Pheochromocytoma : Causes, Symptoms, Diagnosis, Treatment And Prognosis

A Pheochromocytoma is a rare tumor that develops in the center of one or both of your adrenal glands. The hormones that trigger the "fight or flight" response are produced and released by a specific type of cell called a chromaffin cell, which makes up the tumor.

Pheochromocytoma often affects just one adrenal gland, although it can also affect both. Multiple tumors can occasionally exist in a single adrenal gland.

The vast majority of pheochromocytomas are benign (not malignant). Pheochromocytomas may be malignant (cancerous) in 10% to 15% of cases. If a pheochromocytoma is malignant, there is no set staging system for it. Instead, this is how it's described:

• Localized pheochromocytoma: Only one or both adrenal glands are affected by the tumor.
• Regional pheochromocytoma: The cancer has progressed to the tissues close to your adrenal glands, such as lymph nodes.
• Pheochromocytoma that has metastasized means the cancer has spread to other organs such the liver, lungs, bone, or distant lymph nodes.
• Recurrent pheochromocytoma: Following treatment, the cancer has returned. It can reappear there or in another area of your body.

When the tumor releases too much adrenaline (epinephrine) or noradrenaline (norepinephrine) into your blood, it causes signs and symptoms of pheochromocytoma. Some pheochromocytoma tumors, however, don't produce any more noradrenaline or adrenaline and don't manifest any symptoms (are asymptomatic).

Pheochromocytomas are also known as 10% tumor: 

• 10% malignant
• 10% Bilateral
• 10% seen in pediatric population
• 10% familial
• 10% extra-adrenal

Read this blog further to get a quick overview of this important topic for medicine and ace your NEET PG exam preparation.

Causes of Pheochromocytoma

• Can be sporadic/familial.
• Can be syndromic or non-syndromic.
• The syndromes that are associated with pheochromocytomas are the following (Mnemonics: “MVVS”):
  • MEN 2A / 2B
  • VHL syndrome 
  • Von-Recklinghausen syndrome (Also known as NF – 1): Most commonly associated with pheochromocytomas. 
  • Sturge-Weber syndrome 
• Non-syndromic familial association of pheochromocytomas are the following:
  • Associated with succinyl dehydrogenase D and B mutation.

Symptoms Of Pheochromocytoma

• Pheochromocytoma is characterized by a classical triad. The components of a classical triad are as follows (Mnemonic: “PHD”):
  • Palpitations
  • Headache (Pounding headache)
  • Diaphoresis 
• Other manifestations include:
  • Chest pain
  • Anxiety
• The symptoms are easy to understand. There will be increased secretion of catecholamines (which leads to increased gluconeogenesis). This causes:
  • Carbohydrate intolerance
  • Weight loss – Due to increased energy expenditure. 
  • Ileus – Due to sympathetic overactivity.
  • Cardiac manifestations:
    • Sinus tachycardia
    • Supraventricular arrhythmia
    • Ventricular premature contractions

Diagnosis Of Pheochromocytoma

• Since the catecholamines and VMA are excreted into the urine, the most sensitive screening test to detect pheochromocytoma is 24 Hours Urinary catecholamines and VMA level. 
• Best test for diagnosis is Plasma free Metanephrine. Neuroendocrine tumors are diagnosed in the laboratory because of the production of active substance or byproduct. Plasma free Metanephrine is the best test for diagnosis as the sensitivity is up to 100%.
• When we have to rule out pheochromocytoma, it's best to go for Plasma free Metanephrine. Its absence rules out pheochromocytoma. Hence, the diagnosis is made in the laboratory. And now, localization has to be done.
• MRI is the radiological Investigation of choice for:
  • Adrenal pheochromocytoma
  • Extra adrenal pheochromocytoma
  • Pheochromocytoma in pregnancy 
• The sensitivity of MRI is more than that of DOPA-PET and MIBG scan.MIBG is Meta-iodo benzyl guanidine and  it is only useful for extra adrenal pheochromocytoma. The gold standard investigation for definitive staging of pheochromocytoma: FDG-PET / PET Scan (Here the malignancy is based on metastasis).
• FNAC  are contraindicated for pheochromocytoma as they can lead to hypertensive crises.

Values are particularly high in head and neck paragangliomas

Abbreviations: MIBG, metaiodobenzylguanidine; PET/CT, position emission tomography plus CT, For the biochemical tests, the ratings correspond globally to sensitivity and specificity rates as follows: ++, <80%; +++, 85-95%; and ++++, >95%.

Treatment Of Pheochromocytoma

• In order to regulate volume depletion, we have to give:
  • Crystalloids
  • Colloids
• In order to reduce the BP: Non-selective alpha blockers are given.
  • DOC: Phenoxybenzamine
• Clinical clues to look for to start beta blockers (After adequate alpha blocked):
  • Nasal stuffiness
  • Tachycardia
• Beta blockers should not be given until the patient is fully alpha blocked so as to avoid hypertensive crises that might develop due to unopposed alpha-stimulation because alpha receptors mediate the vasoconstriction and beta receptors mediate the vasodilation. If beta blockers are started before alpha blockers are given, it will block the vasodilation. Hence, there will only be vasoconstriction. It means, there will be unopposed alpha action leading to severe vasoconstriction.This will ultimately increase the BP and lead to hypertensive crisis.

Hence, to avoid the hypertensive crisis or unopposed alpha action first, they should be adequately alpha blocked. After that, beta blockers can be administered.

The tumor in the case of pheochromocytoma is in the adrenal gland. Hence, the treatment of choice is Adrenalectomy. Laparoscopic adrenalectomy can be performed for tumors with size < 5 cm.

Malignant Pheochromocytoma

In adrenal tumors, the risk of malignancy increases with the increase in size. In Malignant Pheochromocytoma, there will be increased expression of p53, BCL-2 and tumors have activated Telomerase. Diagnosis of malignancy is based on Metastasis. It has increased secretion of dopamine and Homovanillic acid. Hence, it can be identified as malignant tumor.

Treatment

After resection, chemotherapy has to be given.

• The chemotherapy regimen given in the case of malignant pheochromocytoma (Mnemonics: “VAD”):
  • V: Vincristine
  • C: Cyclophosphamide
  • D: Dacarbazine 

Prognosis Of Pheochromocytoma

If the Pheochromocytoma is treated, the prognosis (outlook) is usually favourable. 90% of pheochromocytomas are surgically effectively eliminated.

Pheochromocytomas have the potential to result in serious, potentially fatal consequences, such as:

• Cardiomyopathy
• Myocarditis, or inflammation of the heart muscle.
• Brain hemorrhaging refers to uncontrolled bleeding.
• Pulmonary edema.
• A myocardial infarction (heart attack) or stroke may also be possible in some pheochromocytoma patients.

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