Pheochromocytoma

Epidemiology

Demographics

  • Average Age at Time of Diagnosis: 47 y/o (J Am Coll Surg, 2009) [MEDLINE]

Physiology

Mechanisms

  • Catecholamine Secretion by Pheochromocytoma
    • Dopamine
    • Epinephrine
    • Norepinephrine
  • Increased Central Sympathetic Activity: may play a role

Physiologic Effects

  • α-Adrenergic Effects
    • Vasoconstriction
  • β-Adrenergic Effects
    • Tachycardia
    • Vasodilation
  • Inhibition of Renin-Agiotensin-Aldosterone Axis
    • Plasma Volume Contraction

Malignant Pheochromocytoma

  • Approximately 10% of All Catecholamine-Secreting Tumors (Pheochromocytomas and Catecholamine-Secreting Paragangliomas) are Malignant
    • Malignancy is Only Manifested by Local Invasion or Distant Metastases: metastases can occur as long as 20 yrs after resection of the primary malignant tumor

Diagnosis

Abdominal/Pelvic CT (see Abdominal-Pelvic Computed Tomography, [[Abdominal-Pelvic Computed Tomography]])

  • General Comments
    • Approximately 95% of Catecholamine-Secreting Tumors are Located in the Abdomen
      • Approximately 85-90% of These are Adrenal (Called Pheochromocytoma): 5-10% of these are multiple
      • Approximately 10-15% of These are Extra-Adrenal (Called Catecholamine-Secreting Paraganglioma)
  • Findings
    • Adrenal Mass
      • Average Tumor Size at the Time of Diagnosis: 4.9 cm (J Am Coll Surg, 2009) [MEDLINE]

Urinary Catecholamines and Metanephrines

  • xxxx

Plasma Metanephrines

  • xxx

Clinical Manifestations

General Comments

  • Classical Clinical Triad: the full triad of clinical findings is present in only a minority of cases
  • Paroxysmal Nature of Symptoms
    • When Symptoms are Present, They are Usually Paroxysmal
  • Asymptomatic Cases
    • Symptoms are Present in 50% of Cases
    • Asymptomatic Cases May Be Diagnosed by Discovery of an Adrenal Mass, During Familial Screening, or at Autopsy

Cardiovascular Manifestations

  • Hypertension (see Hypertension, [[Hypertension]])
    • Epidemiology
      • Distribution
        • Approximately 50% of Cases Have Paroxysmal Hypertension
        • Approximately 35-45% of Cases Have Primary Hypertension (Which Presents Similarly to Essential Hypertension): these patients may also manifesta paroxysmal symptoms
        • Approximately 5-15% of Cases are Normotensive: the frequency of normotension is higher in cases with adrenal incidentalomas or those diagnosed through familial screening
      • Paroxysmal Hypertension/Tachycardia/Arrhythmia May Occur During Procedures (Colonoscopy, etc), After Induction of General Anesthesia, After Eating Foods/Beverages Containing Tyramine, or with Specific Medications (Metoclopramide, Monoamine Oxidase Inhibitors)
  • Orthostatic/Episodic Hypotension (see Hypotension, [[Hypotension]])
    • Epidemiology: occurs in some cases
    • Clinical Patterns
      • Episodic Hypotension: in rare cases where the tumor secretes only epinephrine
      • Pattern of Rapid Cyclic Fluctuation Between Hypertension and Hypotension (Cycling Every 7-15 min): unclear mechanism
      • Orthostatic Hypotension: due predominantly to decreased plasma volume
  • Palpitations (see Palpitations, [[Palpitations]])
    • Epidemiology:
  • Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])
    • Epidemiology: xxx
  • Takotsubo Cardiomyopathy (Stress-Induced Cardiomyopathy) (see Takotsubo Cardiomyopathy, [[Takotsubo Cardiomyopathy]])
    • Epidemiology: case reports (Endocr Pract, 2008) [MEDLINE]

Dermatologic Manifestations

  • Diaphoresis (see Diaphoresis, [[Diaphoresis]])
    • Epidemiology: occurs in 60-7% of symptomatic cases
  • Pallor
    • Epidemiology: seen in some cases

Endocrinologic Manifestations

  • Adrenal Mass (see Adrenal Mass, [[Adrenal Mass]])
  • Hyperglycemia/Insulin Resistance (seeHyperglycemia, [[Hyperglycemia]])
    • Epidemiology: seen in some cases
    • Physiology: due to increased catecholamine production

Gastrointestinal Manifestations

  • Constipation (see Constipation, [[Constipation]])
    • Epidemiology: seen in some cases
  • Weight Loss (see Weight Loss, [[Weight Loss]])
    • Epidemiology: seen in some cases

Hematologic Manifestations

  • Increased Erythrocyte Sedimentation Rate (ESR) (see Increased Erythrocyte Sedimentation Rate, [[Increased Erythrocyte Sedimentation Rate]])
    • Epidemiology: seen in some cases
  • Leukocytosis (see Leukocytosis, [[Leukocytosis]])
    • Epidemiology: seen in some cases
  • Polycythemia (see Polycythemia, [[Polycythemia]])
    • Epidemiology: seen in some cases
    • Physiology: due to increased erythropoietin production

