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Pheochromocytoma and paraganglioma are neuroendocrine tumors characterized by a catecholamine production potential. The biochemical diagnosis for this type of tumor is carried out through the metanephrine titration on 24-hours urines. Some authors have suggested that the sensitivity of the test could be improved by sampling and analyzing urines 3 days in a row (cycle) versus a unique measurement but this method has never been fully evaluated. The goal of this study was to establish a comparison of diagnosis performances between urinary metanephrines measurement for 3 consecutive days, and metanephrines measurement on a unique 24-hour sample. Patients of Brest Regional University Hospital whose 3-consecutive day 24-hour urine samples had been analyzed from January 2011 to May 2017 were included in this study. The primary endpoint was the comparison of diagnostic performances of urinary metanephrine titration over a single day versus 3 consecutive days. Eighty-two patients for a total of 103 cycles among which 7 revealed a pheochromocytoma were analyzed. ROC curve analysis shows that the metanephrine cycle titration method is more efficient than the metanephrine single titration method (metanephrine: AUC=0.881 against 0.826 respectively; normetanephrine: AUC=0.946 against 0.901 respectively). Urinary titration over 3 days allows the diagnosis of 100% (7/7) of pheochromocytomas against 85.7% (6/7) for the the single urinary titration. In conclusion, metanephrine titration over 3 consecutive days of 24-hours urine samples shows a better sensitivity and better diagnosis performances for detecting pheochromocytoma and paraganglioma than the single titration method.

Objective: evaluate the assay of urinary metanephrines in diagnosis of pheochromocytoma (PH) and determine diagnostic cut-off values., Methods: this is a retrospective study about 87 patients suspected of pheochromocytoma,whose of 24-h urinary fractionated metanephrine was measured. These cases were collected from Internal Medecine Departments (A and B) at Charles Nicolle's Hospital. Two groups of patients were studied: a pheochromocytoma group (n=33) with a histologically-proven pheochromocytoma and a control group of 54 patients. Receiver Operating Characteristic (ROC) curves were used to determine the best sensitivities and specificities., Results: The analysis of biological parameters showed that means and standard deviation of urinary fractionated metanephrines in pheochromocytoma group were significantly higher than those of control group. Sensitivity and specificity of urinary normetanephrine test (95% and 98.1% respectively) were higher than those of urinary metanephrine and 3-methoxytyramine. A correlation between urinary normetanephrine and tumor size of pheochromocytoma was found., Conclusion: Urinary fractionated metanephrines is an efficient biochemical test for the diagnosis of pheochromocytoma.

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not established on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3 cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (<10 housefield units) on adrenal tomography. Addison's disease is a pathology affecting about 1 in 8000. Immunopathology is still unknown, but some elements advocated the hypothesis of a predominant cell-mediated immunity in particular Interferon-gamma production by CD4 T lymphocytes in the presence of an epitope from the 21-hydroxylase, as well as IgG1 subtype produced by activated B lymphocytes, autoantibodies do appear to be a simple marker of the disease. Subclinical Addison's disease is defined by the presence of anti-21-hydroxylase autoantibodies, without clinical symptoms. It evolves faster to the clinical phase in young subjects, male, having high levels of autoantibodies and with an initially impaired adrenal function. Dosage of ACTH, plasma renin active, and basal cortisol and after Synacthen allow to discriminate the subjects with low or high risk of evolution and establish an appropriate monitoring., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Paragangliomas are rare tumors arising from extraadrenal chromaffin cells. We report a 43-year-old man who presented with abdominal pain. An abdominal computed tomography scan revealed a large retroperitoneal mass. During an endoscopic biopsy of this tumor, the patient experienced marked hemodynamic fluctuations with tachycardia and high blood pressure, and an extraadrenal pheochromocytoma was suspected. Measurements of plasma and urinary catecholamines and urinary total metanephrines ruled in the diagnosis. Echocardiography disclosed acute myocardial dysfunction that returned to normal after surgical resection of the paraganglioma. This report also underlines the importance of the anesthetic preparation and monitoring around the surgical procedure and the need of a long-term follow-up to detect malignant paraganglioma in the absence of histological criteria of benign tumor., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Adrenal tumors diagnosed after work-up of an incidentaloma can be responsible for excessive secretion of steroids or catecholamines. On the other hand, an infiltrative process (metastases, infection...) involving both adrenals can cause adrenal insufficiency. Clinical and biological work-up is performed to detect hormonal imbalances requiring treatment, and further characterize the nature of the lesion. Screening for pheochromocytoma should be systematic with metanephrine assays on urine or plasma. Screening for cortisol secreting tumors, often responsible for Cushing's syndrome of moderate severity (pre-clinical) in patients with incidentaloma, will be performed using the overnight dexamethasone suppression test (1 mg). Depending on results from the imaging and clinical work-up, excessive secretion of aldosterone, androgens or steroid precursors may sometimes be investigated. In patients with bilateral incidentalomas, the normal synacthen test and ACTH assay are also performed to exclude adrenal insufficiency.

