Pheochromocytomas and paragangliomas are catecholamine-producing tumors that can cause hypertension, and their removal can prevent potentially lethal hypertensive crises. Diagnosis is based on the measurement of catecholamines and imaging to locate the tumor, with elevated catecholamine and metanephrine levels indicating a high likelihood of pheochromocytoma. Treatment involves tumor removal and medical management to control blood pressure, including the use of α-adrenergic blockers and possibly β-blockers.

1. Pheochromocytoma
Javad ghahremani
Medical student at shahid beheshti university

2. Introduction:
 Pheochromocytomas and paragangliomas are
catecholamine- producing tumors derived from the
sympathetic or parasympathetic nervous system.
 The diagnosis of pheochromocytomas provides a
potentially correctable cause of hypertension, and
their removal can prevent hypertensive crises that
can be lethal.

3. Epidemiology:
• Pheochromocytoma is estimated to occur in 2–8 of 1 million
persons per year
• about 0.1% of hypertensive patients harbor a
pheochromocytoma
• The mean age at diagnosis is about 40 years
• The "rule of tens" for pheochromocytomas states that about
10% are bilateral, 10% are extraadrenal, and 10% are
malignant. However, these percentages are higher in the
inherited syndromes.

4. Pathogenesis:
• Pheochromocytomas and paragangliomas are well-
vascularized tumors that arise from cells derived from the
sympathetic (e.g., adrenal medulla) or parasympathetic
(e.g., carotid body, glomus vagale) paraganglia.
• The name pheochromocytoma reflects the black-colored
staining caused by chromaffin oxidation of
catecholamines

6. Etiology:
• The etiology of sporadic pheochromocytomas
and paragangliomas is unknown.
• However, about 25% of patients have an
inherited condition, including germ-line
mutations in the RET, VHL, NF1, SDHB, SDHC,
SDHD, or SDHAF2 genes.

7. Clinical Features
Headaches
Sweating attacks
Palpitations and tachycardia
Hypertension, sustained or paroxysmal
Anxiety and panic attacks
Pallor
Nausea
Abdominal pain
Weakness
Weight loss
Paradoxical response to antihypertensive drugs
Polyuria and polydipsia
Constipation
Orthostatic hypotension
Dilated cardiomyopathy
Erythrocytosis
Elevated blood sugar
Hypercalcemia

8. Diagnosis:
• The diagnosis is based on documentation of
catecholamine excess by biochemical testing and
localization of the tumor by imaging. Both are of
equal importance, although measurement of
catecholamines is traditionally the first step.

9. Biochemical Testing:
• Pheochromocytomas and paragangliomas synthesize and store
catecholamines, which include norepinephrine (noradrenaline),
epinephrine (adrenaline), and dopamine. Elevated plasma and
urinary levels of catecholamines and the methylated
metabolites, metanephrines, are the cornerstone for the
diagnosis.
• Catecholamines and metanephrines can be measured by using
different methods
• In a clinical context suspicious for pheochromocytoma, when
values are increased three times the upper limit of normal, a
pheochromocytoma is highly likely regardless of the assay used.

10. Biochemical and Imaging Methods Used for Pheochromocytoma and
Paraganglioma Diagnosis
Diagnostic Method Sensitivity Specificity
24-h urinary tests
Vanillylmandelic acid ++ ++++
Catecholamines +++ +++
Fractionated metanephrines ++++ ++
Total metanephrines +++ ++++
Plasma tests
Catecholamines +++ ++
Free metanephrines ++++ +++
CT ++++ +++
MRI ++++ +++
MIBG scintigraphy +++ ++++
Somatostatin receptor
scintigraphy*
++ ++
Dopa (dopamine) PET +++ ++++

11. Differential Diagnosis:
• essential hypertension
• anxiety attacks
• use of cocaine or amphetamines
• mastocytosis or carcinoid syndrome (usually lacking hypertension)
• intracranial lesions
• clonidine withdrawal
• autonomic epilepsy
• factitious crises (usually from sympathomimetic amines).
When an asymptomatic adrenal mass is identified,
likely diagnoses other than pheochromocytoma include:
1. a nonfunctioning adrenal adenoma
2. Aldosteronoma
3. cortisol-producing adenoma (Cushing's syndrome).

12. Treatment:
• Complete tumor removal is the ultimate therapeutic goal
• α-Adrenergic blockers (phenoxybenzamine)
• liberal salt intake and hydration are necessary to avoid orthostasis
• Adequate alpha blockade generally requires 7 days, with a typical final dose of
20–30 mg phenoxybenzamine three times per day.
• Oral prazosin or intravenous phentolamine can be used to manage paroxysms
while awaiting adequate alpha blockade.
• blood pressure should be consistently below 160/90 mmHg, with moderate
orthostasis
• Beta blockers (e.g., 10 mg propranolol three to four times per day) can be added
after starting alpha blockers
• Other antihypertensives, such as calcium channel blockers or angiotensin-
converting enzyme inhibitors

13. :Resources
18th edition of Harrison's Principles of
Internal Medicine