Phaeochromocytoma

• A phaeochromocytoma is a tumour of the adrenal glands that secretes unregulated and excessive amounts of catecholamines:

  • Adrenaline
  • Noradrenaline
  • Dopamine
• Chromaffin cells are predominantly found in the adrenal medulla, but also in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis.
• Up to 40% of phaeochromocytomas may have a hereditary component. Three familial syndromes are strongly associated with these catecholamine-secreting tumours:

  • MEN2
  • Von Hippel-Lindau (VHL) syndrome
  • NF type 1
• Phaeochromocytomas are neuroendocrine tumours arising from chromaffin cells.
• Catecholamines have wide-ranging effects as part of the normal sympathetic nervous system through activation of alpha and beta-adrenergic receptors. These effects include:

  • Alpha-adrenergic: elevated bloods pressure, increased cardiac contractility, increased glucose utilisation (glycogenolysis/gluconeogenesis).
  • Beta-adrenergic: increased heart rate, increased cardiac contractility.
• The major concern is a sudden dramatic release in catecholamines leading to a 'hypertensive' or 'phaeochromocytoma' crisis.

  • Drugs - opiates, beta blockers, cocaine
  • Physical - direct pressure or handling during surgery
  • Anaesthesia - intubation
• Phaeochromocytomas are characterised by a triad of episodic headache, sweating and tachycardia.
• Classically, clinical features of phaeochromocytoma are paroxysmal. However, some patients may have more persistent symptoms, while others are asymptomatic.
• Symptoms:

  • Headache
  • Sweating
  • Tachycardia
  • Palpitations
  • Dyspnoea
  • Weakness
  • Tremor
  • Nausea
• Signs:

  • Hypertension
  • Postural hypotension
  • Weight loss
  • Pallor
  • Arrhythmias
  • Pulmonary oedema
  • Fever
  • Tremor
• Patients may develop severe symptoms relating to a hypertensive crisis, also known as a phaeochromocytoma crisis. If severe, it may lead to circulatory collapse.

  • Hypertension
  • Hyperthermia
  • Confusion
  • End-organ dysfunction (e.g. cardiomyopathy, pulmonary oedema)
  • Hypertension
• Who to test:

  • Classic triad
  • Hyperadrenergic spells  (paroxysmal palpitations, sweating, headache, tremor, pallor)
  • Atypical hypertension (early onset, resistant to treatment)
  • Associated familial syndrome
  • Family history
  • Typical adrenal adenoma on imagine
• Initial tests include:

  • Plasma free metanephrines
  • 24-hour urine catecholamines
• Measuring the serum catecholamine or adrenaline level is unreliable as the levels fluctuate and have a very short half-life of only a minute or so. Metanephrines (a breakdown product of adrenaline) have a longer half-life with more stable levels.
• CT or MRI can be used to look for the tumour.
• The definitive management of a phaeochromocytoma is surgical resection following medical optimisation.
• The most effective method to control blood pressure is combined alpha and beta-adrenergic blockade. Beta-blockers should never be used as single therapy as it can precipitate hypertensive crisis
• Patients are encouraged to have a high sodium diet due to the volume loss with excessive catecholamines and increased risk of orthostatic hypotension with alpha-blockers.
• Complications:

  • Cardiac: cardiomyopathy, cardiac arrhythmias, hypertension
  • Metabolic: Type 2 diabetes mellitus
  • Neurological: stroke, seizure, cerebral haemorrhage (usually from hypertensive crisis)
  • Post-surgical: recurrent disease, adrenal insufficiency (if bilateral resection)
• The alpha-blocker typically used is phenoxybenzamine