Pheochromocytoma is a rare tumor responsible for paroxysmal hypertension which is difficult to control. Diagnosis is important because it represents a curable form of hypertension. Few cases of pheochromocytoma patients with end-stage renal failure were reported in the literature. These cases are specially responsible for diagnosis and therapeutic problems. We report here a case of an end-stage renal failure patient who has pheochromocytoma, he was treated by automated peritoneal dialysis. The patient is a 47-year-old man who has an IgA glomerulonephritis. On peritoneal dialysis, his blood pressure level remains high despite four antihypertensive drugs association and adequate dialysis. Furthermore, the patient suffered from headaches, sweats and palpitations. This leads to suspect pheochromocytoma. Thus, urinary excretion rates of metanephrines and normetanephrines were high. Radiographic diagnosis tests were negative but MIBG scintigraphy was able to localise the tumor in the left suprarenal gland. He had coelioscopic left adrenalectomy without complications, microscopic studies showed an hyperplasia of the adrenal medulla. Soon after surgery his blood pressure was well controlled by one antihypertensive drug. We conclude that refractory hypertension, as a possible diagnosis, is uncommon in peritoneal dialysis patients. Pheochromocytoma must be eliminated by careful evaluation.

Introduction: The paraganglioma is a rare tumour that can sometimes develop near to the pancreatic gland and can occasionally mimic an intra pancreatic mass. Invasive investigations with puncture or primary surgical resection must be avoided because of the risk of vital complications., Exegesis: We report on the case of a 41 years old woman presenting with a mass apparently affecting the pancreatic gland. She also presented with malaises. Paraganglioma was suspected because of the malaises and the blood pressure crises. The diagnosis was permitted by the findings of high urinary metanephrine levels. So the tumour was resected without previous fine needle aspiration and with specific anaesthetic measures. No complication was observed., Conclusion: When a patient presents with a pancreatic mass, physician must carefully take into account the possibility of a paraganglioma particularly when malaises are present.

Guillain-Barré syndrome is an acute demyelinating polyradiculoneuritis usually evolving with rapid, functional recovery. In severely paralysed patients, cranial nerve palsy and autonomic nervous system dysfunctions are common. Lesions of the spinal roots predominate but segmentary demyelination of peripheral nervous system reflects various clinical subtypes. Twelve patients (42,8 p. cent) had clinical dysautonomia. Ten had an increase of urinary methoxylated metabolites. Patients exempt of dysautonomia had normal biological parameters. The elevated level of urinary methoxylated metabolites is statistically correlated to clinical dysautonomia and can be used as a biological marker to monitoring demyelinating polyradiculoneuritis.

Introduction: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests., Current Knowledge and Key Points: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely., Future Prospects and Projects: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect.

A case of secreting, asymptomatic retroperitoneal paraganglioma is presented. Paragangliomas are rare neuroendocrine tumors and the malignant behaviour, higher than pheochromocytomas, is based on metastases or local recurrence. The treatment is complete surgical excision. Radiotherapy and chemotherapy may be used for palliation of symptoms.

