[2][4][5] These neuroendocrine tumors can be sympathetic, where they release catecholamines into the bloodstream which cause the most common symptoms, including hypertension (high blood pressure), tachycardia (fast heart rate), sweating, and headaches.

[11] Attacks can occur spontaneously (without warning) or may be triggered by a variety of pharmaceutical agents (including histamine, metoclopramide, glucagon[12] and adrenocorticotropic hormone), foods that contain tyramine (cheese and wine), intraoperative tumor manipulation, intubation, or during anesthetic induction.

Furthermore, when pictured in the ideal clinical scenario (an older woman in her mid-50s), the spontaneous attacks of flushing, sweating, and a racing heart may be mistaken for pre-menopausal related hot flashes.

[9] Determining the genetic status of a pheochromocytoma patient is crucial — each gene is inherited in a different pattern, associated with specific disease characteristics, and may respond more favorably to certain treatment options.

Conversations should occur at an individual level with the patient and their provider to develop a personalized screening plan that alternates between a biochemical (blood work) evaluation and whole-body imaging to monitor disease progression.

There is no single histological finding or biomarker to reliably predict metastatic disease, and multiparameter scoring systems have been proposed [62] Elevated plasma free metanephrines is considered the gold standard diagnosis for pheochromocytoma.

[citation needed] Borderline elevated metanephrines present a diagnostic challenge to the physician — the first step is to repeat the labs, taking extra precautions to follow the gold standard diagnosis described above, including the conditions of collection, pharmaceutical interference, and any potential diet and lifestyle habits that could alter the results.

[7][74] In the 1970s, the drug clonidine hydrocloride swept the market as a novel agent for hypertension; however, the reported side-effects (nausea, vomiting, drowsiness, dryness of the eyes and mouth, constipation, and generalized weakness) limit compliance and have vastly diminished prescriptions.

[91] However, further investigation revealed that while MIBG excelled with adrenal lesions, it was far less superior in patients with extra-adrenal paragangliomas, particularly with specific genetic variants like those in the succinate dehydrogenase subunit–encoding genes (SDHx).

[non-primary source needed][102][103] An open procedure (traditional surgical technique) is currently preferred for extra-adrenal disease, unless the tumor is small, non-invasive, and in an easy to maneuver location.

[non-primary source needed][109] In order to help circumvent a catecholamine-crisis, the United States Endocrine Society recommends that all patients with functional (hormonally active) tumors be started on a pre-operative alpha-adrenoceptor blockade a minimum of seven days prior to surgery.

When patients are initially exposed to one of the above agents, they may become lightheaded, dizzy, and nauseous, particularly when transferring from a seated to standing position due to a rapid decrease in blood pressure.

Common side effects include dry mouth, nasal congestion, and impaired male ejaculation, all of which do not cease with time and may limit patient compliance.

[non-primary source needed][114] In 1995, a team of physicians from London described the death of a person who had been recently diagnosed pheochromocytoma after initiation of propranolol, a non-selective beta blocker.

[123] In a 2010 survey of 40 endocrinologists by researchers at the Cedars-Sinai Medical Center in Los Angeles, California, nearly all indicated the importance of preoperative volume resuscitation (having the patient take in plenty of fluids prior to surgery).

It was hypothesized that the providers chose to forego volume repletion in the older patient population for fear of their potential comorbidities (heart failure) where excess fluid is dangerous.

[124] While there is still no recognized consensus or gold standard, providers should individualize the decision based on the patient's perceived nutritional standing, volume status, comorbidities, and ability to self-hydrate.

[135] There have been several studied risk factors associated with the development of metastatic disease — while the patients genetic background plays an important role, the initial age of presentation and size of the tumor lead to negative outcomes.

[142] Reports have also indicated the utility of administering a radionuclide agent like iodine-123 meta-iodobenzylguanadine (123I-MIBG) prior to surgery and then scanning the patient intraoperatively with a probe to detect disease that may be missed with the naked eye.

A team of researchers from the National Institutes of Health reported that patients with succinate dehydrogenase subunit B (SDHB) mutations are not only more likely to initially respond to CVD, but that they also experienced over 30 months of progression-free survival (time until tumor returned) with continued administration.

[164] This is an extremely difficult question when it comes to pheochromocytoma, and the answer depends on the patients genetic status, presence of metastatic disease, and the location of their primary tumor.

[166] In 2019, a consortium of almost twenty European medical centers looked at the prognosis of malignant pheochromocytoma and the data starkly varies from the report of sporadic, single tumors, with a median survival of 6.7 years.

[167] Overall survival improved if the patient had (1) disease of the head and neck compared to abdomen, (2) less than 40 years of age, (3) and if their biochemistry was less than five times the upper reference limit of normal.

[173] Current hypotheses for why the incidence of pheochromocytoma is growing in the Dutch population point to the advent of modern imaging evaluation and the ability to detect these tumors prior to death.

[179][180] While various physicians were recognizing symptoms and treating patients, Czech biologist Alfred Kohn reported his discovery of the paraganglia system, which would later become crucial to the diagnosis of these tumors.

[181] In 1908, two pathologists, Henri Alezais and Felix Peyron, introduced the scientific community to "paraganglioma" after they discovered extra-adrenal tissue that reacted to chromium salts, which mimicked the reaction of the adrenal medulla.

[182] Just four years later, German pathologist Ludwig Pick coined the term "pheochromocytoma" after he observed the consistent color change in tumors associated with the adrenal medulla.

Retrospective series have postulated that these alarmingly high death rates were due to the lack of a pre-operative blockade with alpha and beta-adrenoceptor antagonist and the need for modern anesthesia practices.

In July 2012, an actual pheochromocytoma patient, Tannis Brown, former vice-president of the PheoPara Troopers, was featured on the Discovery Fit & Health Network program Diagnosis: Dead or Alive.

[188] The show highlighted her personal struggle with misdiagnosed disease as many physicians felt her episodic headaches and hypertension (high blood pressure) were related to stress.