II. Definitions

  1. Pheochromocytoma
    1. CatecholamineSecreting tumor of the Adrenal Gland

III. Epidemiology

  1. Incidence: Rare
    1. Prevalence in general population: 0.05%
    2. Accounts for <1% of Hypertension cases
    3. Accounts for 5-7% of incidental Adrenal Masses on CT
  2. Peak ages: 30-60 years
  3. Equal male and female predominance

IV. Pathophysiology

  1. Pheochromocytoma distribution
    1. Adrenal (90%)
    2. Extra-adrenal (e.g. chest, Abdomen, Pelvis, head or neck)

V. Presentation: Classic Episodes

  1. Predominant Symptoms
    1. Headache
    2. Diaphoresis or Sweating
    3. Palpitations
  2. Associated Symptoms
    1. Anxiety
    2. Tremor
    3. Pallor
    4. Chest Pain
    5. Epigastric Pain
    6. Flushing (rare)
    7. Painless Hematuria (rare)
    8. Orthostatic Hypotension and Syncope
    9. Labile Blood Pressure
  3. Timing of episodes
    1. Duration: One hour or less
    2. Frequency: daily to once every few months

VI. Presentation: Other

  1. Hyperadrenergic spells (see classic episodes above)
  2. Resistant Hypertension
  3. Malignant or intra-operative Hypertension
  4. Family History of Pheochromocytoma or predisposing syndromes (e.g. MEN 2, NF1, VHL. SDH)
  5. Premature Hypertension (age under 20 years)
  6. Idiopathic Dilated Cardiomyopathy

VII. Diagnostic Clues

  1. Six "H's"
    1. Hypertension
    2. Headache - throbbing (90%)
    3. Hyperhidrosis or excessive sweating (69%)
    4. Heart consciousness or Palpitations (73%)
    5. Hypermetabolism
    6. Hyperglycemia
  2. Rule of 10
    1. Familial (10%, e.g. multiple endocrine neoplasia)
    2. Malignant (10%)
    3. Multiple or Bilateral (10%)
    4. Extra-adrenal (10%)
    5. Childhood onset (10%)
    6. Recurrence after Surgery (10%)

VIII. Differential Diagnosis

  1. Primary Aldosteronism
  2. Carcinoid
  3. Accelerated or Malignant Hypertension
  4. Illicit, OTC or prescribed Sympathomimetic medications
  5. Chemodectoma
  6. Ganglioneuroma
  7. Thyrotoxicosis
  8. Menopause
  9. Panic Disorder
  10. Antihypertensive withdrawal (e.g. Clonidine Withdrawal)

IX. Labs: Preparation

  1. Stop any interfering medications
    1. Labetalol (stop for 1 week)
    2. Tricyclic Antidepressant (stop for 2 weeks)
    3. Psychoactive medications (stop for weeks)
    4. Levodopa or Methyldopa
    5. Decongestants
    6. Benzodiazepines
    7. Muscle relaxants (mephenasin, Methocarbamol)
    8. Avoid Tylenol for 48 hours
    9. Avoid Aspirin
  2. Stop other interfering agents
    1. No Caffeine, Alcohol or Tobacco for 4 hours
    2. Tomatoes
    3. Walnuts
    4. Pineapple
    5. Banana
    6. Eggplant
    7. Avocado
    8. Plums

X. Labs: Available Tests

  1. Best studies
    1. Urine Metanephrines (24 hour collections)
      1. Use as first line screening
      2. Test Sensitivity: 76%
      3. Test Specificity: 94%
    2. Plasma Free Metanephrines
      1. Very high False Positive Rate (Pheochromocytoma is rare)
      2. Use only for confirmation, not for screening
      3. Test Sensitivity: 99%
      4. Test Specificity: 89%
  2. Tests with lower efficacy
    1. Urinary VMA
      1. Normal value under 6.5 mg/day
      2. Imprecise test
      3. Drugs and food interfere with test
      4. Test Sensitivity: 63%
      5. Test Specificity: 94%
    2. Plasma Catecholamines (Norepinephrine, Epinephrine)
      1. Test Sensitivity: 85%
      2. Test Specificity: 80%

XI. Labs: Protocol

  1. First: 24-hour Urine Metanephrine and Urine VMA
  2. Next: Plasma Free Metanephrines
  3. Next: Plasma Catecholamines (equivocal metanephrines)
  4. Final: Clonidine Suppression (positive Catecholamines)

