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Endocrine Regulations Jul 2019Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of... (Review)
Review
Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of pheochromocytomas carry germline or somatic gene mutations, which are inherited in the autosomal dominant way. All patients should undergo genetic testing. Symptoms are due to catecholamines over production or to a mass effect. Diagnosis is confirmed by raised plasma or urine metanephrines or normetanephrines. Radiology assists in the tumor location and any local invasion or metastasis. All the patients should have preoperative preparation with α-blockers and/or other medications to control hypertension, arrhythmia, and volume expansion. Surgery is the definitive treatment. Follow up should be life-long.
Topics: Adrenal Gland Neoplasms; Adult; Child; Female; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans; Male; Pheochromocytoma; Pregnancy
PubMed: 31517632
DOI: 10.2478/enr-2019-0020 -
Indian Journal of Endocrinology and... 2015Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL...
BACKGROUND
Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL secrete either catecholamine or their metabolites, metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and metanephrine (MN) for the diagnosis of PHEO/PGL.
MATERIALS AND METHODS
Sixty-five patients referred to endocrine/ENT clinics were enrolled. Twelve patients with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients (39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14 patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age- and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN were measured using high-performance liquid chromatography. Receivers operating characteristics was plotted and cut-off levels were established.
RESULTS
When compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in 3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL, there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-, 6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in combination with MN was high in 97% of the patients with PHEO/PGL. All three metabolites in combination were high in 83% of patients with HNPGL. In malignant PHEO/PGL, 50% subjects had increased levels of both NM and 3MT.
CONCLUSIONS
Measurement of plasma-free NM along with 3MT and MN provides a better tool for the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT can be used for the diagnosis of malignant PHEO/PGL.
PubMed: 26425473
DOI: 10.4103/2230-8210.163183 -
Journal of Veterinary Internal Medicine 2013Measurement of plasma-free metanephrines is the test of choice to identify pheochromocytoma in human patients.
BACKGROUND
Measurement of plasma-free metanephrines is the test of choice to identify pheochromocytoma in human patients.
OBJECTIVES
To establish the sensitivity and specificity of plasma-free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.
ANIMALS
Forty-five client-owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)
METHODS
A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS
Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73-175.23] nmol/L) than in healthy dogs (0.95 [0.68-3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25-2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41-6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19-190.31] nmol/L) than in healthy dogs (2.54 [1.59-4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30-10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92-5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%.
CONCLUSIONS AND CLINICAL IMPORTANCE
Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma-free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Metanephrine; Normetanephrine; Pheochromocytoma; Sensitivity and Specificity
PubMed: 23311717
DOI: 10.1111/jvim.12009 -
Endocrinology and Metabolism (Seoul,... Jun 2021Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological...
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated.
METHODS
This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group.
RESULTS
Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity.
CONCLUSION
Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.
Topics: Adrenal Gland Neoplasms; Humans; Metanephrine; Paraganglioma; Pheochromocytoma; Retrospective Studies; Sensitivity and Specificity
PubMed: 34107605
DOI: 10.3803/EnM.2020.925 -
Frontiers in Oncology 2022To analyze the correlation between metanephrine and normetanephrines (MNs) and subclinical myocardial injuries (SMI) diagnosed by low left ventricular...
OBJECTIVE
To analyze the correlation between metanephrine and normetanephrines (MNs) and subclinical myocardial injuries (SMI) diagnosed by low left ventricular global longitudinal strain (LV GLS) in patients with pheochromocytoma and paraganglioma (PPGL).
METHODS
Seventy-six patients who underwent surgery for pheochromocytoma or paraganglioma from September 2017 to April 2022 were examined. All the patients enrolled had normal left ventricular ejection fraction (LVEF) and myocardial injury biomarkers including cardiac troponin I and B-natriuretic peptide. Univariate analysis and multivariate analysis were performed to evaluate the association of MNs and subclinical myocardial injury (SMI)(defined as LV GLS<18).
RESULTS
LV GLS of 13(17.11%) PPGL patients was less than 18. The percentage of patients with elevation of single hormone (metanephrine, normetanephrine, 3-methoxytyramine) or any one of MNs was not significantly correlated with SMI (P=0.987, 0.666, 0.128 and 0.918, respectively). All MNs elevation was associated with SMI (OR: 11.27; 95% CI, 0.94-135.24; P= 0.056). After adjusting for age, All MNs elevation was significantly correlated with SMI (OR: 16.54; 95% CI, 1.22-223.62; P= 0.035).
CONCLUSION
MNs might be an important factor influencing myocardial function. All MNs elevation might indicate SMI. If all MNs elevated, LV GLS measurement was recommended for PPGL patients to detect SMI in the absence of decrease LVEF or other heart disease in clinical practice.