Presently, the diagnosis of pheochromocytoma rests upon the determination of urinary catecholamines, and specially metanephrines which offer 100% sensitivity and 97% specificity. The 24 hours urine collection is problematic for practical reasons and patient compliance. Serum metanephrines determination by HPLC (High Performance Liquid Chromatography) avoids these difficulties making the investigation easier. We report the results of serum metanephrine (MN) and normetanephrine (NMN) in 10 patients presenting with a pheochromocytoma histologically confirmed and without renal insufficiency, compared to 18 control healthy subjects, 33 patients suffering from hypertension and 11 patients with terminal renal failure on haemodialysis. The mean value of total metanephrines (MN + NMN) for the patients presenting with a pheochromocytoma is 326 +/- 206 nmol/l (range 76 to 718). In the control group without hypertension this value is 6.8 +/- 2.9 nmol/l (range 0.5 to 10.7) and for the control group with hypertension 25 +/- 27 nmol/l (range 7 to 138). For the patients with renal failure, the mean value is 471 +/- 201 nmol/l (range 188 to 920). Thus total metanephrines serum level values were found higher in the patients with a pheochromocytoma than in those with or without hypertension, but they were not discriminatory when the cases of renal insufficiency were included. CONCLUSION In case of a normal renal function, serum metanephrines determination for the diagnosis of pheochromocytoma gives, above a threshold value of 50 nmol/l, a sensitivity of 100% and a specificity of 94%.

The dosage of urinary catecholamines and their metabolites is a main element of diagnosis in the research of a pheochromocytoma in patients with high blood pressure. The literature reports high values of these compounds in patients treated with labetalol (an alpha/beta-blocker). An analytical interference has been evoked to explain these misleading results, which have not been observed with other beta-blockers. The goal of this work was to look for this eventual analytical interference in the dosage of urinary metanephrine by reversed phase liquid chromatography coupled with electrochemical detection, in patients with high blood pressure. Eighteen hypertensive patients, 52 +/- 14 years old, were included in the study. In 8 patients, a dosage of metanephrine, normetanephrine and creatinine on a 24 hours urine sample was performed before (D1) and 24 hours after (D3) the prescription of labetalol (200 mg twice a day). In the other group, labetalol was not prescribed but dosage was made in the same conditions. Urinary excretion of these compounds (metanephrine+normetanephrine) divided by urinary creatinine was not modified in the treated group (0.16 +/- 0.08 vs 0.14 +/- 0.04), nor in the reference group (0.17 +/- 0.08 vs 0.17 +/- 0.08). This study shows that administration of labetalol in patients with essential hypertension does not interfere with urinary metanephrine and normetanephrine determination after 48 hours of treatment. This implies that research for a pheochromocytoma is possible in patients with hypertension and receiving labetalol, by using reversed phase liquid chromatography coupled with an electrochemical detector for the dosage of urinary metanephrine and normetanephrine.

The measurement of urinary methoxyamines (metadrenaline and normetadrenaline) by a method as selective as possible, is the best test for the biochemical diagnosis of pheochromocytoma. Its diagnostic reliability (99,5 p. 100) is much higher than that of urinary catecholamines (59 p. 100) or VMA (38 p. 100) or plasma catecholamine measurement. Drug interference is reduced. Two or three tests on consecutive days are adequate to establish the diagnostic, even in intermittent secreting tumours.

The diagnostic problem of pheochromocytomas raises two questions: should all hypertensives be routinely investigated for this condition, and what is the best diagnostic method? As this is a rare condition, systematic screening gives a low return; considering the large number of hypertensive patients, it is also costly. On the other hand, as systematic autopsy studies have shown, the missed diagnosis can be serious (especially during pregnancy or surgery). Screening for this condition is proposed when the clinical features are suggestive, in pregnancy, when surgery is undertaken in a hypertensive patient and in all cases of method is still a matter of controversy: urinary hormonal levels (especially metanephrine levels) are supported by some workers, whilst serum catecholamine levels are supported by others. In any case, pharmacodynamic tests should only be used when these two methods are inconclusive. The long term prognosis of operated pheochromocytoma is less favourable then used to be thought: a certain number have persistent benign hypertension which may require treatment and which may become malignant at a later date. Adrenal medullary hyperplasia is a clinical entity which should be recognised.

The biochemical diagnosis of pheochromocytoma is essentially based on the plasma and urinary levels of catecholamines and their derivatives, the metanephrines and vanyl-mandelic acid. The advantages and disadvantages of these investigations are reviewed, especially as regards the specificity and sensitivity of each test. The measurement of urinary metanephrine is the best test as its excretion is relatively higher, and it is rarely normal. The measurement of plasma catecholamines is more difficult but gives satisfactory results, but experience so far is limited.