Eu ropea n. Journal of. En docrino logy. Clinical Study. A Riester and others. Life- threatening events in pheochromocytoma. – Pheochromocytomas vary in presentation, tumor size, and in catecholamine production. Whether pheochromocytoma size correlates with hormone levels. The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 6, . Definition of pheochromocytoma and paraganglioma (PPGL).

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Young; Pheochromocytoma and Paraganglioma: The aim was to formulate clinical practice guidelines for pheochromocytoma jurjal paraganglioma PPGL. The authors received no corporate funding or remuneration. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation GRADE system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews.

One group meeting, several conference calls, and e-mail communications enabled consensus. The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines.

Consideration should be given to preanalytical factors leading to false-positive or false-negative results.

Case Report: Pheochromocytoma: clinical review based on a rare case in adolescence

All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications.

Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. pheochrompcytoma

Pheochromocytoma: clinical review based on a rare case in adolescence

We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.

Specifically, pretest and post-test counseling should be available. All tests for PPGL genetic testing should be performed by accredited laboratories. Treatment should also include a high-sodium diet and fluid intake to reverse catecholamine-induced blood volume contraction preoperatively pheochromocutoma prevent severe hypotension after tumor removal.

We suggest lifelong annual biochemical testing to assess for recurrent or metastatic disease. In particular, patients should be referred to such centers should there be pregnancy, metastatic disease, or issues concerning the complexity or difficulty in biochemical diagnosis; localization; performance and interpretation of genetic testing; preoperative preparation; surgical treatment; and follow-up. The Clinical Guidelines Subcommittee CGS of the Endocrine Society deemed the diagnosis of pheochromocytoma and paraganglioma a priority area in need of practice guidelines and appointed a Task Force to formulate evidence-based recommendations.

The Task Force followed the approach recommended by the Grading of Pheochromocytom, Assessment, Development, and Evaluation GRADE group, an international group with expertise in the development and implementation of evidence-based guidelines 1.

A detailed description of the grading scheme has been published elsewhere 2.

The Task Force used the best available research evidence to develop the recommendations. The Task Force also used consistent language and graphic descriptions of both the strength of a recommendation and the quality of evidence. The Task Force has confidence that persons who receive care according to the strong recommendations will derive, on average, more good than harm.

Weak recommendations require more careful consideration of the person’s circumstances, values, and preferences to determine the best course of action. Linked to phecohromocytoma recommendation is a description of the evidence and the values that panelists considered in making the recommendation; in some instances, there are remarksa section in which panelists offer technical suggestions hpeochromocytoma testing conditions, dosing, and monitoring. These technical comments reflect the best available evidence applied to a typical person being treated.

Often this evidence comes from the unsystematic observations of the panelists and their values and preferences; therefore, these remarks should be considered suggestions. The Endocrine Society maintains a rigorous conflict-of-interest review process for the development of clinical practice guidelines.

All Task Force members must declare any potential conflicts of interest, which are reviewed before the members are approved to serve on the Task Force and periodically during the development of the guideline.

The conflict-of-interest forms are vetted by the CGS before the members are approved by the Society’s Council to phheochromocytoma on the guideline Task Force.

Participants in the guideline development must include a majority of individuals without conflict of interest in the matter under study. Participants with conflicts of interest may participate in the development of the guideline, but they must have disclosed all jurnnal. The CGS and the Task Force have reviewed all disclosures for this guideline and resolved or managed all identified conflicts of interest. Conflicts of interest are defined by remuneration in any amount from the commercial interest s in the form of grants; research support; consulting fees; salary; ownership interest eg, stocks, stock options, or ownership interest excluding diversified mutual funds ; honoraria or other payments for participation in speakers’ bureaus, advisory boards, or boards of directors; or other financial benefits.