XII. Imaging: Tumor localization

  1. Abdominal CT with and without contrast
    1. Precautions
      1. Ionic Iodinated contrast is a risk for Hypertensive Emergency, but nonionic contrast is safe
        1. Bessell-Browne (2007) AJR Am J Roentgenol 188:970-4 [PubMed]
    2. Interpretation
      1. Incidental non-contrast CT Adrenal Mass with hounsfield density <10 excludes Pheochromocytoma
        1. Test Sensitivity: 99.6%
        2. Buitenwerf (2018) Eur J Endocrinol 178:431-7 [PubMed]
    3. Efficacy
      1. Test Sensitivity: 90%
      2. Test Specificity: 93%
  2. Adrenal MRI
    1. Test Sensitivity: 93%
    2. Test Specificity: 93%
  3. SPECT I-123 MIBG Scan (single photon emission, Iodine-131 metaiodobenzyl-guanidine)
    1. Test Sensitivity: 77 to 91%
    2. Test Specificity: 95 to 100%
    3. Good for looking for tumors in unusual sites
    4. Injection of radioisotope is 1-3 days before imaging

XIII. Management

  1. Preoperative Medical Management
    1. Alpha Adrenergic ReceptorAntagonist (2 weeks pre-op)
      1. Phenoxybenzamine (alpha blocker) orally twice daily
      2. Phentolamine IV prn
    2. Beta Blocker (only start after alpha blockade)
      1. Propranolol orally four times daily
      2. Precaution
        1. Only use if already on alpha-adrenergic blocker
        2. Otherwise, risk of worsening Hypertension from unopposed alpha stimulation
  2. Surgical Management
    1. Laparoscopic adrenalectomy Indications
      1. Single, small adrenal tumors
      2. Hypertension controlled
    2. Open Adrenalectomy
      1. Adrenal tumor size over 7 cm
  3. Intra-Operative Management
    1. Continuous Arterial-line Blood Pressure Monitoring
    2. Treat Hypotension
      1. Fluid management
      2. Consider pressor support
    3. Treat Hypertension
      1. Phentolamine
      2. Nitroprusside
    4. Treat Tachycardia or ectopy
      1. Beta Blocker
  4. Adjunctive treatment for malignant Pheochromocytoma
    1. Chemotherapy
      1. Cyclophosphamide
      2. Dacarbazine
      3. Vincristine
    2. MIGB (metaiodobenzyl-guanidine I-131)
    3. Metyrosine 1 gram every 6 hours
      1. Depletes tumor Catecholamine stores

XIV. Course

  1. Persistent Hypertension in 25% of treated patients

XV. Monitoring

  1. Screen Urine Metanephrines annually
  2. Screen Urine Catecholamines annually

XVI. References

  1. Bailey (2001) CMEA Medicine Lecture, San Diego
  2. Broder (2020) Crit Dec Emerg Med 34(12): 14
  3. (Feb 2001) Ann Intern Med

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Related Studies

Ontology: Pheochromocytoma (C0031511)

Definition (CHV) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA
Definition (CHV) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA
Definition (CHV) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA
Definition (CHV) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA
Definition (CHV) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA
Definition (MEDLINEPLUS)

Pheochromocytoma is a rare tumor that usually starts in the cells of one of your adrenal glands. Although they are usually benign, pheochromocytomas often cause the adrenal gland to make too many hormones. This can lead to high blood pressure and cause symptoms such as

  • Headaches
  • Sweating
  • Pounding of the heart
  • Being shaky
  • Being extremely pale

Sometimes pheochromocytoma is part of another condition called multiple endocrine neoplasia syndrome (MEN). People with MEN often have other cancers and other problems involving hormones.

Doctors use lab tests and imaging tests to diagnose it. Surgery is the most common treatment. Other options include radiation therapy, chemotherapy, and targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells.

