Adrenal Gland Cancer (Pheochromocytoma)

Adrenal gland cancer (pheochromocytoma) is a rare tumor originating from the center of the glands located just above the kidneys, which uncontrollably produces adrenaline and noradrenaline and releases them into the bloodstream. The treatment of pheochromocytoma is based on completely removing the tumorous tissue from the body through specialized urological surgical interventions following a special medical preparation process that dilates the blood vessels and lowers blood pressure to safe limits. These masses, which pose a life-threatening risk due to excessive stress hormone release and present with sudden high blood pressure attacks, severe palpitations, and sweating, can now mostly be permanently and safely removed using minimally invasive (laparoscopic) or robotic surgical techniques.

What Are the Main Differences Between Adrenal Gland Cancer (Pheochromocytoma) and Paraganglioma?

Our body has a sympathetic nervous system network that is activated in times of danger. The hormone-producing cells in the inner part of the adrenal gland are actually part of this enormous network. If this hormone-producing mass develops right in the heart of the adrenal gland, in its own anatomical location, it is called pheochromocytoma. However, there are also similar masses arising from nerve ganglia outside the adrenal gland in other regions of the nervous system. These are called paragangliomas. Although these two formations look very similar under a microscope, they are completely distinguished from one another in terms of their locations in the body.

In the vast majority of patients, the mass is located directly inside the adrenal gland. In the remaining small group, it may occur in other nerve ganglia in the neck, chest cavity, or deep within the abdominal cavity. While some tumors developing outside the adrenal gland remain completely silent and produce no hormones, those inside the adrenal gland function like highly active hormone factories. By continuously pumping powerful stress hormones into the blood, they keep the body in a constant state of panic, stress, and high blood pressure.

The main hormones produced by the tumors and released into the blood are as follows:

• Adrenaline
• Noradrenaline
• Dopamine

Excessively high levels of these hormones in the blood cause the patient to constantly experience palpitations, sweating, and unexplained headaches.

Does the Small Size of Adrenal Gland Cancer (Pheochromocytoma) Mean That the Danger Is Lower?

As a general perception in medical conditions, it is thought that the smaller a mass in the body is, the lower the danger it creates. However, in this particular type of tumor, as a surprising twist of human physiology, the situation may work in exactly the opposite way. An increase in tumor size does not always progress in direct proportion to the severity of the crises experienced by the patient. In fact, small tumors may often expose the patient to much greater life-threatening risks.

Large masses have a highly developed vascular and tissue structure within themselves. Instead of releasing the excessive amount of hormones they produce directly into the blood, these masses have the ability to store them internally first and break down part of them to render them ineffective. Therefore, a tumor that has reached an enormous size may leak much less active hormone into the bloodstream than expected. However, when the mass is small, this internal storage and hormone breakdown mechanism has not yet developed. Small tumors release the extremely powerful stress hormones they produce directly into the bloodstream without encountering any barrier or passing through any filter. This causes the patient to experience sudden, very severe, and difficult-to-control blood pressure attacks.

The life-threatening risks that may arise due to hormones pumped directly into the blood by small tumors are as follows:

• Heart attack
• Cardiac rhythm disturbances
• Brain hemorrhage
• Kidney failure

For this reason, seeing on ultrasound or tomography that the mass is still very small should not create the misconception that the danger has decreased, and treatment planning should continue with the same seriousness.

Is There a Role of Genetic Predisposition or Family History in the Development of Adrenal Gland Cancer (Pheochromocytoma)?

In previous years, this condition was thought to arise mostly by complete chance without any obvious underlying cause. However, the tremendous progress made by modern medicine in combination with genetic science has revealed that this is not the case at all. It is now known that approximately one-quarter of these cases occur directly as a result of a genetic disorder inherited from the family. This is an extremely high rate and demonstrates how vital the family’s medical history is in diagnosing the disease.

