A pheochromocytoma is a catecholamine-secreting tumor that typically develops in the adrenal medulla. Pheochromocytomas are malignant in approximately 10% of cases. Excess sympathetic nervous system stimulation in individuals with pheochromocytoma leads to episodic blood pressure crises with paroxysmal headaches, diaphoresis, heart palpitations, and pallor. Pheochromocytomas may also be asymptomatic or manifest with persistent hypertension. Elevated catecholamine metabolites in the plasma or urine confirm the diagnosis, and imaging studies are used to determine the location of the tumor. Surgical resection is the treatment of choice. Preoperative alpha-adrenergic blockade (e.g., phenoxybenzamine) is indicated to prevent intraoperative complications such as hypertensive crises.
- Pheochromocytoma: a catecholamine-producing tumor that originates from chromaffin cells in the adrenal medulla (intraadrenal) 
- Paraganglioma: a catecholamine-producing tumor that originates from chromaffin cells in the autonomic ganglia (extraadrenal) 
Pheochromocytomas and paragangliomas (PPGLs) may also be hormonally inactive in rare cases.
- The majority of pheochromocytomas are benign, unilateral, catecholamine-producing tumors, that rarely produce other hormones such as EPO.
- Tumors arise from chromaffin cells, which are derived from the neural crest.
- Localization 
- 25% of pheochromocytomas are hereditary (germline mutations):
MAry P. sang “superCALi-fragilistic-EXpiali-DOcious” to the children 10 times: 10% of pheochromocytomas are MAlignant; 10% show CALcifications; 10% are EXtra-adrenal; 10% are DUal sided, i.e., bilateral; and 10% affect children.
Clinical presentation is related to fluctuating levels of excess epinephrine, norepinephrine, and dopamine secretion, so symptoms are characterized by patterns of relapse and remitting (episodic hyperadrenergic syndrome).
- Episodic hypertension (or persistent hypertension in some cases) ; 
- Paroxysmal 
- Weight loss due to increased basal metabolism
- Signs of EPO is secreted, if
- Additional features of hereditary disorders associated with pheochromocytoma
Patients can show typical clinical features (e.g., secondary hypertension) but may also be asymptomatic.
5 most important Problems (5 P’s) of Pheochromocytoma: increased blood Pressure, head Pain (headache), Perspiration, Palpitations, and Pallor
- Consult a specialist early.
- Obtain biochemical testing to prove catecholamine excess.
- Obtain imaging to locate the tumor.
- Consider indications for genetic testing on an individual basis.
Biochemical testing 
Screening for catecholamine excess 
- Characteristic features of pheochromocytoma
- Known or suspected hereditary disorders associated with pheochromocytoma
Preferred modalities (highly sensitive): plasma free metanephrines (taken in supine position ), OR urinary fractionated metanephrines (24-hour urine collection)
- Significantly elevated metanephrines: Diagnosis is likely.
- Normal metanephrines: Diagnosis is unlikely.
- Moderately elevated metanephrines (inconclusive results)
- Repeat the initial test after removal of interfering factors. 
- If results remain inconclusive after repeat testing: Obtain a clonidine suppression test.
- Other modalities (lower diagnostic accuracy): no longer routinely recommended
Clonidine suppression test
- Indication (not routinely recommended): inconclusive results from catecholamine excess testing
- Method: normetanephrine is measured in plasma at baseline and 3 hours after oral administration of clonidine.
- Inadequate normetanephrine suppression : Diagnosis is likely.
- Adequate normetanephrine suppression : Diagnosis is unlikely. 
Obtain imaging studies only after catecholamine excess has been confirmed.
- CT abdomen and pelvis with contrast: preferred initial modality
- MRI: preferred in patients with known metastatic disease
- Functional imaging studies: Consider in select patients under specialist consultation.
- Genetic testing: Practice shared decision-making under specialist guidance. 
- Histopathology 
Pheochromocytoma is often referred to as “the great mimic” because signs and symptoms are similar to those seen in many other clinical conditions. 
Adrenocortical carcinoma 
- Definition: a rare cancer of the adrenal gland that originates in the adrenal cortex
- Rare disease; estimated annual incidence 1–2:1,000,000
- Median age at diagnosis: 50–60 years
- Signs of excessive hormone production
- Nonspecific symptoms caused by tumor growth (e.g., flank pain)
- Physical examination and patient history
- 24-hour urine test: ↑ free cortisol
- Blood tests
- MRI or CT usually shows a large (> 6 cm in diameter) tumor that may contain necrosis, calcifications, and/or hemorrhage and may have heterogeneous enhancement.
- Adrenocortical carcinomas are frequently detected as adrenal incidentalomas (a clinically inapparent adrenal mass > 1 cm in diameter that is detected on imaging performed for other reasons than a suspected adrenal condition). 
- Prognosis: depends on the stage but is generally poor (overall 5-year survival is ∼ 50%) 
- Panic disorder
- Anxiety disorders
- Recreational drugs (e.g., cocaine)
- Factitious disorder
The differential diagnoses listed here are not exhaustive.
General principles 
Multidisciplinary care at a specialized center is recommended.
- Surgical tumor resection is the only curative treatment.
- Preoperative blood pressure management and postoperative monitoring for adrenal crisis are essential.
- Management of advanced nonoperable disease (e.g., metastatic disease) is palliative and may include: 
- Patients with germline mutations should be included in surveillance programs led by endocrinologists.
Surgical resection 
- Adrenalectomy: treatment of choice for pheochromocytoma
- Removal of paragangliomas: Open resection is preferred. 
Preoperative management 
- Treatment target
Pharmacotherapy: Initiate 7–14 days prior to surgery. 
- Indicated for all patients with hormonally active pheochromocytoma
- Start with alpha-adrenergic blockade.
- Add a beta blocker after effective alpha blockade to control tachycardia, e.g.: 
- Consider the following for additional blood pressure control:
- Nonpharmacological therapy: Ensure high sodium and fluid intake to prevent postoperative hypotension. 
Treat PHEochromocytoma with PHEnoxybenzamine, but remember that Alpha blockers should be given Ahead and Beta blockers Behind.
Starting beta blockers before alpha blockers is contraindicated because doing so can cause life-threatening hypertensive crisis. Beta-blockers cancel out the vasodilatory effect of peripheral beta-2 adrenoceptors, potentially leading to unopposed alpha-adrenoceptor stimulation and thereby causing vasoconstriction and increased blood pressure.
Postoperative management 
- Postoperative monitoring
- May include repeat biochemical testing and imaging studies; see “Diagnostics.”
- The frequency of monitoring is based on individual risk for persistent, recurrent, and/or metastatic disease.