NIH: National Cancer Institute

Definition (NCI_NCI-GLOSS) Tumor that forms in the center of the adrenal gland (gland located above the kidney) that causes it to make too much adrenaline. Pheochromocytomas are usually benign (not cancer) but can cause high blood pressure, pounding headaches, heart palpitations, flushing of the face, nausea, and vomiting.
Definition (NCI_CDISC) A neoplasm of the adrenal gland medulla, for which the malignancy status has not been established.
Definition (NCI) A benign or malignant neuroendocrine neoplasm of the sympathetic nervous system that secretes catecholamines. It arises from the chromaffin cells of the adrenal medulla. Clinical presentation includes headaches, palpitations, chest and abdominal pain, hypertension, fever, and tremor. Microscopically, a characteristic nesting (zellballen) growth pattern is usually seen. Other growth patterns including trabecular pattern may also be present.
Definition (MSH) A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298)
Definition (CSP) usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia; the cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
Concepts Neoplastic Process (T191)
MSH D010673
ICD10 M8700/0
SnomedCT 302835009, 154555009, 188337000, 360332001, 360335004, 269615000, 85583005, 399343007
English Pheochromocytomas, Adrenal Medullary Paraganglioma, Adrenal Medullary Pheochromocytoma, Adrenal Pheochromocytoma, Intraadrenal Paraganglioma, Chromaffin Paraganglioma of the Adrenal Gland, Adrenal Gland Chromaffin Paraganglioma, Adrenal Gland Chromaffinoma, Adrenal Gland Paraganglioma, Adrenal Gland Pheochromocytoma, PHEOCHROMOCYTOMA, Pheochromocytoma, adrenal, [M]Phaeochromocytoma NOS, [M]Pheochromocytoma NOS, Phaeochromocytoma NOS, Pheochromocytoma NOS, chromaffinoma, Pheochromocytoma [Disease/Finding], chromaffin tumor, pheochromocytoma syndrome, pheochromocytomas, phaeochromocytoma, Chromaffin paraganglioma (disorder), ADRENAL GLAND CHROMAFFIN PARAGANGLIOMA, ADRENAL MEDULLARY PHEOCHROMOCYTOMA, Pheochromocytoma (adrenal), CHROMAFFIN PARAGANGLIOMA OF THE ADRENAL GLAND, INTRAADRENAL PARAGANGLIOMA, ADRENAL GLAND CHROMAFFINOMA, PCC, PHEOCHROMOCYTOMA, UNDETERMINED, PHAEOCHROMOCYTOMA, ADRENAL MEDULLARY PARAGANGLIOMA, ADRENAL PHEOCHROMOCYTOMA, ADRENAL GLAND PARAGANGLIOMA, pheochromocytoma (diagnosis), pheochromocytoma, adrenal neoplasm of uncertain behavior pheochromocytoma, Chromaffin paraganglioma, Chromaffin tumor, Chromaffinoma, Chromaffin tumour, Phaeochromocytoma, Chromaffinoma (disorder), Adrenal medullary paraganglioma, Pheochromocytoma (disorder), Pheochromocytoma (morphologic abnormality), Pheochromocytoma, NOS, Phaeochromocytoma, NOS, Phaeochromocytoma (disorder), Phaeochromocytoma [Ambiguous], Pheochromocytoma
French PHEOCHROMOCYTOME, Chromaffinome, Phéochromocytome
Portuguese FEOCROMOCITOMA, Feocromocitoma Extra-Adrenal, Feocromocitoma
Spanish FEOCROMOCITOMA, paraganglioma de médula suprarrenal, paraganglioma de células argentafines (trastorno), tumor de células cromafines, paraganglioma de células argentafines, paraganglioma de células cromafines, cromafinoma (trastorno), cromafinoma, feocromocitoma (anomalía morfológica), feocromocitoma (trastorno), feocromocitoma, SAI, feocromocitoma, paraganglioma cromafín, tumor cromafín, Feocromocitoma
German PHAEOCHROMOZYTOM, Phaeochromozytom, Phäochromozytom
Swedish Feokromocytom
Japanese カッショクサイボウシュ, 褐色細胞腫, かっ色細胞腫, クロム親和細胞腫, クロム親和性細胞腫, 髄質細胞腫, 好クロム性細胞腫
Czech feochromocytom, Feochromocytom
Finnish Feokromosytooma
Polish Przyzwojak chromochłonny, Guz chromochłonny nadnerczy, Pheochromocytoma, Barwiak
Hungarian Phaeochromocytoma, Phaeocromocytoma
Norwegian Feokromocytom
Dutch feochromocytoom, Feochromocytoom
Italian Feocromocitoma

Ontology: Paroxysmal hypertension (C0221154)

Concepts Sign or Symptom (T184)
SnomedCT 23130000
Dutch paroxysmale hypertensie
French Hypertension paroxystique
German Hypertonie, paroxysmal
Italian Ipertensione parossistica
Portuguese Hipertensão paroxística
Spanish Hipertensión paroxística, hipertensión arterial paroxística (trastorno), hipertensión arterial paroxística
Japanese 発作性高血圧, ホッサセイコウケツアツ
English paroxysmal hypertension (physical finding), paroxysmal hypertension, paroxysmal hypertension was observed, Hypertension paroxysmal, Paroxysmal hypertension, Paroxysmal hypertension (disorder), Paroxysmal Hypertension
Czech Paroxysmální hypertenze
Hungarian Paroxysmalis hypertonia