Suspicion of genetic transmission is especially strong in those who encounter this tumor at a young age, those who develop tumors in both adrenal glands, or those whose family members have similar diseases. Identifying genetic predisposition provides a critical opportunity for the early detection not only of this tumor but also of other dangers that may be hidden in the body. For example, in individuals carrying a specific gene mutation, the risk of dangerous cellular changes beginning within the kidney tissue itself at the same time as this tumor is quite high. Therefore, during the urological evaluation, not only the adrenal gland but also the kidney itself is examined with millimetric precision.

The main genetic syndromes and mutations known to predispose to the disease are as follows:

• MEN-2 syndrome
• Von Hippel-Lindau syndrome
• Neurofibromatosis Type 1
• Fumarate hydratase gene mutations

For this reason, when a familial connection is detected, including the patient’s first-degree relatives in the genetic counseling process is an indispensable medical necessity for early diagnosis.

Which Tests Are Performed to Diagnose Suspected Adrenal Gland Cancer (Pheochromocytoma)?

When this particular tumor is suspected in a patient, there is a much more important step that must be taken before directly performing imaging studies to search for the tumor: finding the chemical fingerprint left by the tumor in the body. Since these tumors constantly produce hormones, the broken-down remnants of these hormones accumulate in body fluids. The first and most reliable method of diagnosis is to analyze these hormone remnants in detail.

The most commonly used method for this purpose is an analysis performed on urine collected over 24 hours. The patient is asked to collect their urine throughout one day under special conditions in a dark and cool environment. The urine is kept acidic with protective substances added to it to prevent the hormone remnants from breaking down. In this way, the amount of stress hormones filtered through the kidneys can be measured clearly. If there is a family history of the disease or if a more definitive result is desired quickly, hormone measurements may also be performed directly on blood samples instead of a urine test. Blood tests provide extremely sensitive results in showing the tumor’s current activity.

However, there are many external factors that impair the reliability of these tests and may completely mislead the results. Before laboratory measurements, many substances consumed by the patient in daily life may cause incorrect test results.

The substances that may directly affect test results and should be discontinued beforehand are as follows:

• Antidepressant medications
• Decongestant cold medications
• Certain blood pressure medications
• Painkillers
• Caffeinated beverages
• Alcohol

The use of these substances may cause the tests to appear positive as though the person were ill even if they are completely healthy, or conversely, to appear normal despite the presence of a mass. Therefore, the preparation process before the tests is at least as important as the test itself.

How Is Adrenal Gland Cancer (Pheochromocytoma) Confirmed by Blood and Urine Tests Located in the Body?

After laboratory tests definitively prove that excessive amounts of stress hormones are circulating in the body, the physician’s main task is to map the production center of these hormones, in other words, to determine where the tumor is hidden. For this purpose, the most powerful tools available to the medical world are advanced technological imaging systems.

In the first step, computed tomography or magnetic resonance imaging (MRI) is generally used. When a mass is detected in the adrenal gland, it is necessary to determine whether it is a simple, harmless fatty growth called an adenoma or a dangerous hormone factory. On tomography, the rate at which the special contrast agent given to the patient penetrates the mass and is then washed out is examined. These tumors reveal themselves easily through their ability to retain the contrast material. MRI is the first preferred method especially in pregnant women because it does not emit radiation, and these tumors appear on the MRI screen with a very bright color tone compared with other tissues, almost like a glowing light bulb.

However, sometimes the mass may be hidden not in the adrenal gland but in nerve tissues in very different parts of the body. Sometimes it may also be too small to be seen with the naked eye. In such cases, much more advanced tracking methods offered by nuclear medicine are used. By taking advantage of the tumor cells’ eagerness to absorb hormones, liquids labeled with special radioactive substances are given to the patient, and the tumor is expected to absorb these liquids and light up.

The main imaging methods used to confirm the diagnosis and determine the location are as follows:

• Computed tomography
• Magnetic resonance imaging
• MIBG scintigraphy
• PET-CT scans

The millimetric maps provided by these devices allow the surgeon performing the operation to create the surgical plan flawlessly.

Why Is Very Special Medication Treatment Needed Before Adrenal Gland Cancer (Pheochromocytoma) Surgery?

