Pheochromocytoma

IWBCA
Feb 13
16 min read

Pheochromocytoma is a rare tumor arising from chromaffin cells in the adrenal medulla that overproduce catecholamines, leading to episodes or sustained periods of severe high blood pressure, headaches, palpitations, and other “fight or flight” symptoms; most tumors are benign but a minority are malignant, and targeted evaluation plus surgical removal or other therapies usually provide excellent outcomes when diagnosed in time.

Overview

What is pheochromocytoma?

Pheochromocytoma is a rare tumor that develops in the central portion of one or both adrenal glands, called the adrenal medulla, from hormone-producing chromaffin cells. These cells normally release catecholamines such as epinephrine and norepinephrine to help the body respond to physical or emotional stress. When they become neoplastic, they can release these hormones in bursts or at persistently elevated levels independent of normal control, driving episodes of very high blood pressure, pounding headaches, sweating, palpitations, anxiety, and other features of an exaggerated “fight or flight” response. In most people, the tumor affects a single adrenal gland, but both glands can be involved, and some patients have more than one tumor in the same gland.

Most pheochromocytomas are benign and confined to the adrenal gland, but approximately 10-15% are malignant and metastasize to lymph nodes, bone, liver, lungs, or other distant sites. When malignant, they are classified as localized if limited to the adrenal gland, regional if they involve nearby nodes or tissues, metastatic if they have spread to distant organs, and recurrent if they recur after prior treatment. Because there is no universally accepted staging system, clinicians rely on this descriptive framework, along with imaging and pathology, to guide therapy. Despite their potential seriousness, pheochromocytomas are often very treatable. Careful preoperative blood pressure control followed by surgical removal is the mainstay of management, and timely treatment can prevent life-threatening cardiovascular complications from uncontrolled catecholamine surges.

Anatomy and Physiology

What are adrenal glands and what do they do?

The adrenal glands are small endocrine organs that sit on top of each kidney at the back of the upper abdomen. Each gland contains two functionally distinct regions that work in parallel. The outer adrenal cortex produces steroid hormones, including cortisol, aldosterone, and adrenal androgens. These hormones regulate metabolism, salt and water balance, blood pressure, and aspects of sexual development and maintenance.

The inner adrenal medulla, where pheochromocytomas arise, is composed of chromaffin cells that specialize in rapid hormone release. It produces catecholamines in response to signals from the nervous system and releases them directly into the bloodstream during acute stress. Under normal conditions, the cortex provides background hormonal regulation while the medulla provides short bursts of stress hormones when needed. When a tumor develops in the medulla oblongata, this stress response is no longer appropriately controlled and can impose a sustained, abnormal load on the cardiovascular system.

Catecholamine Hormones

How are catecholamines related to the body's stress response?

Catecholamines are fast-acting hormones that coordinate the body’s immediate response to physical or emotional stress. The adrenal medulla releases epinephrine and norepinephrine, and smaller amounts of dopamine, into the circulation when activated by the nervous system. These hormones increase heart rate and contractility, modulate blood vessel tone across organs, raise blood pressure, and mobilize glucose and other energy sources. They also heighten alertness, creating the familiar “fight or flight” state.

In healthy physiology, catecholamine surges are brief and tightly regulated, rising and falling as the stressor appears and resolves. In pheochromocytoma, tumor cells release catecholamines at inappropriate times or at persistently elevated levels. This can cause sudden blood pressure spikes, severe headaches, heavy sweating, tremors, palpitations, and episodes that resemble panic attacks, or chronic high blood pressure with intermittent severe attacks. Recognizing this pattern as a hormone-driven process allows clinicians to search for and treat the tumor, which can remove the underlying driver and substantially reduce cardiovascular risk.

Related Conditions

What is the difference between pheochromocytoma and paraganglioma?

Pheochromocytomas and paragangliomas both arise from chromaffin cells, the neuroendocrine cells that produce catecholamines. Because they share this origin, they can produce the same hormones, cause similar “adrenaline surge” symptoms, and occur within the same hereditary syndromes.

