblin II (31%), and remaining 6 as Shamblin III (38%). The mean time between the first and second procedure was of 10.7 months. Complications included one case of neck hematoma requiring evacuation and postoperative neurologic complications occurred in three patients (one patient with facial and two with vocal cord palsies). None of the studied individuals had a family history of CBT, and all of them lived in altitude areas higher than 2000 meters above mean sea level (mamsl). The mean tumor size was 3.55 cm and 2.75 cm for right and left CBTs, respectively.
CONCLUSIONS: A better understanding of the clinical characteristics of patients with bilateral CBTs may lead to a more standardized and optimal management with fewer complications and a better quality of life afterward.
Glomuvenous malformations in a young man.
Dermatol Online J. 2018; 24(10) [PubMed] Related Publications
Undiagnosed paraganglioma; A challenge during laparoscopic retroperitoneal resection.
Arch Ital Urol Androl. 2019; 90(4):297-298 [PubMed] Related Publications
CASE REPORT: We present a case of a 36-year-old patient who during oncological follow-up for a previous diagnosis of parotid acinar cell carcinoma was incidentally identified as having an interaortocaval tumour. Following routine preoperative assessment the patient was arranged to undergo a laparoscopic retroperitoneal tumour resection. After minimal tumour manipulation the patient developed cardiac rhythm abnormalities and became hypertensive. The tumour was successfully removed laparoscopically after a cautious inter- aortocaval dissection. Abruptly, prior to extraction of the tumour containing endobag, the patient developed cardiac arrest. Following 35 minutes of life support measures there was a return of spontaneous circulation. The endobag was laparoscopically removed from the abdominal cavity 24 hours later using the initial operative port sites. The patient´s progression was satisfactory and he could be discharged six days postoperatively.
CONCLUSIONS: Asymptomatic undiagnosed paragangliomas represent a real challenge during laparoscopic operations. Haemodynamic changes and life-threatening events can arise acutely intraoperatively, where an immediate and coordinated response of the whole theatre team may be required to avoid fatal outcome.
Radiotherapy for parapharyngeal space tumors.
Am J Otolaryngol. 2019 Mar - Apr; 40(2):289-291 [PubMed] Related Publications
Pheochromocytoma presenting with severe hyperglycemia and metabolic acidosis following intra-articular glucocorticoid administration: a case report.
J Med Case Rep. 2019; 13(1):3 [PubMed] Free Access to Full Article Related Publications
CASE PRESENTATION: A 45-year-old Japanese man presented to our hospital with a sudden, severe headache. He had no history of diabetes. He had received an intra-articular injection of betamethasone (2 mg) for joint pain, 2 days prior to his admission. On examination, his blood pressure was 240/126 mmHg and pulse was 120 beats/minute. The possibility of cerebrovascular events was ruled out by imaging studies and lumbar puncture. Blood tests revealed severe hyperglycemia (523 mg/dL) and metabolic acidosis (pH 7.21, anion gap 26.2 mEq/L, lactate 11.75 mmol/L) with a glycosylated hemoglobin level of 5.7%. Although a urine sample could not be obtained, fulminant type 1 diabetes mellitus and diabetic ketoacidosis were suspected based on these findings. However, after the initial treatment for diabetic ketoacidosis, his insulin secretion was found to be normal and the plasma levels of ketones were not elevated. This excluded the possibility of fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Subsequently, a left adrenal gland tumor and elevated levels of serum catecholamine and urinary catecholamine metabolites were detected, while his other hormone levels were normal. Serum catecholamine levels did not decrease following the clonidine test, and a functional scintigraphy using iodine-131 metaiodobenzylguanidine showed strong uptake in the region of the left adrenal gland. Although no signs of pheochromocytoma crisis, such as paroxysmal hyperglycemia and hypertension, had been observed since admission, a pheochromocytoma was diagnosed based on the investigations. After controlling his blood pressure, a left adrenalectomy was performed.
CONCLUSIONS: This case illustrates that intra-articular glucocorticoid administration can induce a pheochromocytoma crisis and an increase in hyperglycemia, and that pheochromocytoma crisis can resemble the clinical picture of fulminant type 1 diabetes mellitus owing to severe hyperglycemia with metabolic acidosis and normal glycosylated hemoglobin levels, especially under the influence of glucocorticoid.
Pleuropulmonary tuberculosis with spinal lesions due to metastatic malignancy differentiated definitively on imaging.
BMJ Case Rep. 2018; 11(1) [PubMed] Related Publications
Extra-adrenal pheochromocytoma presenting as inverse takotsubo-pattern cardiomyopathy treated with surgical resection.
BMJ Case Rep. 2018; 11(1) [PubMed] Related Publications
Building a Competing Endogenous RNA Network to Find Potential Long Non-Coding RNA Biomarkers for Pheochromocytoma.
Cell Physiol Biochem. 2018; 51(6):2916-2924 [PubMed] Related Publications
METHODS: A total of 183 PCC samples and 3 control samples from The Cancer Genome Atlas database were analyzed. The Empirical Analysis of Digital Gene Expression Data package in R (edgeR) was used to analyze differentially expressed RNAs. Biological processes and pathways functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. LncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.0 software based on the differentially expressed RNAs Survival package in R was used to perform survival analysis.
RESULTS: In total, 554 differentially expressed lncRNAs, 1775 mRNAs and 40 miRNAs were selected for further analysis. Subsequently, 23 lncRNAs, 22 mRNAs, and 6 miRNAs were included in the constructed ceRNA network. Meanwhile, two of the 23 lncRNAs (C9orf147 and BSN-AS2) were identified as independent predictors of overall survival in PCC patients (P< 0.05).
CONCLUSION: This study improves the understanding of lncRNA-related ceRNA networks in PCC and suggests that the lncRNAs C9orf147 and BSN-AS2 could be independent prognostic biomarkers and potential therapeutic targets for PCC.
Differences in the actions of adrenaline and noradrenaline with regard to glucose intolerance in patients with pheochromocytoma.
Endocr J. 2019; 66(2):187-192 [PubMed] Related Publications
KTP-laser-assisted endoscopic management of glomus tympanicum tumors: A case series.
Ear Nose Throat J. 2018; 97(12):399-402 [PubMed] Related Publications
Primary malignant tumors of the adrenal glands.
Clinics (Sao Paulo). 2018; 73(suppl 1):e756s [PubMed] Free Access to Full Article Related Publications
Risk factors for postoperative cardiovascular morbidity after pheochromocytoma surgery: a large single center retrospective analysis.
Endocr J. 2019; 66(2):165-173 [PubMed] Related Publications