Pheochromocytoma (Crisis)

Pheochromocytoma crisis is a life-threatening endocrine emergency defined as the acute, severe presentation of catecholamine-induced hemodynamic instability causing end-organ damage or dysfunction, with a mortality rate of approximately 14–27%. [1-2] It occurs in 7–18% of patients with pheochromocytoma/paraganglioma (PPGL) and may be the first clinical manifestation of an undiagnosed tumor. [3-4]

• Classic triad (present in only ~24% of patients): severe headache, palpitations, and diaphoresis [5]
• Paroxysmal or sustained hypertension with episodes of headache, sweating, anxiety, tremor, pallor, nausea/vomiting, and abdominal pain [3][5]
• Timing: Paroxysmal episodes may last minutes to hours; crisis onset is often sudden
• Triggers to ask about: recent surgery, anesthesia, trauma, new medications (especially metoclopramide, beta-blockers, corticosteroids), pregnancy (third trimester/peripartum), physical exertion [3]
• Headache was the most common symptom in a 200-case review (39.5%); nausea and vomiting were significantly associated with higher mortality [1]
• Ask about prior episodes of paroxysmal hypertension, "spells," or unexplained tachycardia
• Important negatives: absence of illicit drug use (cocaine, amphetamines), absence of MAO inhibitor use

• BP ≥180/120 mmHg with evidence of end-organ damage [4]
• Rapidly alternating hypertension and hypotension (hemodynamic lability) [3][6]
• Acute pulmonary edema / flash pulmonary edema [6]
• Chest pain with troponin elevation (catecholamine cardiomyopathy or ACS mimic) [7-8]
• Temperature >40°C with encephalopathy (pheochromocytoma multisystem crisis [PMC]) [6]
• Unexplained cardiogenic shock, especially in a young patient without coronary disease [2][6]
• Lactic acidosis, multi-organ failure, unexplained hyperglycemia [6]
• Cardiac arrest [9]

Crisis-precipitating drugs (AVOID): [3][10]

• Metoclopramide and other dopamine antagonists (D2 blockade triggers catecholamine release)
• Beta-blockers without prior alpha-blockade (causes unopposed alpha stimulation → worsening hypertension) [3]
• Labetalol — alpha-blocking effect is insufficient relative to beta-blockade; can paradoxically worsen crisis [3-4][11]
• Glucagon, sympathomimetics, corticosteroids/synthetic ACTH, tricyclic antidepressants [3]
• General anesthetics, neuromuscular blockers, opiates [12]

Acute crisis treatment: [13-14]

• IV phentolamine 5 mg bolus, repeat q10 min PRN (first-line for catecholamine excess per 2025 AHA/ACC guidelines) [14-15]
• IV nicardipine 5 mg/h, titrate by 2.5 mg/h q5 min (max 15 mg/h) — widely available alternative [14]
• IV nitroprusside 0.3–0.5 mcg/kg/min for refractory hypertension [13-14]
• IV clevidipine — another option per 2025 AHA/ACC for catecholamine excess states [14]
• Esmolol or lidocaine for cardiac arrhythmias — only after adequate alpha-blockade [12-13]
• IV magnesium sulfate — adjunctive for BP and arrhythmia control [3]
• Avoid IV hydralazine (cardiostimulatory, unpredictable) and IV diuretics (unless overt heart failure) [4]

Chronic/preoperative alpha-blockade: [13][16]

• Phenoxybenzamine 10 mg PO BID, titrate up to 30 mg TID
• Doxazosin 1 mg PO daily, titrate up to 10 mg BID
• Beta-blockade added ONLY after adequate alpha-blockade for reflex tachycardia

• High-sodium diet (~5000 mg/day) and generous fluid intake (~2.5 L/day) during preoperative alpha-blockade to counteract catecholamine-induced volume contraction [16]
• Avoid tyramine-rich foods (aged cheeses, cured meats, fermented foods, red wine) — tyramine displaces catecholamines from vesicular storage and can precipitate crisis [12]
• Acute crisis: NPO; IV fluid resuscitation is critical given chronic intravascular volume depletion [3-4]