Pheochromocytoma in the Adrenal Medulla: A pheochromocytoma is defined by its location in the adrenal medulla, the central portion of the adrenal gland sitting on top of the kidney. These tumors are confined to the adrenal glands and are the classic cause of catecholamine-producing adrenal masses, often presenting with episodic or sustained high blood pressure, headaches, sweating, and palpitations.

Paraganglioma Outside the Adrenal Glands: Paragangliomas are closely related tumors that develop outside the adrenal glands along sympathetic or parasympathetic nerve pathways, for example, in the abdomen, chest, neck, or base of the skull. Some secrete catecholamines and mimic adrenal pheochromocytomas clinically; others are hormonally silent and present because of mass effect or imaging findings. The distinction between pheochromocytoma and paraganglioma is therefore anatomical rather than functional.

Implications For Hereditary Risk and Follow-Up: Both pheochromocytomas and paragangliomas can be sporadic or part of hereditary syndromes, and both can behave benignly or malignantly. Because extra-adrenal paragangliomas have a higher likelihood of hereditary association in many series, their presence often triggers broader genetic evaluation and long-term surveillance for additional tumors in the same family of disorders.

Epidemiology

Who is most likely to develop pheochromocytoma and how common is it?

Age Distribution: Pheochromocytomas can occur at any age, but they are most commonly diagnosed in adults aged 30-50 years. This is typically when symptoms or incidental imaging findings bring them to light, although subtle features may have been present for some time before diagnosis.
Children and Adolescents: A smaller proportion of cases, roughly one in ten, occurs in children and adolescents. In younger patients, pheochromocytoma is more likely to be associated with an inherited syndrome, and the presence of severe or labile hypertension in a child should prompt consideration of this diagnosis.
Rarity in the Hypertensive Population: Pheochromocytomas are rare overall, accounting for less than 1% of cases of high blood pressure. Most people with hypertension do not have a pheochromocytoma, but because untreated tumors can cause serious cardiovascular complications, they are an important diagnosis to consider in the right clinical setting.
Underdiagnosis and Asymptomatic Cases: The true frequency of pheochromocytoma is difficult to pin down because some tumors produce few or no symptoms and are discovered only incidentally on imaging or at autopsy. As a result, clinically recognized cases likely represent only a portion of all tumors that occur in the population.

Symptoms and Causes

What are the most common symptoms and underlying causes of pheochromocytoma?

Catecholamine-Driven Symptoms: Symptoms of pheochromocytoma arise when the tumor releases excess epinephrine and norepinephrine into the bloodstream. These hormones drive the body’s “fight or flight” response, so surges can cause abrupt episodes of pounding high blood pressure, intense headache, palpitations, sweating, tremor, and a sense of internal agitation or anxiety. Some tumors, however, produce little or no extra hormone and remain asymptomatic.
Common Symptom Pattern: Many people with pheochromocytoma develop sustained hypertension, sometimes with superimposed paroxysms in which blood pressure spikes even higher. Recurrent headaches, heavy or drenching sweating without a clear trigger, and a pounding, fast, or irregular heartbeat are the classic triad. Shakiness or jitteriness during attacks is common and reflects the direct effects of catecholamines on the heart, blood vessels, and nervous system.
Less Common and Atypical Symptoms: Some individuals experience chest or abdominal pain, marked paleness, nausea, vomiting, diarrhea, or constipation during episodes. Others develop unexplained weight loss or a tendency toward an extreme drop in blood pressure when standing abruptly after an episode of intense hypertension. These features are less specific, but when they occur alongside episodic high blood pressure and adrenergic symptoms, they strengthen suspicion for pheochromocytoma.

Attacks can be spontaneous or provoked by identifiable triggers. Intense physical exertion, sudden emotional stress, injury, childbirth, anesthesia, and surgery can all precipitate catecholamine release from the tumor. Certain foods rich in tyramine, such as red wine, aged cheeses, and some cured meats, and some medications, may also provoke or worsen symptoms in susceptible individuals.

