Pheochromocytoma: 1926–1993

doi:10.1016/1043-2760(93)90035-D

Trends in Endocrinology & Metabolism

Volume 4, Issue 4, May–June 1993, Pages 122-127

https://doi.org/10.1016/1043-2760(93)90035-D Get rights and content

Abstract

Pheochromocytoma is a tumor frequently sought and rarely found. It is associated with spectacular cardiovascular disturbances and, when correctly diagnosed and properly treated, it is curable; when undiagnosed or improperly treated, it can be fatal. Catecholamine-producing tumors that arise from chromaffin cells of the adrenal medulla and sympathetic ganglia are termed pheochromocytomas and paragangliomas, respectively. However, the term pheochromocytoma has become the generic name for all catecholamine-producing tumors. The biochemical diagnosis is straightforward. The localization of pheochromocytoma has been greatly facilitated by advances in computerized imaging and meta-iodobenzylguanidine scanning. Treatment with preoperative α- and β-adrenergic blockade followed by surgical excision of the pheochromocytoma are associated with very low morbidity and mortality.

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Cited by (53)

Pitfalls in the diagnosis and follow-up of a giant pheochromocytoma
2022, Journal of Clinical and Translational Endocrinology: Case Reports
Citation Excerpt :
Catecholamine-secreting tumors should be suspected in the following contexts: adrenergic paroxysms, treatment-resistant arterial hypertension or hypertension in young patients, a family history of MEN 2A or 3, neurofibromatosis or von Hippel–Lindau syndrome, adrenal incidentaloma, shock or severe blood pressure responses during surgery with anesthetic induction and invasive procedures, and idiopathic dilated cardiomyopathy. The catecholamine-secreting tumor assessment and treatment flowchart described by Young Jr. (1993) [8] and corroborated in subsequent studies were followed for the diagnostic workup of the reported case. Patients must stop taking medications that can influence biochemical assessment results (e.g., tricyclic drugs and muscle relaxers), as well as avoid taking actions/eating food types capable of changing them 2 weeks before the tests.
We report the case of a giant pheochromocytoma, which was a composite tumor, a very rare pathology accounting for only 3% of pheochromocytomas.
A 61-year-old male patient presented with paroxysms: palpitation episodes, headache, and spells of elevated blood pressure (BP) for 4 years, as well as nocturnal diaphoresis, chronic diarrhea, and weight loss. The 24-h urine analysis showed a marked increase in normetanephrines and metanephrines. Computed tomography (CT) showed massive heterogeneous solid-cystic expansive formation with septations and areas showing soft tissue density. MIBG-iodine 131 had an extensive, rounded, heterogeneous hyper-uptake lesion in the left upper abdominal region, which measured 16.9 cm at its largest diameter. Finally, magnetic resonance imaging (MRI) revealed a massive expansive solid cystic lesion likely originating in the left adrenal gland.
Overall, 90% of patients with catecholamine-secreting tumors present with symptoms, and half have paroxysms. Fractionated metanephrines are one of the most sensitive and specific products released by tumors. Every patient with catecholamine-secreting tumors must undergo resection. Given the high surgical risk, the pre-operative period must be well managed by controlling the patient's blood pressure to avoid a hypertensive crisis during surgery.
Proper pheochromocytoma diagnosis and treatment are important in endocrinology clinical practice because they help avoid sequelae and unexpected outcomes. Special care should be taken to perform a differential diagnosis in patients with elevated blood pressure, such as changing the workup applied to hypertensive patients, a common condition affecting the overall population.
Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma
2022, Endocrine Practice
Citation Excerpt :
Definitive treatment of nonmetastatic disease can be achieved surgically. Preoperative medical management with alpha-adrenergic receptor blockers is recommended for all patients due to the risk of hemodynamic instability and perioperative cardiovascular complications from manipulation and procedure-stimulated catecholamine release during surgery.1-11 Phenoxybenzamine, a nonselective, irreversible alpha-blocker, is the drug of choice for preoperative blockade of pheochromocytoma prior to adrenalectomy; however, alpha-1 selective competitive inhibitors such as doxazosin may be equally effective.
Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine.
We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs.
Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin.
Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.
Preoperative α-blockade in catecholamine-secreting tumours: Fight for it or take flight?
2017, British Journal of Anaesthesia
Evaluating the optimum rest period prior to blood collection for fractionated plasma free metanephrines analysis
2016, Practical Laboratory Medicine
Citation Excerpt :
Our data suggests that more than 30 min rest is not required prior to sampling. In our cohort, only 2.7% of subjects had PPGL and 4.9% were post-resection of PPGL, which confirms that the condition is “frequently sought but rarely found” [28–30]. A patient screened for PPGL at our centre is 36 times more likely to have a negative than a positive screening test.
The high diagnostic accuracy of plasma metanephrines (PMets) in the diagnosis of Phaeochromocytoma/Paraganglioma (PPGL) is well established. Considerable controversy exists regarding optimum sampling conditions for PMets. The use of reference intervals that do not compromise diagnostic sensitivity is recommended. However, the optimum rest period prior to sampling has yet to be clearly established. The aim of this study was to evaluate PMets concentrations in paired blood samples collected following 30 and 40 min seated-rest prior to sampling, in patients in whom it was clinically reasonable to suspect that PPGL may be present.
A retrospective cross-sectional study design was used. PMets results from paired blood samples collected after 30 and 40 min seated-rest between January 2009 and June 2015 were recorded. Results were interpreted using reference intervals established in subjects seated and supine.
A total of 410 patient results were eligible for analysis. There was no statistical difference between plasma normetanephrine (NMN) or metanephrine (MN) concentrations in samples collected following 30 and 40 min seated-rest in subjects with PPGL (n=11), post-resection of PPGL (n=20) or in whom PPGL was excluded (n=379). Using reference intervals established in the seated position, diagnostic sensitivity was 100% at 30 min and 90.9% at 40 min. Diagnostic specificity was approximately 95% at both time points. When supine reference intervals were used, diagnostic sensitivity was 100% and diagnostic specificity was reduced by ≈22% at both time points.
Based on these data, we recommend at most 30 min continuous rest prior to sampling for PMets measurement.
Endocrine Hypertension
2015, Williams Textbook of Endocrinology
Neurologic complications of disorders of the adrenal glands
2014, Handbook of Clinical Neurology
Citation Excerpt :
Other disorders can raise levels of catecholamines and metanephrines, and they should be considered in the interpretation of the tests. These include withdrawal from medications or drugs (e.g., clonidine, alcohol), subarachnoid hemorrhage, migraine headaches, pre-eclampsia, and the use of medications such as tricyclic antidepressants, levodopa, buspirone, prochlorperazine, and acetaminophen (Young, 1993). The clonidine suppression test is highly sensitive to distinguish between pheochromocytoma and other causes of increased plasma catecholamines.
Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing’s syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms.
This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed.

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Trends in Endocrinology & Metabolism

Pheochromocytoma: 1926–1993

Abstract

Endocrinol Metab Clin

Am J Surg

J Urol

Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease

Medicine

Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine

Ann Intern Med

Prognostic significance of nuclear DNA content in phaeochromocytoma

Aust NZ J Surg

Catecholamine-induced cardiomyopathy in multiple endocrine neoplasia: a histologic, ultrastructural, and biochemical study

Chest

Laparoscopic adrenalectomy in Cushing's syndrome and pheochromocytoma [Letter to the editor]

N Engl J Med

Pheochromocytoma and hypertension: an analysis of 207 cases

Int Abstr Surg

Glucagon and clonidine testing in the diagnosis of pheochromocytoma

Hypertension