Adrenal Gland Cancer (Phaeochromocytoma)

Phaeochromocytoma is a rare type of adrenal gland tumor that typically develops in the adrenal medulla — the inner region of the adrenal glands located just above the kidneys. These tumors produce excess amounts of hormones called catecholamines, including adrenaline (epinephrine) and noradrenaline (norepinephrine), which play a key role in regulating heart rate, blood pressure, and the body's stress response.

While phaeochromocytoma is not common — affecting roughly 2 to 8 people per million each year — it can cause severe and unpredictable health crises. Most of these tumors are benign (non-cancerous), but approximately 10% are classified as cancerous phaeochromocytoma, also known as malignant phaeochromocytoma. When cancer cells spread to other parts of the body, the condition is referred to as metastatic phaeochromocytoma.

Phaeochromocytomas can occur at any age, though they most commonly appear in adults between the ages of 20 and 50. A closely related type of tumor — called a paraganglioma — develops outside the adrenal glands but behaves in a similar way and is often discussed alongside phaeochromocytoma.

How Phaeochromocytoma Affects the Adrenal Glands

The adrenal glands are small, triangular organs that sit atop each kidney. Each gland consists of two main parts: the outer cortex and the inner medulla. Phaeochromocytoma arises from chromaffin cells in the adrenal medulla — the same cells responsible for the normal production of adrenaline and noradrenaline.

When a phaeochromocytoma develops, these chromaffin cells grow uncontrollably and begin releasing excessive quantities of stress hormones — sometimes in unpredictable bursts. This overproduction disrupts the body's ability to regulate blood pressure, heart rate, and other essential functions, resulting in the characteristic symptoms of the condition.

The Role of Adrenal Glands and Hormones

In a healthy body, the adrenal glands produce hormones that help manage stress responses, maintain blood pressure, regulate metabolism, and support the immune system. Catecholamines like adrenaline and noradrenaline are released in short bursts during stressful situations, triggering the well-known "fight or flight" response.

In the presence of a phaeochromocytoma, hormone production becomes dysregulated. Rather than releasing these hormones in controlled amounts, the tumor secretes them in large, sudden surges — leading to acute and potentially dangerous physiological changes. This abnormal hormone production is at the heart of most phaeochromocytoma symptoms.

Recognizing Phaeochromocytoma Symptoms

Because phaeochromocytoma causes abnormal surges of catecholamines, its symptoms often mirror those of extreme stress or anxiety. The hallmark features are related to the cardiovascular system, though many other body systems can be affected.

Common Symptoms and Signs

The most frequently reported phaeochromocytoma symptoms include:

• High blood pressure (hypertension) — often severe and difficult to control with standard medications
• Heart palpitations — a rapid, pounding, or irregular heartbeat
• Severe headaches — often described as throbbing or pressure-like
• Profuse sweating — particularly during episodes or attacks
• Pallor or flushing of the skin
• Trembling or shakiness
• Nausea and vomiting
• Anxiety or a sense of impending doom
• Chest or abdominal pain
• Unexplained weight loss

High blood pressure is the most consistent finding across patients with phaeochromocytoma, and in some cases it may be the only sign present. Heart palpitations and headaches, when combined with hypertension and sweating, form a classic symptom triad that should prompt further investigation.

Unpredictable Attacks and Their Progression

One of the defining characteristics of phaeochromocytoma is that symptoms often occur in sudden, unpredictable episodes known as paroxysmal attacks. During these attacks, patients may experience a dramatic spike in blood pressure, intense headaches, heart palpitations, and sweating — all at once. These episodes can last anywhere from a few minutes to over an hour.

Certain triggers are known to provoke these attacks, including physical activity, emotional stress, changes in posture, surgery, or even certain foods and medications. As the tumor grows, episodes may increase in frequency and intensity. In severe cases, a hypertensive crisis — an extreme and abrupt rise in blood pressure — can lead to stroke, heart attack, or organ damage.

When Symptoms May Be Overlooked

Despite its dramatic effects, phaeochromocytoma is frequently misdiagnosed or overlooked. Its symptoms overlap with many other conditions, including anxiety disorders, panic attacks, essential hypertension, and hyperthyroidism. Some patients have only mildly elevated blood pressure without the classic episodic symptoms, making diagnosis even more challenging.

In approximately 10 to 15% of cases, phaeochromocytomas are discovered incidentally during imaging done for unrelated reasons. This reinforces the importance of thorough clinical evaluation, especially in patients with persistent, difficult-to-treat hypertension or unexplained cardiovascular symptoms.

Understanding the Causes of Phaeochromocytoma

The exact cause of phaeochromocytoma is not fully understood in all cases, but both genetic and non-genetic factors appear to play a role. Research suggests that up to 40% of phaeochromocytomas are associated with hereditary genetic mutations, making genetic testing an important part of evaluation for many patients.

Known genetic conditions linked to phaeochromocytoma include:

• Multiple Endocrine Neoplasia type 2 (MEN2) — a hereditary syndrome affecting the thyroid, parathyroid, and adrenal glands
• Von Hippel-Lindau (VHL) disease — a condition that causes tumors to grow in multiple organs
• Neurofibromatosis type 1 (NF1) — a genetic disorder affecting the nervous system
• Hereditary paraganglioma-phaeochromocytoma syndromes — caused by mutations in succinate dehydrogenase (SDH) genes

Genetic testing is now recommended for most patients diagnosed with phaeochromocytoma, regardless of age or family history, as identifying a hereditary mutation has important implications for the patient and their relatives. Non-hereditary cases are thought to result from sporadic mutations that occur without a clear inherited cause.