Fluctuating Versus Sustained Symptoms: Symptom patterns vary. Some patients live with continuously elevated blood pressure and only subtle additional signs, while others have relatively normal readings between dramatic paroxysmal attacks. These paroxysms can occur multiple times per day, a few times per week, or only intermittently over months, which can make the condition difficult to recognize unless blood pressure and catecholamines are measured at or near the time of symptoms.
Sporadic Cases Without Identified Cause: In the majority of pheochromocytoma cases, no clear external trigger or environmental cause is found, and the tumor appears to arise sporadically. Genetic testing may be negative, and there may be no family history of related conditions. These tumors still require careful evaluation and treatment, but they are not linked to a known inherited syndrome.
Hereditary Syndromes and Genetic Mutations: Approximately one quarter to one third of pheochromocytomas occur as part of inherited syndromes that increase the likelihood of chromaffin cell tumors. These include multiple endocrine neoplasia type 2 (MEN2A and MEN2B), von Hippel–Lindau disease, neurofibromatosis type 1, hereditary paraganglioma syndromes, Carney–Stratakis dyad, and Carney triad. In these settings, pheochromocytoma may accompany other endocrine or nonendocrine tumors. Mutations in at least ten different genes have been implicated in familial pheochromocytoma and paraganglioma, which is why genetic counseling and testing are often recommended, especially in younger patients, those with bilateral or multiple tumors, or those with a suggestive family history.

Diagnosis

How is pheochromocytoma diagnosed?

Pheochromocytoma can be challenging to diagnose because it is rare, its symptoms overlap with far more common conditions, and some tumors produce little hormone and remain asymptomatic. Many are discovered incidentally during imaging performed for unrelated reasons. Clinicians usually begin by asking whether the overall pattern of symptoms, blood pressure changes, and family history suggests catecholamine excess rather than routine hypertension or anxiety, then confirm or exclude the diagnosis with targeted hormone tests and imaging.

Clinical Assessment and Suspicion: A healthcare provider first reviews a detailed medical history, including prior episodes of severe or paroxysmal hypertension, classic “attacks” of headache, palpitations, sweating, weight loss, and any prior cases of pheochromocytoma, paraganglioma, or related hereditary syndromes in the family. A focused examination looks for sustained hypertension, signs of endocrine disease, and consequences of repeated catecholamine surges, such as weight loss or cardiomyopathy. High blood pressure that is difficult to control with standard medications, occurs in sudden spikes, or is accompanied by typical adrenergic attacks raises suspicion for pheochromocytoma and justifies biochemical testing.

Biochemical Screening For Catecholamine Excess: Once clinical suspicion is present, the next step is to document whether catecholamines or their breakdown products are inappropriately elevated. This is done with specialized blood or urine tests that measure catecholamines and their metabolites over time. Because stress, medications, and posture can influence results, clinicians provide specific instructions about preparation, timing, and medications that may need to be adjusted before sampling, and often confirm abnormal results with repeat testing or complementary assays.

Testing

What testing is used to confirm and localize pheochromocytoma?