• Cardiovascular: chest pain, palpitations, dyspnea on exertion, orthopnea, syncope
• Neurologic: headache, visual changes, altered mental status, seizures
• GI: nausea, vomiting, abdominal pain, constipation (catecholamine-mediated ileus)
• Endocrine: weight loss, heat intolerance, hyperglycemia symptoms
• Renal: decreased urine output
• Constitutional: diaphoresis, pallor (not flushing — pallor is characteristic), anxiety, tremor

• Family history of PPGL, medullary thyroid carcinoma, hyperparathyroidism, renal cell carcinoma, hemangioblastomas, neurofibromas [13][16]
• Personal or family history of genetic syndromes: MEN2, VHL, NF1, SDHx mutations [13][16]
• Up to 40% of PPGLs harbor germline pathogenic variants — the highest rate of any solid tumor [17]
• Ask about prior adrenal incidentalomas, prior "spells" dismissed as panic attacks
• Social context: pregnancy status (crisis risk increases in third trimester) [3]

• Hereditary syndromes (account for ~25–40% of cases): [5][17]
  • MEN2 (RET): PCC in up to 50%, bilateral tumors common
  • VHL: PCC/PGL in 10–20%, earliest age at diagnosis
  • SDHx (SDHB, SDHD, SDHC, SDHA): highest metastatic risk (especially SDHB)
  • NF1: PCC in ~3%
  • TMEM127, MAX
• Young age at presentation (<45 years) [5]
• Bilateral or extra-adrenal tumors [16]
• Tumor hemorrhage or infarction (spontaneous or traumatic) [3]
• Surgical manipulation, anesthesia induction, pregnancy [3]
• Undiagnosed/untreated PPGL undergoing any surgical procedure [18]

• Acute coronary syndrome / STEMI — pheochromocytoma can mimic ACS with ST changes, troponin elevation, and wall motion abnormalities but with normal coronary arteries [7-8]
• Takotsubo (stress) cardiomyopathy — PPGL-related TTS has higher rates of cardiogenic shock (34% vs 4%) and heart failure (47% vs 18%) than non-PPGL TTS [19]
• Thyroid storm — tachycardia, hyperthermia, altered mental status
• Cocaine/amphetamine toxicity — sympathomimetic crisis
• Malignant hypertension from other causes
• Serotonin syndrome or neuroleptic malignant syndrome — hyperthermia, rigidity, autonomic instability
• Carcinoid crisis — flushing (vs pallor in pheo), diarrhea, bronchospasm
• Acute myocarditis from other etiologies
• Septic shock — if presenting with hypotension and multi-organ failure
• Aortic dissection — severe hypertension with tearing chest/back pain

• Prior episodes of paroxysmal hypertension or "spells"
• Known adrenal mass or incidentaloma
• Previous pheochromocytoma resection (recurrence risk)
• History of genetic syndrome components (MTC, hyperparathyroidism, retinal hemangioblastomas, neurofibromas, renal cell carcinoma) [13]
• Prior anesthetic complications or intraoperative hypertensive crises
• Chronic hypertension refractory to standard therapy

Vital signs

• Severe hypertension (often >200/120 mmHg) or labile BP with alternating hypertension/hypotension [3][6]
• Tachycardia (or paradoxical bradycardia)
• Hyperthermia (>40°C in PMC) [6]

Focused exam

• Pallor (not flushing — catecholamine-mediated vasoconstriction) [5]
• Diaphoresis, tremor, anxiety
• Cardiac: S3 gallop, pulmonary crackles (acute heart failure), new murmur
• Abdominal: palpable mass (rare; avoid vigorous palpation — can trigger catecholamine surge)
• Neurologic: altered mental status, focal deficits (stroke), papilledema
• Skin: café-au-lait spots, neurofibromas (NF1), mucosal neuromas (MEN2B) [13][16]
• Marfanoid habitus (MEN2B) [16]

