Pheochromocytoma - A Rare Adrenal Tumor

What Is Pheochromocytoma?

Pheochromocytoma is a neuroendocrine tumor of the chromaffin cells. These cells are located in the adrenal glands above the kidneys and produce hormones. The adrenal medulla, the inner layer of the adrenal gland, is where 80 to 85% of most pheochromocytomas develop. 15 % to 20 % of pheochromocytomas, also known as paragangliomas or extra-adrenal pheochromocytomas, develop outside of this region. Most pheochromocytomas are benign, meaning they do not spread to other parts of the body and are not cancerous. Only 10 % of pheochromocytomas disseminate to different parts of the body.

How Does Pheochromocytoma Develop?

The cause of pheochromocytoma is unknown, but about 20 mutated genes contribute to developing pheochromocytoma and paraganglioma. Mutations may cause pheochromocytoma and paragangliomas in RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, MDH2, IDH1, PHD1/PHD2, HIF2A/EPAS1/2, TMEM127, MAX, HRAS, MAML3, and CSDE1.

The following genetic disorders elevate the risk of developing pheochromocytoma are:

• Types A and B of multiple endocrine neoplasia syndromes (MEN2A and MEN2B) (a disorder of the endocrine gland).

• Von Hippel-Lindau syndrome (VHL) (a rare, inherited disorder affecting multiple organs).

• Type 1 neurofibromatosis (NF1) (a disorder of the skin color).

• Carney-Stratakis dyad syndrome (gastrointestinal disorder).

• Hereditary paraganglioma syndrome (tumor of the nerves).

How Frequently Does Pheochromocytoma Occur?

Adults between 30 and 50 are most frequently affected by pheochromocytoma. According to one estimate, just eight persons out of every million people have pheochromocytoma.

Is Pheochromocytoma Hereditary?

Pheochromocytoma may occasionally run in families. Pheochromocytoma instances that are 25 to 35 percent hereditary may occur. Some inherited cases, like multiple endocrine neoplasia types 2a and 2b, Von Hippel-Lindau syndrome, and neurofibromatosis, may be linked to a genetic disorder.

What Are the Clinical Signs and Symptoms of Pheochromocytoma?

The various signs and symptoms are as follows:

1. Headache.

2. Sweating.

3. Palpitations.

4. Stress and anxiety.

5. Flushing.

6. Chest pain.

7. Warmth or sensitivity to heat.

8. Dizziness.

9. Raynaud's syndrome (numbness in the small arteries of the legs and hands).

10. Cardiomyopathy (enlargement of the heart muscles).

11. Gain weight.

12. Excessive urination.

13. Excessive thirst.

14. Nausea and vomit.

15. Pale appearance.

16. Tremor.

17. Constipation.

18. Diarrhea.

What Are Malignant Pheochromocytomas?

Malignant pheochromocytomas exhibit signs of distant metastases and tumor infiltration. People commonly develop metastases in the lung and the liver. The diagnosis of pheochromocytoma rules out in every case of chronic paroxysmal hypertension despite antihypertensive medication, particularly during therapy with b-blockers. Pheochromocytoma may be suggested by the sudden onset of hypertension while taking tricyclic antidepressants with a-blockers.

What Is the Differential Diagnosis of Malignant Pheochromocytoma?

The differential diagnosis includes other types of secondary hypertension, including renal artery stenosis, hypercortisolism, and hyperaldosteronism. Additionally, hyperthyroidism, panic episodes, hypoglycemia, and signs of alcohol withdrawal can all mimic pheochromocytoma symptoms.

What Are the Methods for Diagnosing Pheochromocytoma?

Pheochromocytoma symptoms can vary from person to person. The frequency of symptoms might range from several times per day to a few times per month. Paroxysmal attacks, or severe symptoms, may occur in some individuals. These signs may include sweating, irregular heartbeat, headaches, and high blood pressure.