Twenty-Four Hour Urine Catecholamines and Metabolites: A twenty-four-hour urine test involves collecting all urine over a full day so that the laboratory can measure total catecholamine output and the levels of their breakdown products. Persistently higher than normal amounts of specific catecholamines and metabolites across the collection period support the diagnosis of pheochromocytoma, especially when values are several times above the upper limit of normal and align with the clinical picture.
Plasma Catecholamine and Metabolite Testing: Blood tests can measure catecholamines and their metabolites circulating at a single point in time. When drawn under controlled conditions, markedly elevated levels provide additional evidence of a hormone-producing tumor. These tests are particularly useful when symptoms are frequent, when urine collection is impractical, or when results will guide the urgency and extent of further imaging.
Computed Tomography (CT) of the Adrenal Region: Once biochemical testing indicates catecholamine excess, a CT scan is often used to visualize the adrenal glands and surrounding structures. CT provides detailed cross-sectional images that can reveal a mass in the adrenal medulla, characterize its size and appearance, and identify obvious local extension or suspicious lymph nodes. It also helps detect extra-adrenal masses that might represent paragangliomas when adrenal glands appear normal.
Magnetic Resonance Imaging (MRI) of the Adrenal Region: MRI uses magnetic fields and radio waves to create high-resolution images without ionizing radiation. It is particularly useful in younger patients, in those who cannot receive iodinated contrast, and when CT findings are indeterminate. MRI can help distinguish adrenal medullary tumors from other lesions and map their relationship to nearby vessels and organs, information that is important for surgical planning.
Additional Imaging for Spread and Tumor Characterization: After a pheochromocytoma is identified, additional imaging may be used to assess whether the tumor is confined to the adrenal gland or has spread to nearby nodes or distant sites. Depending on the case, this may include further CT or MRI of the chest, abdomen, and pelvis, or functional imaging that highlights catecholamine-producing tissue. The goal is to determine whether the tumor appears localized, regional, metastatic, or recurrent so that treatment can be tailored appropriately.

Genetic Testing

Is genetic testing for pheochromocytoma recommended?

Because a substantial fraction of pheochromocytomas are associated with inherited syndromes, genetic counseling is often recommended once the diagnosis is confirmed. A genetic specialist reviews personal and family history, explains which hereditary conditions are linked to pheochromocytoma and paraganglioma, and helps select appropriate gene panels. The purpose is to clarify whether the tumor is likely sporadic or part of a broader genetic syndrome that may carry risks for additional tumors in the patient and at-risk relatives.

Genetic testing is particularly important when clinical features suggest a hereditary form of the disease. Situations that commonly prompt testing include a personal or family history of traits associated with inherited pheochromocytoma or paraganglioma syndromes, tumors in both adrenal glands, more than one tumor within a single adrenal gland, diagnosis before about age 40, or catecholamine excess in individuals with other hallmark features of conditions such as multiple endocrine neoplasia type 2, von Hippel–Lindau disease, or neurofibromatosis type 1. When a pathogenic gene change is found, clinicians usually recommend that at-risk family members without current signs or symptoms be offered testing and appropriate surveillance so that tumors can be detected and treated earlier if they arise.

Management and Treatment

How is pheochromocytoma treated?

Treatment for pheochromocytoma centers on safely controlling excess catecholamines and then removing or reducing the tumor whenever feasible. The specific plan depends on factors such as tumor size, whether it appears benign or malignant, whether catecholamine-related symptoms are present, whether the disease is confined to one adrenal gland or has spread, and whether this is a first diagnosis or a recurrence. For localized tumors in medically fit patients, surgery is usually the preferred first-line treatment. When tumors are malignant, metastatic, or not fully removable, additional options such as radiation, chemotherapy, ablation, embolization, and targeted therapies are used to control disease and symptoms.

Preoperative Medical Optimization: Before surgery, most people with a hormonally active pheochromocytoma require medication to stabilize blood pressure and heart rate and to blunt catecholamine surges. Alpha blockers are used to relax blood vessels and maintain blood pressure within a safer range; beta blockers may be added after adequate alpha blockade to control heart rate and palpitations. In some cases, drugs that directly block catecholamine effects are also used. This preoperative preparation lowers the risk of dangerous blood pressure spikes and arrhythmias during anesthesia and tumor manipulation, making surgery safer.

Surgery: Surgery is the primary treatment for pheochromocytoma and, when feasible, offers the best chance of long-term control. In many patients, a procedure called adrenalectomy is performed to remove the adrenal gland containing the tumor, sometimes using minimally invasive techniques. During the operation, the surgeon evaluates the surrounding tissues and regional lymph nodes and removes any visibly involved structures when safe to do so. After surgery, catecholamine levels in blood or urine are checked; normalization of these levels indicates that hormonally active tumor tissue has been successfully removed. If both adrenal glands must be removed, lifelong hormone replacement is required to substitute for cortisol, aldosterone, and other adrenal hormones that the body can no longer produce.