Diagnosing Phaeochromocytoma

Phaeochromocytoma diagnosis typically involves a combination of biochemical tests, imaging studies, and in some cases, genetic testing. Because symptoms can mimic other conditions, a structured diagnostic approach is essential.

The first step in diagnosing phaeochromocytoma is usually a biochemical test to detect elevated levels of catecholamines or their breakdown products. The most sensitive tests include:

• 24-hour urine catecholamines and metanephrines — measures hormone levels excreted in urine over a full day
• Plasma free metanephrines — a blood test measuring catecholamine metabolites, considered highly accurate for phaeochromocytoma diagnosis

If biochemical results are elevated, imaging is used to locate the tumor. Common imaging techniques include:

• CT (computed tomography) scan — the first-line imaging modality for identifying adrenal tumors
• MRI (magnetic resonance imaging) — particularly useful for patients who cannot receive CT contrast agents
• MIBG scintigraphy (metaiodobenzylguanidine scan) — a nuclear medicine scan that can detect phaeochromocytoma tissue throughout the body, especially useful for metastatic phaeochromocytomas
• PET scan — increasingly used for identifying metastatic or recurrent disease

Genetic testing is recommended following diagnosis to identify any hereditary mutations that could affect treatment planning and family screening.

Phaeochromocytoma Treatment Options

The primary treatment for phaeochromocytoma is surgical removal of the tumor. However, careful preparation is required before phaeochromocytoma surgery to prevent dangerous blood pressure fluctuations during the procedure.

Pre-operative management typically involves:

• Alpha-blockers — medications that relax blood vessels and help control blood pressure for 1 to 3 weeks before surgery
• Beta-blockers — sometimes added after alpha-blockade to control heart rate, but never prescribed alone first
• Adequate hydration and dietary salt intake — to prevent a severe drop in blood pressure after tumor removal

Phaeochromocytoma surgery is most commonly performed laparoscopically (minimally invasive), which offers faster recovery, less pain, and shorter hospital stays compared to open surgery. For larger tumors or those suspected to be malignant, open surgery may be necessary. The surgery aims to remove the entire tumor while preserving as much of the adrenal gland as possible.

For patients with metastatic phaeochromocytomas, where the cancer has spread beyond the adrenal gland, treatment becomes more complex and may include:

• MIBG therapy (high-dose radiolabelled MIBG) — a targeted radiotherapy that delivers radiation directly to phaeochromocytoma cells
• Chemotherapy — used in some cases of rapidly progressive metastatic disease
• Peptide receptor radionuclide therapy (PRRT) — a newer targeted radiation therapy
• Tyrosine kinase inhibitors and other targeted therapies — under investigation in clinical trials

Regular follow-up is essential after phaeochromocytoma treatment, as there is a risk of recurrence — even years after apparently successful surgery.

Potential Complications and Long-Term Outlook

If left untreated or undiagnosed, phaeochromocytoma can lead to serious and life-threatening complications. Persistent high blood pressure can damage the heart, kidneys, blood vessels, and brain over time. Hypertensive crises — sudden, extreme spikes in blood pressure — can trigger strokes, heart attacks, or multiple organ failure.

Surgical and perioperative risks are also significant. Blood pressure instability during phaeochromocytoma surgery can be dangerous, which is why pre-operative preparation with alpha-blockers is so critical.

For patients with benign, localised phaeochromocytoma that is successfully removed, the long-term outlook is generally favourable. Blood pressure typically normalises after surgery, and quality of life improves considerably. However, patients require lifelong monitoring because:

• The risk of recurrence is approximately 10 to 15% after 10 years
• New tumors can develop, particularly in those with hereditary mutations
• Annual biochemical testing and periodic imaging are recommended for life

For metastatic phaeochromocytoma, the prognosis is more variable and depends on the extent of disease, the rate of progression, and response to treatment. The five-year survival rate for metastatic cases is approximately 40 to 60%, though advances in targeted therapy are improving outcomes.

Living with Phaeochromocytoma

A phaeochromocytoma diagnosis can be overwhelming, but with appropriate medical care, most patients go on to live full and active lives — especially after successful surgery. Understanding the condition and working closely with a specialist team is key to managing it effectively.

Patients are typically advised to:

• Avoid known triggers that can provoke hormonal surges, including intense physical exertion, stress, and certain medications
• Monitor blood pressure regularly at home and report any unusual symptoms promptly
• Attend all follow-up appointments, including annual biochemical blood and urine tests
• Undergo genetic counselling if a hereditary mutation is identified, and encourage relatives to be tested
• Seek psychological support if anxiety, stress, or emotional difficulties arise from living with the condition

Patients with hereditary conditions linked to phaeochromocytoma — such as MEN2 or VHL disease — will need additional specialist surveillance for other associated tumors and conditions. With growing awareness, improved diagnostic tools, and advancing treatments — including more precise surgical techniques and innovative therapies for metastatic phaeochromocytomas — the outlook for patients continues to improve.

Early diagnosis and specialist management remain the most important factors in achieving the best possible outcomes. At Medical Park Hospitals in Turkey a multidisciplinary team including endocrinologists, general surgeons, oncologists, and geneticists ensures that all aspects of care are coordinated.