PubMed: 36237312
DOI: 10.3389/fonc.2022.1024342 -
Clinica Chimica Acta; International... Mar 2019Plasma or urinary metanephrines are recommended for screening of pheochromocytomas and paragangliomas (PPGLs). Measurements of urinary free rather than deconjugated...
BACKGROUND
Plasma or urinary metanephrines are recommended for screening of pheochromocytomas and paragangliomas (PPGLs). Measurements of urinary free rather than deconjugated metanephrines and additional measurements of methoxytyramine represent other developments. For all measurements there is need for reference intervals.
METHODS
Plasma free, urinary free and urinary deconjugated O-methylated catecholamine metabolites were measured by LC-MS/MS in specimens from 590 hypertensives and normotensives. Reference intervals were optimized using data from 2,056 patients tested for PPGLs.
RESULTS
Multivariate analyses, correcting for age and body surface area, indicated higher plasma and urinary metanephrine in males than females and sex differences in urinary normetanephrine and free methoxytyramine that largely reflected body size variation. There were positive associations of age with plasma metabolites, but negative relationships with urinary free metanephrine and methoxytyramine. Plasma and urinary normetanephrine were higher in hypertensives than normotensives, but differences were small. Optimization of reference intervals using the data from patients tested for PPGLs indicated that age was the most important consideration for plasma normetanephrine and sex most practical for urinary metabolites.
CONCLUSION
This study clarifies impacts of demographic and anthropometric variables on catecholamine metabolites, verifies use of age-specific reference intervals for plasma normetanephrine and establishes sex-specific reference intervals for urinary metabolites.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Chemical Analysis; Chromatography, Liquid; Dopamine; False Positive Reactions; Female; Humans; Hydrolysis; Male; Metanephrine; Middle Aged; Normetanephrine; Reference Values; Sex Characteristics; Tandem Mass Spectrometry; Young Adult
PubMed: 30571948
DOI: 10.1016/j.cca.2018.12.019 -
Biochemia Medica Jun 2020Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater...
Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater sensitivity and specificity than catecholamines for pheochromocytoma detection. This case highlights the preanalytical factors which can influence metanephrine measurement and cause a false positive result. It describes a patient with a high pre-test probability of pheochromocytoma due to hypertension and a past medical history of adrenalectomy for a purported pheochromocytoma in her home country. When biochemical screening revealed grossly elevated urine normetanephrine in the presence of a previously identified right adrenal lesion, there was high clinical suspicion of a pheochromocytoma. However, functional imaging did not support this view which prompted additional testing with plasma metanephrines. Results for plasma and urine metanephrines were discordant and preanalytical drug interference was suspected. Patient medications were reviewed and sulfasalazine, an anti-inflammatory drug was identified as the most likely analytical interferent. Urinary fractionated metanephrines were re-analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and all metanephrines were within their reference intervals. This case illustrates how method-specific analytical drug interference prompted unnecessary expensive imaging, heightened patient anxiety and resulted in lengthy investigations for what turned out to be a phantom pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Chromatography, Liquid; Chromogranin A; False Positive Reactions; Female; Humans; Hypertension; Medical Errors; Metanephrine; Middle Aged; Pheochromocytoma; Sulfasalazine; Tandem Mass Spectrometry; Urinalysis
PubMed: 32550819
DOI: 10.11613/BM.2020.021003 -
Endocrine Connections Oct 2020177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We...
INTRODUCTION
177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL.
METHODS
This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy.
RESULTS
A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11-62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity.
CONCLUSION
177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.
PubMed: 32784267
DOI: 10.1530/EC-20-0292 -
Physiological Research Sep 2017This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for...
This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Biomarkers, Tumor; Chromogranin A; Female; Humans; Male; Metanephrine; Middle Aged; Normetanephrine; Pheochromocytoma; Radioimmunoassay; Young Adult
PubMed: 28948824
DOI: 10.33549/physiolres.933719 -
Journal of Veterinary Internal Medicine Jan 2023Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs).
BACKGROUND
Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs).
HYPOTHESIS/OBJECTIVES
To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI).
ANIMALS
Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs.
METHODS
Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively.
RESULTS
The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99).
CONCLUSIONS AND CLINICAL IMPORTANCE
With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.
Topics: Dogs; Animals; Metanephrine; Pheochromocytoma; Chromatography, Liquid; Retrospective Studies; Tandem Mass Spectrometry; Normetanephrine; Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Dog Diseases
PubMed: 36637037
DOI: 10.1111/jvim.16624