Radiation Therapy: Radiation therapy uses focused energy beams to damage or destroy tumor cells while sparing as much normal tissue as possible. For malignant, unresectable, or recurrent pheochromocytoma, external-beam radiation may be used to treat localized or regional disease, reducing tumor bulk and relieving symptoms. Internal radiation approaches, including 131I MIBG therapy, use a radioactive compound that is preferentially taken up by catecholamine-producing cells; once inside these cells, the radiation they emit helps kill the tumor from within. The choice between external and internal radiation, or a combination of both, depends on tumor location, extent of spread, prior treatments, and overall health.

Chemotherapy: Chemotherapy uses systemic drugs to slow or stop the growth of cancer cells when the pheochromocytoma is malignant or widely metastatic. These medications are typically given intravenously and circulate throughout the body to reach tumor deposits that cannot be removed surgically or targeted with focal therapies alone. Regimens are selected based on tumor behavior, prior treatments, and patient tolerance, with the recognition that chemotherapy can cause side effects that must be monitored and managed alongside its potential benefits.

Ablation Therapy: Ablation therapy offers a minimally invasive way to control selected tumor deposits by destroying them with extreme heat or cold. Radiofrequency ablation uses targeted radio waves delivered through electrodes to heat and destroy cancerous tissue, while cryoablation uses probes that deliver very low temperatures with liquid nitrogen or liquid carbon dioxide to freeze and kill abnormal cells. These techniques are generally reserved for situations in which there are a limited number of accessible lesions, surgery is not possible or would be excessively risky, or local control of specific metastatic sites would meaningfully improve symptoms or quality of life.

Embolization Therapy: Embolization therapy treats pheochromocytoma by deliberately blocking the blood vessels that feed the tumor. Through a catheter placed into the arterial system, tiny particles or other embolic materials are delivered to the artery supplying the adrenal gland or metastatic focus. Reducing blood flow deprives the tumor of oxygen and nutrients, thereby shrinking the lesion and decreasing hormone release. Embolization may be used as a stand-alone palliative measure, as a bridge to surgery, or in combination with other treatments in complex cases.

Targeted Therapy: Targeted therapies are designed to interfere with specific molecular pathways that tumor cells use to grow, divide, or support their blood supply. For metastatic or recurrent pheochromocytoma, agents such as tyrosine kinase inhibitors are being studied and used in selected cases to slow tumor progression. These medications may help control disease when standard options are limited or exhausted, and are typically prescribed and monitored by specialists familiar with their benefits and side-effect profiles. Ongoing research continues to refine which targeted agents are most effective for particular genetic and molecular subtypes of pheochromocytoma.

Shared Decision Making and Long-Term Planning: Management of pheochromocytoma almost always involves a multidisciplinary team that may include endocrinology, surgery, oncology, cardiology, radiology, and genetics. Together with the patient, this team weighs the risks and benefits of each option, sequences therapies in a safe order, and plans long-term follow-up to monitor for recurrence or new tumors. The goal is not only to remove or control the tumor but also to normalize blood pressure, reduce catecholamine-related symptoms, and lower the risk of serious cardiovascular and metabolic complications over time.

Outlook and Prognosis

What is the prognosis (outlook) for pheochromocytoma?

The prognosis for pheochromocytoma is generally favorable when the tumor is recognized and treated. Surgical removal cures hormone excess in most people, and approximately 90 percent of pheochromocytomas can be completely removed with surgery. Once catecholamine levels normalize and blood pressure is controlled, the risk of acute cardiovascular events declines, and many patients return to a normal or near-normal level of daily functioning. Long-term follow-up is still important, particularly for those with hereditary syndromes or malignant tumors, but for the majority of individuals with a solitary, benign adrenal pheochromocytoma, treatment is highly effective and durable.