The following tests establish the diagnosis:

Urine and Blood Tests- To examine the hormone levels.

Testing for Plasma Metanephrine- A person with predisposing genetic syndromes or a family or personal history of pheochromocytoma is subjected to a plasma metanephrine test. It has a 96 % sensitivity rate and an 85 % specificity rate.

The following are some diagnostic tests for pheochromocytoma:

Catecholamine and Metanephrine Detection-

The urine testing is done over 24 hours. It has an 87.5 % sensitivity and a 99.7 % specificity rate.

A person at reduced risk should undergo 24-hour urine collection for catecholamines and metanephrines.

Imaging-

Imaging tests like computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) will help determine the location and size of the tumor. Additionally, they will also aid in locating if cancer has migrated to other bodily regions. They are carried out once biochemical tests have established the pheochromocytoma's diagnosis.

Abdominal Computed Tomography(CT) scan-

Abdominal CT scanning has an accuracy of 85-95 % for identifying adrenal masses with a spatial resolution of 1 cm or more.

Magnetic Resonance Imaging (MRI)-

It helps to detect adrenal pheochromocytomas, making it preferred over CT screening in children and pregnant or lactating women.

Scintigraphy-

They are used only in cases of biochemical confirmation when MRI or CT scans failed to detect malignancy.

Positron Emission Tomography (PET) Imaging-

A potential method for locating and detecting pheochromocytomas

In people with confirmed pheochromocytoma, additional research to rule out a family condition, including the following:

1. Blood calcium level.

2. Parathyroid hormone levels rule out primary hyperparathyroidism that occurs in MEN 2A.

What Are the Treatment Options for Pheochromocytoma?

Pheochromocytoma treatment may involve various medical professionals, including specialists in cancer diagnosis and treatment and hormone issues. The following are treatment alternatives to go over with:

1. Alpha- and Beta-Blockers- They are medications for high blood pressure and may be prescribed.

2. Surgery- All the feasible tumors are removed during surgery. The entire adrenal gland may need to be released in some situations.

3. Radiation Therapy and Chemotherapy- Radiation therapy and chemotherapy are employed as therapeutic options when pheochromocytoma has migrated to other bodily regions.

What Is the Treatment for Malignant Pheochromocytoma?

Surgery, Chemotherapy, and Radiotherapy-

• They are the primary treatment components for malignant metastatic pheochromocytoma, which aims to reduce tumor size and stop tumor endocrine activity.

• Surgery is rarely a curative treatment since, after surgery, tumor tissue typically still exists.

131I-MIBG (Iodine-131 Metaiodobenzylguanidine) Treatment-

• 131I-MIBG can be employed as a treatment alternative when surgery is not an option.

• 131I-MIBG therapy is well tolerated and can be applied repeatedly. It is up to each person to decide on their dose, therapy intervals, and the number of therapy cycles.

• There are currently no established recommendations for 131I-MIBG treatment.

• Therapy with 131I-MIBG increases survival time and relieves symptoms.

Octreotide Treatment-

• This treatment is employed if 131I-MIBG absorption is poor because some pheochromocytomas express type 2 and 3 somatostatin receptors.

How Likely Is It That Someone With Pheochromocytoma Will Survive?

Prognosis assesses how an illness will affect the body over the long run. The prognosis depends on a variety of variables, including:

1. The location of the tumor.

2. The amount of tumor removed during surgery. The extent to which cancer has spread to other body regions.

The five-year survival percentage for people with a small pheochromocytoma without metastasis is approximately 95 %. Between 34 % and 60 % of people with recurrent or distant pheochromocytomas survive five years after diagnosis.

Conclusion

It is necessary to understand the value of a high percentage of clinical suspicion for pheochromocytoma for a prompt and accurate diagnosis. It is crucial to frame the disease's clinical symptoms in the specific patient and treat them accordingly. However, the condition of the patient can be improved if the disease is diagnosed beforehand and prompt treatments are administered.