Completed forms are available through the Endocrine Society office. Funding for this guideline was derived solely from the Endocrine Society, and thus the Task Force received no funding or remuneration from commercial or other entities. A pheochromocytoma is a tumor arising from adrenomedullary chromaffin cells that commonly produces one or more catecholamines: Rarely, these tumors are biochemically silent. A paraganglioma is a tumor derived from extra-adrenal chromaffin cells of the pheochromochtoma paravertebral ganglia of thorax, abdomen, and pelvis.

Paragangliomas also arise from parasympathetic ganglia located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull 3 ; these do not produce catecholamines. These last paraganglioma in the neck and at the base of the skull receive minimal coverage in this guideline.

Together they will be referred to here as PPGL. The prevalence of PPGL in patients with hypertension in general outpatient clinics varies between 0. Diagnosis of PPGL may be missed during life; autopsy studies demonstrate undiagnosed tumors in 0. In children with hypertension, the prevalence of PPGL is approximately 1.

At least one-third of all patients with PPGLs have disease-causing germline mutations inherited mutations present in all cells of the body. Patients with hereditary PPGLs typically present with multifocal disease and at a younger age than ;heochromocytoma with sporadic neoplasms 15 It is important to suspect, confirm, localize, treat, and resect these tumors for several reasons.

Biochemical Diagnosis of Pheochromocytoma, a Rediscovered Catecholamine-Metabolizing Tumor

Most of these tumors hypersecrete catecholamines, and if untreated, cardiovascular morbidity and mortality are high 17 — Also, PPGLs enlarge with time and may cause mass-effect symptoms by encroaching upon or extending into adjacent tissues and pheochromocytoms. Another reason to encourage case detection is that, for familial disease, detection of a tumor in the proband may result in earlier diagnosis and treatment in other family members.

Finally, some PPGLs have malignant potential. The most important step for diagnosis of PPGL is to first recognize the possibility of the tumor.

As reviewed in detail elsewhere 472526it is key to recognize the signs and symptoms and other manifestations or clinical settings that might signal a need for biochemical testing for PPGL Tables 1 and 2. Biochemical testing is also warranted in syndromic forms of PPGL, jurnsl may be indicated by specific clinical stigmata Table 3.

There is compelling evidence that measurements of plasma free or urinary fractionated metanephrines are superior to other tests of catecholamine excess for diagnosis of PPGLs; the theoretical basis for this is provided by improved understanding of catecholamine metabolism 27 — According to this understanding, the free metanephrines are produced within adrenal chromaffin cells or the tumors derived from these cells by membrane-bound catecholamine O -methyltransferase.

Lack of this enzyme in sympathetic nerves, the major site of initial norepinephrine metabolism, means that the O -methylated metabolites are relatively specific markers of chromaffin tumors. Most importantly, these metabolites are produced continuously within tumors by a process that is independent of exocytotic catecholamine release, which for some tumors occurs at low rates or is episodic in nature.

The superior sensitivity of urine metanephrines over catecholamines and vanillylmandelic acid VMA for diagnosis of PPGLs was first suggested from a meta-analysis by Manu and Runge This analysis was followed by reports revealing false-negative results for measurements of urine catecholamines and VMA and improved accuracy with measurements of urinary metanephrines 31 — Initial evidence that measurements of plasma free metanephrines provide advantages for diagnosis of PPGLs over other tests was first outlined by Lenders et al Diagnostic specificity was equivalent to other tests, but diagnostic sensitivity was superior.

The final NIH report, with cumulative experience in over patients, established that the superiority of plasma metanephrines for the diagnosis remained significant, even when compared with combinations of other tests The high diagnostic accuracy of measurements of plasma free metanephrines has now been confirmed by 15 independent studies 39 — 53 Table 4. Areas under receiver operating characteristic ROC curves reported in nine of these studies ranged from 0.

These exceptions included one study in which the combination of urinary catecholamines and total metanephrines normetanephrine and metanephrine measured in combined form by spectrophotometry was assessed by areas under ROC curves to offer similar diagnostic accuracy to measurements of plasma metanephrines Five of the 15 studies involved comparisons of plasma free with urine fractionated metanephrines 39424648 The results suggest higher specificity of the plasma than the urine test Table 5 ; however, all five studies had limitations, and none involved head-to-head comparisons of mass spectrometric-based measurements.