The definitive solution to the disease is the complete surgical removal of the tumor from the body. However, taking the patient to the operating room in haste immediately after diagnosis is one of the greatest, even fatal, medical mistakes that can be made. In these patients, a very strict and special preoperative medication preparation period, sometimes lasting for weeks, is essential. If surgery is performed directly without this preparation, the rate of life-threatening danger on the operating table rises to unacceptably high levels.

The main source of the problem is that all the blood vessels in the body have been severely constricted for a very long time due to the excessive adrenaline released into the blood by the mass. When the vessels constrict, the area through which blood flows narrows and blood pressure reaches dangerous levels. Before surgery, it is essential to widen this constricted vascular bed, lower blood pressure to safe limits, and stabilize the rhythm of the heart. For this purpose, a medication sequence governed by very strict medical rules is followed.

It is a mandatory rule that treatment must always begin first with medications that dilate the blood vessels. It is strictly prohibited to use medications that slow the heart before the vessels have been completely relaxed and widened. Otherwise, if the heart slows while the vessels remain constricted, it has difficulty pumping blood and sudden heart failure or severe crises may occur.

The medication groups used successively during the preparation process are as follows:

• Alpha-blockers
• Beta-blockers
• Calcium channel blockers

Thanks to these medications, the body’s vascular system is relaxed and widened, and the patient’s body is strongly protected against possible hormone fluctuations during surgery.

Why Are Patients Given Intensive Fluid Supplementation Before Adrenal Gland Cancer (Pheochromocytoma) Surgery?

When medication treatment that widens the blood vessels is started before surgery, a very interesting physical change occurs in the patient’s body. Due to months or even years of exposure to high levels of stress hormones, the inside of the patient’s blood vessels has actually become severely depleted of fluid. Although it is not apparent from the outside, the total blood and fluid volume within the constricted vascular bed is much lower than that of a normal person. The patient’s vascular system resembles a narrow riverbed from which the water has receded.

When these vessels are suddenly widened with medications, the small amount of blood present is not sufficient to fill the expanded vessels. In this new situation, where there is little water and a wide bed, the patient’s blood pressure begins to fall suddenly and very severely. Dizziness and darkening of vision may occur, especially when the patient stands up. More importantly, in the first seconds when the tumor is removed from the body on the operating table, the vessels relax completely because the hormone entering the blood is suddenly cut off. If the vessels are not filled with fluid, the patient may go into shock.

There is only one way to prevent this and make the surgery safe. The patient’s intravascular volume must be artificially replenished in the days before surgery.

For this purpose, the supportive steps applied before surgery to patients admitted to the hospital are as follows:

• Continuous intravenous fluid administration
• Implementation of a diet very rich in salt
• Close monitoring of blood pressure values
• Monitoring of pulse and heart rhythm

In this way, the expanded vascular system is filled with a large amount of fluid, sudden drops in blood pressure during surgery are prevented, and surgical safety is maximized.

Which Urological Surgical Methods Are Used for the Definitive Treatment of Adrenal Gland Cancer (Pheochromocytoma)?

Complete removal of the disease from the body and restoration of the patient’s health are only possible through surgical intervention. Patients whose bodies have been prepared for surgery with medication treatment and fluid supplementation undergo surgery using various surgical methods offered by modern urology. While in the past the only option was a difficult operation performed through a large incision in the abdominal area, today, with the development of medical technology, much more comfortable minimally invasive methods have become standard. The method to be selected is determined with great care according to the size of the mass, the patient’s body structure, and the location of the disease.

Minimally invasive methods (laparoscopy) include procedures performed by inserting a camera and thin instruments through several small openings made in the abdominal area. Thanks to these methods, no large scar forms on the skin, the pain felt after the operation is minimal, and the patient recovers quickly enough to return home within a few days. Depending on the location of the mass, the surgeon may perform the procedure by advancing through the patient’s anterior abdominal wall or by entering through the patient’s back and reaching the adrenal gland directly without touching the internal organs. If the tumor has reached an enormous size or is tightly attached to surrounding organs, classical open surgery may also be used instead of minimally invasive operations.