Neurologic Manifestations

  • Episodic Headache (see Headache, [[Headache]])
    • Epidemiology: present in 90% of symptomatic patients
    • Clinical
      • May be Mild or Severe
      • Variable Duration
  • Generalized Weakness (see Weakness, [[Weakness]])
    • Epidemiology: seen in some cases
  • Panic Attacks (see Panic Attack, [[Panic Attack]])
    • Epidemiology: seen in some cases
    • Physiology: in cases where the pheochromocytoma produces epinephrine
  • Papilledema (see Papilledema, [[Papilledema]])
    • Epidemiology: seen in some cases
  • Psychiatric Disorders
    • Epidemiology: seen in some cases
  • Tremor (see Tremor, [[Tremor]])
    • Epidemiology: seen in some cases

Ophthlamologic Manifestations

  • Blurred Vision (see Blurred Vision, [[Blurred Vision]])
    • Epidemiology: seen in some cases

Pulmonary Manifestations

  • Dyspnea (see Dyspnea, [[Dyspnea]])
    • Epidemiology: seen in some cases
  • Posterior Mediastinal Mass (see Mediastinal Mass, [[Mediastinal Mass]])
    • Epidemiology: xxx

Renal Manifestations

  • Polydipsia (see xxxx, [[xxxx]])
    • Epidemiology: seen in some cases
  • Polyuria (see xxxx, [[xxxx]])
    • Epidemiology: seen in some cases

Treatment

Management of Hypertensive Emergency

Agents

  • Nicardipine (Cardene) (see Nicardipine, [[Nicardipine]])
    • Pharmacology: calcium channel blocker
  • Phentolamine (see Phentolamine, [[Phentolamine]])
    • Pharmacology: nonselective α-blocker
  • Phenoxybenzamine (see Phenoxybenzamine, [[Phenoxybenzamine]])
    • Pharmacology: irreversible, long-acting, nonselective α-blocker
  • Nitroprusside (Nipride) (see Nitroprusside, [[Nitroprusside]])
    • Pharmacology: xxx

Pre-Operative Preparation

Goals

  • Blood Pressure Control and Volume Expansion

Regimen

  • Phenoxybenzamine (see Phenoxybenzamine, [[Phenoxybenzamine]])
    • Pharmacology
      • Irreversible, Long-Acting (Half-Life: 24 hrs) Nonselective α-Adrenergic Blocker
      • Normalizes Blood Pressure and Expands the Contracted Plasma Volume
    • Dose: start 10 mg PO qday-BID, then increase by 10-20 mg qday (in divided doses) every 2-3 days to control blood pressure and episodic symptoms
    • Start 14 Days Preoperatively: longer preoperative lead time is required in patients with recent myocardial infarction, catecholamine cardiomyopathy, refractory hypertension, or catecholamine-induced vasculitis
      • Monitor Blood Pressure Closely: general target BP <120/80 (sitting) with SBP >90 (standing)
    • Alternative Agents
      • Doxazosin (xxx) (see Doxazosin, [[Doxazosin]])
      • Prazosin (xxx) (see Prazosin, [[Prazosin]])
      • Terazosin (xxx) (see Terazosin, [[Terazosin]])
  • High Sodium Diet (>5g/day)
    • Pharmacology: expands plasma volume (reversing the catecholamine-induced volume contraction)
    • Start on Second-Third Day of α-Blocker Therapy
      • May Be Contraindicated in Patients with Congestive Heart Failure or Chronic Kidney Disease
  • β-Blockers (see β-Adrenergic Receptor Antagonists, [[β-Adrenergic Receptor Antagonists]])
    • Dose: start low dose, titrating up gradually to control tachycardia (goal heart rate: 60-80)
    • Start Only After α-Blockade Has Been Achieved: usually 2-3 days preoperatively
      • Never Start Prior to α-Blockade, Due to the Potential to Precipitate Worsening Hypertension
      • May Be Contraindicated in Patients with Congestive Heart Failure or Asthma/COPD

Alternative Regimens

  • Calcium Channel Blockers (see Calcium Channel Blockers, [[Calcium Channel Blockers]]): may be used as a supplement to the above regimen or as a substitute for patients with intolerable side effects from α-blocker therapy
    • Nicardipine (Cardene) (see Nicardipine, [[Nicardipine]])
  • Metyrosine (see Metyrosine, [[Metyrosine]])
    • Alternative for Patients Who Cannot Tolerate Alpha and Beta Blockade

Surgical Resection of Pheochromocytoma

  • xxxx

References

General

  • Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment. Surg Oncol Clin N Am. 2016 Jan;25(1):119-38. doi: 10.1016/j.soc.2015.08.006 [MEDLINE]

Diagnosis

  • Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med. 1995 Jul 15;123(2):101-9 [MEDLINE]

Treatment

  • Catecholamine-induced cardiomyopathy. Endocr Pract. 2008;14(9):1137 [MEDLINE]
  • Clinical spectrum of pheochromocytoma. J Am Coll Surg. 2009;209(6):727 [MEDLINE]
  • Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features. Endocrine. 2014 Apr;45(3):469-78. doi: 10.1007/s12020-013-0007-y. Epub 2013 Jul 2 [MEDLINE]
  • Pheochromocytoma resection: Current concepts in anesthetic management. J Anaesthesiol Clin Pharmacol. 2015 Jul-Sep;31(3):317-23. doi: 10.4103/0970-9185.161665 [MEDLINE]
  • Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment. Surg Oncol Clin N Am. 2016 Jan;25(1):119-38. doi: 10.1016/j.soc.2015.08.006 [MEDLINE]