If a pheochromocytoma is left untreated, excess catecholamines place extreme stress on the heart, blood vessels, and brain. This can lead to serious, potentially life-threatening complications such as cardiomyopathy, myocarditis, uncontrolled bleeding into the brain, acute pulmonary edema, stroke, or myocardial infarction. These complications often arise abruptly during a catecholamine surge triggered by illness, surgery, childbirth, or emotional stress. The contrast between outcomes with and without treatment is substantial, underscoring the critical importance of timely diagnosis, preoperative medical preparation, and definitive tumor management.

Prevention

Can I prevent pheochromocytoma?

There is no reliable way to prevent the development of a pheochromocytoma, because many tumors occur sporadically and others arise from inherited gene changes that cannot be modified. Lifestyle measures that support cardiovascular health do not stop chromaffin cells from becoming neoplastic. What can be influenced is the timing of tumor detection and the rate at which its effects on blood pressure and the cardiovascular system are controlled.

If you are at increased risk because of a known hereditary syndrome or a strong family history, genetic counseling and structured surveillance can help identify tumors at an earlier, more treatable stage. Periodic biochemical screening and imaging, guided by a genetics or endocrinology team, enables detection of small tumors before they cause severe symptoms or complications. For people without known genetic risk, regular blood pressure monitoring and prompt evaluation of unusual patterns such as paroxysmal hypertension, resistant hypertension, or classic attack symptoms remain the main tools for early detection.

Life After Diagnosis

When should I see my healthcare provider?

You should contact a healthcare provider if you have been diagnosed with a pheochromocytoma and notice new or worsening symptoms such as more frequent headaches, episodes of pounding heartbeat, escalating blood pressure readings, chest pain, shortness of breath, or unexplained weight loss. These changes may indicate that hormone output has increased, that blood pressure is not adequately controlled, or that complications are developing, and they warrant reassessment of your treatment plan.

If you have not been diagnosed but experience combinations of high blood pressure, severe or recurrent headaches, heavy sweating without a clear cause, palpitations, or sudden episodes of anxiety with marked blood pressure spikes, it is important to discuss these symptoms with your provider. While pheochromocytoma is rare and most people with hypertension have other causes, these features justify careful evaluation and treatment of blood pressure, and in some cases, testing for catecholamine excess. You should also seek medical advice if a first-degree relative is found to have a pheochromocytoma or a related genetic syndrome such as multiple endocrine neoplasia type 2 or von Hippel–Lindau disease, since this may change your own screening needs.

Patient-Provider Communication

What questions should I ask my doctor?

Living with or newly diagnosed with pheochromocytoma can feel disorienting, especially when you are trying to understand scan reports, hormone levels, and surgical plans all at once. Bringing a focused list of questions to your visits can help you move from feeling overwhelmed to feeling engaged in decisions and clear about next steps.

What do you think caused my pheochromocytoma, and does it appear benign, malignant, or possibly related to a hereditary syndrome on your assessment?

Are my children or other close relatives at increased risk for pheochromocytoma or related tumors because of my diagnosis?

What treatment approach do you recommend for me right now, and why is that option the best fit for my situation?

What short-term and long-term side effects should I expect from the treatments you are recommending, including surgery and any medications?

How should I monitor my blood pressure and symptoms at home between visits to help you see how well treatment is working?

How often will I need follow-up blood tests and imaging in the first few years after treatment?

For how long do you expect to monitor me for recurrence or new tumors, and what will that follow-up schedule look like over time?

Using questions like these as a starting point can clarify your diagnosis, highlight areas of uncertainty, and facilitate sharing decisions with your team. You can add your own questions about work, activity, family planning, or daily life so that the plan you build together addresses not only tumor control but also how you want to live while you are being treated and followed.

The IWBCA provides the information and materials on this site for educational and informational purposes only. The content is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or another qualified healthcare provider regarding any questions you may have about a medical condition, diagnosis, or course of treatment. Do not disregard, delay, or alter medical advice based on information obtained from this site. If you believe you are experiencing a medical emergency, call 911 or your local emergency services immediately.