Data restricted to that available from Table 4 of those studies where all measurements were made. This includes measurements of urinary free fractionated metanephrines as an alternative test 55 — Thus, all measurements of fractionated metanephrines remain recommended as initial screening tests.

The committee recognizes the importance of high diagnostic sensitivity as a primary consideration to avoid missed diagnoses of potentially lethal tumors and the need to minimize additional testing eg, imaging when initial test results are negative.

Our recommendation that initial testing should always include measurements of plasma free or urinary fractionated metanephrines does not exclude the use of additional biochemical tests during initial testing. Despite the convenience of a spot urine sample, there is no evidence to suggest that this should replace the standardized hour urine collection method.

When measuring the hour urinary excretion of fractionated metanephrines, urinary creatinine should be measured to verify completeness of the urine collection.

Pheochromocytoma and Paraganglioma – Endotext – NCBI Bookshelf

Accumulating evidence indicates that the diagnostic performance of these methods varies to an extent that this should be considered in the choice of diagnostic tests. These data reveal lower diagnostic sensitivity of the latter than the former measurement methods.

The committee recognizes that the availability of different measurement methods varies regionally. Therefore, our recommendation that the choice of biochemical test for diagnosis of PPGL should take into account the method of measurement pertains mainly to locations where there is a choice in available methods.

Where choice is limited, consideration should be given to upgrading to more accurate and precise measurement methods or referring patients or specimens to specialist centers where such methods are available. Measurements of plasma metanephrines for diagnosis of PPGLs were established using blood samples collected in the supine position; this recognizes the rapid circulatory clearances of the metabolites, the strong influence of sympathetic activation and upright posture to stimulate release of norepinephrine and metabolism to normetanephrine, and likely the lack of response in patients with PPGLs 37 — 3960 Lack of response of plasma normetanephrine to upright posture in patients with PPGLs was confirmed by Raber et al 40but was misinterpreted to support sampling without consideration of postural or other influences on sympathetic outflow and plasma normetanephrine 62 Recognizing the problem of seated sampling, Lenders et al 64 took blood samples from 60 patients with primary hypertension in the seated position and after 30 minutes of supine rest, at which stage consistent decreases in plasma normetanephrine were noted.

Using data from a further patients tested for PPGLs, it was calculated that drawing blood in the seated position would result in a 2.

Higher concentrations of plasma metanephrines in upright positions of blood sampling than in supine positions have been confirmed in other studies 6566explaining why upper cutoffs of reference intervals determined from blood collected in the seated position 48626367 are up to 2-fold higher than those determined in the supine position Thus, in the study by Lenders et al 64it was estimated that the use of upper limits of reference intervals determined from samples collected in the seated instead of the supine position would result in a drop in diagnostic sensitivity associated with a 3-fold increase in false-negative results.

Because patients with PPGLs do not show significant posture-associated increases in metanephrines 40the associated danger of missing the diagnosis with seated jufnal intervals applies equally to patients sampled in both supine and seated positions. The potential for misdiagnoses associated with seated rather than supine sampling is evident from examination of data available from five and seven respective pheocrhomocytoma involving supine and seated sampling Table 4in which seated sampling is associated with reduced diagnostic accuracy.

It is therefore suggested that for diagnosis of PPGLs, blood should be preferably taken with the patient in the supine position; when blood jurnak in the seated position yields a positive result, the test should be repeated in the supine position. Furthermore, for interpretation of results, reference intervals should be utilized that do not compromise diagnostic sensitivity. Age adjustments for upper cutoffs to both maintain diagnostic sensitivity and minimize false-positives associated with higher plasma concentrations of normetanephrine in older patients provide one approach The committee recognizes that at most clinical centers, phlebotomists routinely sample blood with patients in the seated position.

Sampling in the supine position takes extra time and effort and entails additional cost.