Physiology · Year 1 · from Physiology

Case 2: Pheochromocytoma - Catecholamine Excess

Clinical Image

Source: Wikimedia Commons - Pheochromocytoma Scan - CC BY-SA 3.0

Patient Presentation

A 42-year-old female presents to her primary care physician with episodes of severe headache, palpitations, and profuse sweating occurring several times per week for the past 6 months. Episodes last 15-30 minutes and are often triggered by physical exertion or emotional stress. Between episodes, she feels relatively well but notes persistent anxiety. During one episode in the office, her blood pressure was measured at 220/130 mmHg, which normalized to 145/92 between episodes. She has no significant past medical history but mentions her father had thyroid cancer.

Demographics

  • Age: 42 years
  • Sex: Female
  • Family history: Father with thyroid cancer (raises suspicion for MEN2)

Chief Complaint

Episodic severe headaches, palpitations, diaphoresis, and paroxysmal hypertension

Physical Examination

During Episode:

  • Vital signs: BP 218/128, HR 128, RR 22, diaphoretic, tremulous
  • General: Anxious, pale, diaphoretic
  • Cardiovascular: Tachycardic, regular rhythm

Between Episodes:

  • Vital signs: BP 148/94, HR 82
  • Thyroid: No palpable nodules
  • Skin: Cafe-au-lait spots noted (concerning for neurofibromatosis, associated with pheochromocytoma)

Workup

  • 24-hour urine catecholamines and metanephrines: Markedly elevated (norepinephrine 1,250 mcg/24h [normal <80], normetanephrine 4,500 mcg/24h [normal <900])
  • Plasma free metanephrines: Elevated
  • CT abdomen: 4.5 cm right adrenal mass with heterogeneous enhancement, Hounsfield units >10
  • MIBG (I-123 metaiodobenzylguanidine) scan: Uptake in right adrenal mass, no extra-adrenal disease
  • Genetic testing: RET proto-oncogene mutation identified (MEN2A)
  • Screening: Calcitonin elevated (medullary thyroid cancer); calcium/PTH normal
  • Echocardiogram: Mild LVH, normal EF (catecholamine-induced cardiomyopathy screening)

Diagnosis

Pheochromocytoma as part of Multiple Endocrine Neoplasia Type 2A (MEN2A)

Treatment

  1. Preoperative alpha-blockade first: Phenoxybenzamine 10 mg BID, titrate to control BP (target BP <130/80 seated, >90 standing)
  2. Then beta-blockade (after adequate alpha-blockade): Metoprolol or propranolol for tachycardia
  3. High-salt diet and fluids to expand contracted intravascular volume
  4. Surgical resection: Laparoscopic adrenalectomy after 10-14 days of medical preparation
  5. Intraoperative management: Arterial line, prepared for hypertensive crisis and hypotension post-tumor removal
  6. MEN2A management: Prophylactic thyroidectomy for medullary thyroid cancer (high RET mutation risk)
  7. Genetic counseling and screening of first-degree relatives
  8. Lifelong surveillance for recurrence and contralateral pheochromocytoma

Physiological Principles Demonstrated

  • Adrenal medulla as modified ganglion: Chromaffin cells are developmentally related to sympathetic postganglionic neurons but release catecholamines directly into the bloodstream (epinephrine 80%, norepinephrine 20%).
  • Catecholamine synthesis: Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine. Pheochromocytomas may secrete predominantly norepinephrine (as in this case) or epinephrine.
  • Adrenergic receptor effects:
  • Alpha-1: Vasoconstriction → hypertension, pallor
  • Beta-1: Increased HR and contractility → palpitations, tachycardia
  • Beta-2: Sweating (sympathetic cholinergic to most sweat glands, but adrenergic effects occur with circulating epinephrine)
  • Why alpha-blockade first: Beta-blockers alone would block beta-2 vasodilation (skeletal muscle), leaving alpha-1 vasoconstriction unopposed → paradoxical worsening of hypertension. Alpha-blockade must precede beta-blockade.
  • Volume contraction: Chronic catecholamine excess causes vasoconstriction and pressure natriuresis, contracting plasma volume. After tumor removal, loss of vasoconstriction → profound hypotension unless volume is repleted preoperatively.
  • Episodic symptoms: Tumor releases catecholamines intermittently, often triggered by tumor manipulation, exercise, anesthesia, or certain foods/medications.

All cases for this lecture as Markdown