Diagnostic: [3][5][13]

• Plasma free metanephrines (preferred in acute setting — sensitivity >96%)
• 24-hour urine fractionated metanephrines and catecholamines (if patient stabilized)
• Levels in crisis are typically extremely elevated (mean 23× upper limit of normal in one series) [3]

Assess end-organ damage

• Troponin (catecholamine cardiomyopathy, demand ischemia)
• BNP/NT-proBNP (heart failure)
• BMP/CMP (renal function, hyperglycemia, electrolytes)
• Lactate (lactic acidosis — common in severe crisis) [6]
• CBC, coagulation studies
• Liver function tests (hepatic injury in multi-organ failure)
• Blood glucose (hyperglycemia is characteristic; hypoglycemia may occur post-resection) [13]

• Serial troponin, lactate, renal function
• Glucose monitoring (especially perioperatively)

• CT abdomen/pelvis with IV contrast — first-line to identify adrenal mass; diagnostic in 33/34 ICU patients in one series. Low-osmolar contrast does not appreciably trigger catecholamine release [2-3]
• MRI abdomen — preferred for paragangliomas, pediatric patients, pregnant patients, and surveillance
• Bedside ultrasound — may identify adrenal mass in unstable patients too ill to transport [3]
• CT head — if neurologic symptoms (rule out hemorrhagic/ischemic stroke)
• CT angiography chest — if aortic dissection or pulmonary embolism suspected [20]
• Functional imaging (¹²³I-MIBG, ⁶⁸Ga-DOTATATE PET/CT) — not indicated acutely; used for staging and metastatic workup after stabilization [21]

• Echocardiography — critical in crisis; median LVEF 30% in ICU cohort. Assess for Takotsubo pattern (apical ballooning or inverted/basal pattern, which is more common in PPGL-related TTS), dilated cardiomyopathy, or regional wall motion abnormalities [2][19]
• Coronary angiography — if ACS suspected; typically shows normal coronary arteries in catecholamine cardiomyopathy [7-8]
• Genetic testing — recommended for ALL patients with PCC/PGL per NCCN guidelines [13]
• SOFA/SAPS II scoring — for ICU severity stratification [2]

ECG findings in pheochromocytoma crisis: [7][19]

• Sinus tachycardia (most common arrhythmia)
• ST-segment elevation or depression mimicking acute MI
• T-wave inversions (diffuse or regional)
• Prolonged QTc (risk for torsades de pointes)
• Low voltage QRS
• Atrial fibrillation/flutter
• Ventricular tachycardia (life-threatening)
• Bradyarrhythmias (less common)

Key pearl: ECG changes mimicking STEMI with elevated troponin but normal coronary arteries should raise suspicion for pheochromocytoma, especially in younger patients without traditional cardiovascular risk factors. [8][22]

Severity classification (Whitelaw et al.): [3]

• Type A crisis: Hemodynamic instability without sustained hypotension (4× more common)
• Type B crisis: Sustained hypotension, shock, and multi-organ dysfunction (higher mortality)
• Pheochromocytoma multisystem crisis (PMC): Hyperthermia + multi-organ failure + encephalopathy + labile BP (19% of all crisis cases, highest mortality) [1]

The heart is the most commonly damaged organ (99%), followed by lungs (44%) and kidneys (21.5%). [1] Cardiovascular complications include catecholamine cardiomyopathy (up to 11%), Takotsubo syndrome, acute MI, arrhythmias, pulmonary edema, and aortic dissection. [6][23-24] The adrenergic phenotype (epinephrine-secreting) is more associated with Takotsubo and tachyarrhythmias, while the noradrenergic phenotype is more associated with atherosclerotic complications and flash pulmonary edema. [4][25]