The main urological surgical methods currently preferred to remove the tumor from the body are as follows:

• Classical open surgery
• Laparoscopic transperitoneal surgery
• Laparoscopic retroperitoneal surgery
• Robot-assisted laparoscopic surgery

The surgeon evaluates the patient’s general condition and the characteristics of the mass and determines the safest option with great care.

What Advantages Does Robotic Surgery Provide Over Minimally Invasive Operations in the Treatment of Adrenal Gland Cancer (Pheochromocytoma)?

Robotic surgical systems represent the highest point reached by minimally invasive surgical techniques in the medical world. Although laparoscopic operations are revolutionary compared with open surgery, the image seen by the surgeon on the screen is two-dimensional, and the range of motion of the instruments used is not as free as the movements of a human wrist. However, when surgical robots become involved, the rules change completely. Especially if the mass is large, located in an anatomically difficult region, or the patient is severely overweight, robotic systems provide urology specialists with unique capabilities.

The camera of the robotic system projects the surgical area onto the screen at ten times the size the human eye can see, with extreme clarity and in true three-dimensional (3D) form. The surgeon sits at a special console beside the patient and works within this enormous image. The robot’s arms have special joints that never tremble and can rotate through far greater angles than the human wrist. Since the adrenal gland is located deep within the body and very close to large vessels, this precision is of vital importance. With millimetric movements, the surgeon can separate the tumor from the surrounding tissues without damaging the vessels.

In addition, in hereditary diseases, tumors may be present in both adrenal glands. To avoid condemning the patient to lifelong external hormone medication, it may be necessary to preserve healthy tissue and remove only the tumorous tissue. The micro-level precision of robotic surgery allows these organ-preserving operations to be performed much more safely.

The main advantages offered by robotic surgery to the patient and surgeon are as follows:

• True three-dimensional and magnified imaging
• Tremor-free arms with high mobility
• Superior safety around large vessels
• Very rapid postoperative recovery
• Ability to preserve healthy tissue

What Is the No-Touch Principle Applied During Adrenal Gland Cancer (Pheochromocytoma) Surgery and Why Is It Life-Saving?

Pheochromocytoma surgery has a unique and extremely dangerous characteristic that distinguishes it from all other surgical procedures in the world. This tumor is like a fragile balloon filled to the brim with concentrated adrenaline or a ticking time bomb. Touching the tumor during surgery, applying pressure with instruments, or moving the mass from its position causes these hormones inside it to be released directly into the bloodstream within seconds. This intense wave of stress hormones suddenly entering the blood may instantly raise the patient’s blood pressure to fatal levels.

To prevent this disastrous scenario, the urology specialist performing the operation applies a very special and demanding surgical discipline called “No-Touch.” According to this rule, while cutting the fat and attachments around the tumor, the surgeon never touches or applies pressure to the tumor itself. The most crucial point of the procedure is finding the vessel that carries the blood inside the tumor into the body’s main circulation. Before moving the tumor from its position, the surgeon skillfully finds this main vessel, closes it with clips, and cuts it. The moment that vessel is ligated, the tumor’s entire biological connection with the body and its hormone transmission line are severed. Even if the mass is touched afterward, the hormones can no longer spread through the body.

The main objectives of this no-touch principle, which lies at the center of the entire surgical process, are as follows:

• Preventing a hormone storm
• Preventing sudden blood pressure surges
• Preventing cardiac rhythm disturbances
• Eliminating the risk of brain hemorrhage and heart attack

This skill-intensive step, known as early vascular control, is the most critical threshold for the successful completion of the operation.

How Is the Treatment Process Planned If Adrenal Gland Cancer (Pheochromocytoma) Is Detected During Pregnancy?

Encountering this tumor during pregnancy is an extremely rare but highly special situation that carries major risks for both the mother and the baby. High blood pressure and hormonal imbalance circulating in the body make the pregnancy process more difficult. When such a diagnosis is made, the treatment strategy to be applied by physicians differs completely according to the month of pregnancy.