Initial stabilization: [3-4][13-14]

• ICU admission with continuous arterial BP monitoring and telemetry
• IV fluid resuscitation — aggressive volume expansion (chronic intravascular depletion from catecholamine-mediated vasoconstriction)
• IV alpha-blockade first:
  • Phentolamine 5 mg IV bolus q10 min PRN (max 50 mg/24h) [14]
  • OR nicardipine 5–15 mg/h IV infusion [14]
  • OR nitroprusside 0.3–10 mcg/kg/min for refractory hypertension [13]
• Beta-blockade ONLY after adequate alpha-blockade — esmolol preferred (short-acting, titratable) for tachyarrhythmias [3][13]
• Arrhythmia management: esmolol or lidocaine for ventricular arrhythmias; magnesium sulfate as adjunct [3][13]
• Cardiogenic shock: consider VA-ECMO as bridge to recovery — survival rate ~93.5% in published series with full LVEF recovery in survivors; Impella or other mechanical circulatory support [26]
• CRRT — for catecholamine removal and acute kidney injury [9]

BP targets: Reduce SBP by ~25% in the first hour, then gradually to <140 mmHg over 24–48 hours. [14] Avoid aggressive lowering to <120 mmHg in the first hour (unlike aortic dissection).

Definitive treatment: Surgical resection after medical stabilization with 7–14 days of alpha-blockade, volume repletion, and high-salt diet. [13][16] Emergency adrenalectomy carries significant morbidity and should be avoided if possible. [18]

The NCCN algorithm for pheochromocytoma management is shown below:

• All pheochromocytoma crises require ICU admission [2]
• Admission criteria: any hemodynamic instability, end-organ damage, arrhythmia, cardiomyopathy, multi-organ dysfunction
• VA-ECMO should be considered early in refractory cardiogenic shock [2][26]
• Urgent/emergent adrenalectomy only if medical management fails and patient is deteriorating despite maximal support [18]
• Endocrinology, cardiology, and surgical (endocrine surgery or urology) consultation
• Transfer to a center with ECMO capability if cardiogenic shock is refractory

• Postoperative monitoring: Watch for hypotension (loss of catecholamine drive) and hypoglycemia (rebound insulin effect) — treat with IV fluids and dextrose [13]
• After resection, repeat plasma/urine metanephrines at 2–6 weeks to confirm biochemical cure
• Long-term surveillance: annual biochemical screening (metanephrines) lifelong, as recurrence can occur years later [13]
• Genetic testing and counseling for all patients — up to 40% have germline mutations [13][17]
• If hereditary syndrome confirmed, initiate syndrome-specific surveillance for patient and at-risk family members (per NCCN) [13]
• Medical alert ID recommended for patients with hormonally secreting tumors in situ or metastatic disease [13]
• Return precautions: recurrent headache, palpitations, diaphoresis, chest pain, severe hypertension, visual changes, or any "spell" — seek immediate evaluation

1. Clinical Characteristics and Outcomes of Pheochromocytoma Crisis: A Literature Review of 200 Cases. — Ando Y, Ono Y, Sano A, et al. Journal of Endocrinological Investigation. 2022.

2. Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation. — Sauneuf B, Chudeau N, Champigneulle B, et al. Critical Care Medicine. 2017.

3. Phaeochromocytoma crisis. — Whitelaw BC, Prague JK, Mustafa OG, et al. Clinical Endocrinology. 2014.

4. Catecholamine-Induced Hypertensive Crises: Current Insights and Management. — Nazari MA, Hasan R, Haigney M, et al. The Lancet. Diabetes & Endocrinology. 2023.

5. Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options. — Eid M, Foukal J, Sochorová D, et al. Cancer Medicine. 2023.

6. Diagnosing phaeochromocytoma/­paraganglioma in a patient presenting with critical illness: biochemistry versus imaging. — Amar L, Eisenhofer G. Clinical Endocrinology. 2015.

7. Cardiovascular Manifestations and Complications of Pheochromocytomas and Paragangliomas. — Y-Hassan S, Falhammar H. Journal of Clinical Medicine. 2020.

8. Pheochromocytoma Mimicking Acute Coronary Syndrome: A Case Report. — Cheng Y, Qin L, Chen L. Frontiers in Oncology. 2022.

9. Pheochromocytoma Crisis Rescued by Veno-Arterial Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy. — Nakayama T, Ito K, Inagaki F, et al. The American Surgeon. 2023.

10. Approach to the Management of Gastrointestinal Manifestations in Patients With Phaeochromocytoma and Paraganglioma. — Majumder M, Chiang C, Kong G, et al. Clinical Endocrinology. 2025.

11. Malignant Hypertension:A Systemic Cardiovascular Disease: JACC Review Topic of the Week. — Boulestreau R, Śpiewak M, Januszewicz A, et al. Journal of the American College of Cardiology. 2024.

12. Pathophysiology and Acute Management of Tachyarrhythmias in Pheochromocytoma: JACC Review Topic of the Week. — Nazari MA, Rosenblum JS, Haigney MC, Rosing DR, Pacak K. Journal of the American College of Cardiology. 2020.

13. Neuroendocrine and Adrenal Tumors. — Updated 2026-04-21. National Comprehensive Cancer Network.

14. 2025 AHA/­ACC/­AANP/­AAPA/­ABC/­ACCP/­ACPM/­AGS/­AMA/­ASPC/­NMA/­PCNA/­SGIM Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/­American Heart Association Joint Committee on Clinical Practice Guidelines. — Jones DW, Ferdinand KC, Taler SJ, et al. Journal of the American College of Cardiology. 2025.

15. Treatment of Hypertensive Crisis. — Calhoun DA, Oparil S. The New England Journal of Medicine. 1990.

16. Pheochromocytoma and Paraganglioma. — Neumann HPH, Young WF, Eng C. The New England Journal of Medicine. 2019.

17. Genetics of Pheochromocytoma and Paraganglioma. — Wachtel H, Fishbein L. Current Opinion in Endocrinology, Diabetes, and Obesity. 2021.

18. Pheochromocytoma Manifested as a Surgical Emergency. — Yiannakopoulou E. European Journal of Surgical Oncology : The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2025.

19. Cardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review. — Januszewicz A, Mulatero P, Dobrowolski P, et al. Journal of the American College of Cardiology. 2022.

20. A Rare Initial Presentation of Giant Pheochromocytoma: A Case Report of Acute Pulmonary Embolism Complicated by Catecholamine-Induced Cardiomyopathy. — Zhao L, Zhang Y, Zhou Y, et al. Frontiers in Oncology. 2025.

21. European Association of Nuclear Medicine Practice Guideline/­Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for Radionuclide Imaging of Phaeochromocytoma and Paraganglioma. — Taïeb D, Hicks RJ, Hindié E, et al. European Journal of Nuclear Medicine and Molecular Imaging. 2019.

22. Acute Myocardial Injury Induced by Pheochromocytoma: A Case Report. — Li G, Xu S, Shi S, et al. BMC Cardiovascular Disorders. 2025.

23. Pheochromocytoma/­Paraganglioma-Associated Cardiomyopathy. — Szatko A, Glinicki P, Gietka-Czernel M. Frontiers in Endocrinology. 2023.

24. Pheochromocytoma Is Characterized By Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, And Myocardial Dysfunction. — Ferreira VM, Marcelino M, Piechnik SK, et al. Journal of the American College of Cardiology. 2016.

25. Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter?. — Petrák O, Krátká Z, Holaj R, et al. Hypertension. 2024.

26. Pheochromocytoma Multisystem Crisis Requiring Temporary Mechanical Circulatory Support: A Narrative Review. — Giraud R, Glauser A, Looyens C, et al. Journal of Clinical Medicine. 2025.