If the tumor is detected in the early stages of pregnancy, in other words during the first months, surgery is relatively safer because the developing baby does not yet occupy much space in the womb. After the mother’s blood pressure has been secured with medications, the mass is removed using minimally invasive surgical methods, allowing the remainder of the pregnancy to proceed more safely. However, if the tumor is noticed in the months close to delivery, during the later stages of pregnancy, the surgical area becomes very narrow because of the enlarged uterus. At this stage, surgery is postponed until delivery, and the mother is placed under very close medical follow-up while her blood pressure is tightly controlled with medications.

When the time of delivery arrives, normal vaginal delivery is strictly prohibited. This is because pushing and contractions during normal delivery may physically compress the tumor and cause a tremendous hormone wave to be released into the expectant mother’s blood. To prevent this situation, a cesarean delivery is planned. While the delivery is taking place, the urology and surgical teams simultaneously become involved at the same operating table and also remove the mass.

The main factors determining the roadmap in this complex treatment process are as follows:

• The month of pregnancy
• The baby’s physiological development status
• The stability of the mother’s blood pressure
• The area occupied by the tumor and its size

What Happens During the Intensive Care Process After Adrenal Gland Cancer (Pheochromocytoma) Surgery?

When the surgical procedure is successfully completed and the tumor is removed from the body, a very severe hormonal earthquake occurs in the patient’s body. The powerful source of hormones that had constricted the vessels and raised blood pressure for years or months has suddenly disappeared. Moreover, the effects of the vessel-dilating medications administered before surgery are still continuing in the body. When all these changes overlap, the body cannot immediately adapt to the new situation.

When the absence of the hormone and the continuing effect of the medications combine, sudden and profound drops in the patient’s blood pressure are inevitable. This may strain the cardiovascular system. At the same time, the pancreas, which had been suppressed while the tumor was present, begins releasing insulin uncontrollably into the blood after the tumor is removed, causing blood sugar to suddenly fall to very low levels. Because of all these vital fluctuations, patients are not sent to their normal rooms immediately after leaving the operating room. They are kept under close observation in a special intensive care unit until their body systems find a new balance. Here, patients are continuously given fluids, intravenous solutions, and sugar supplementation when necessary. Most patients pass through this period without problems within a few days and are transferred to a normal room. It is even observed that some individuals who had diabetes before surgery no longer require insulin at all after the operation.

The main values monitored continuously and with great care in the intensive care unit immediately after surgery are as follows:

• Blood pressure
• Heart rhythm
• Blood sugar
• Fluid balance

How Should Long-Term Follow-Up Be After Adrenal Gland Cancer (Pheochromocytoma) Treatment and Can the Disease Recur?

When the time comes for discharge from the hospital after surgery or during the immediately following week, blood and urine tests are repeated to confirm that the dangerous hormones in the body have been completely reduced to zero. The normalization of the results is the clearest indicator that the surgery has achieved its goal. However, this type of tumor may have a highly insidious nature. Even though the tumor is completely removed and the disease is permanently treated in the vast majority of patients, there is a possibility that the disease may reappear years later in the same region or in a completely different part of the body in approximately one out of every ten patients.

In pathological examinations, it is not always possible to clearly distinguish with certainty whether these tumors are benign or malignant. The only definitive and unchanging proof that they are malignant is the spread of the tumor years later to other organs such as the lungs, liver, or bones. The most striking aspect is that these recurrences or metastases may occur even ten or twenty years after the first successful operation. Therefore, the relationship between the treated patient and the physician should never be completely severed, and the follow-up process should continue almost for a lifetime.

If the disease recurs in later years, surgically removing all accessible masses from the body remains the most valid and successful treatment method.

The procedures that should be performed regularly during long-term follow-up against the risk of disease recurrence are as follows:

• Urine tests at certain intervals
• Blood tests
• Blood pressure measurements
• Physical examination
• Radiological imaging

Frequently Asked Questions