Pheochromocytoma

Question 1

Definition + rule of 10s

Answer 1

Catecholamine-secreting tumours (release NAd & adrenaline) of chromaffin cells in adrenal medulla.
- Chromaffin cells are neuroendocrine cells (in response to ACh release from preganglionic sympathetic neurones, they release catcholamines NAd & adrenaline) thus pheochromocytomas = neuroendocrine tumours
Rule of 10s:
- 10% of tumours of chromaffin cells are extradrenal (called paragangliomas)- most commonly at the bifurcation of the abdominal aorta
- 10% are bilateral & 10% are malignant & 10% are associated with MEN type 2a & 2b

Question 2

Causes & associations

Answer 2

Most arise sporadically.
10% are associated with :
- Multiple Endocrine neoplasia type 2a & type 2b (due to mutations in RET proto-ocogene –> forms RET oncogene which causes thyroid cancer)

• Neurofibromatosis 1 (benign tumours grow along neurones)
• von Hippel-Lindau disease ( benign & malignant tumours & cysts grow throughout body e.g. renal cellcarcinomas,hemiangioblastomas- slow-growing tumours of CNS)

Question 3

Pathway for catecholamine synthesis?

Answer 3

Tyrosine -> L-dopa-> Dopamine-> Noradrenaline -> Adrenaline

Question 4

Pathophysiology

Answer 4

Tumours of chromaffin cells secreting excess catcecholamines- noradrenaline & adrenaline:
- bind to alpha-1 receptors on VSM -> vasocontriction -> increased TPR -> increases BP
- bind to beta-1 receptors in kidneys & stimulate renin release -> increased plasma volume
- bind to beta-1 receptors in heart & stimulate +ve inotorpy & +ve chronotropy -> increased CO-> increased BP
Resulting in refractory hypertension (not controlled with 3 or more drugs)& tachycardia
- Catecholamine release can be continous or random (induced by stress, food like chocolate & cheese) resulting in episodic presentation of Sx

Question 5

Signs & symptoms

Answer 5

Signs:
- refractory hypertension
- tachycardia
Symptoms
- episodic headaches
- sweating
- anxiety
- nausea
- palpitations
- feeling of impending doom
- Catecholamine release can be continual or pulsatile, worsened by stress & foods like cheese & chocolate

Question 6

Investigations

Answer 6

1st line:
- 24 hr plasma free metanephrines -high , diagnostic
(metanephrines are a breakdown product of adrenaline with longer 1/2 life, plasma catecholamines are unreliable due to short 1/2 life)
- 24 hr urinary metanephrines- high
- CT abdomen/pelvis- to locate adrenal tumour or extra-adrenal tumour of chromaffin cells (most commonly AAA bifurcation)

Question 7

Treatment

Answer 7

Pre-operative anti-hypertensives to decrease bleeding during surgery:
1st line = alpha blocker - phenoxybenzamine
2nd line = cardioselective beta blocker e.g. Atenolol, Metoprolol, Bisoprolol (to reduce tachycardia & prevent tachyarrythmias)
- Giving beta blocker before alpha blocker will cause unopposed stimulation of alpha-1 adrenergic receptors & reactive vasoconstriction leading to hypertensive crisis

Definitive treatment = surgical excision of tumour via laparoscopic adrenalectomy

Question 8

Complications + how to treat this?

Answer 8

• Hypertensive crisis- BP > 180/20 mmHg.
  Give phentolamine (alpha blocker)
  Causes end-organ damage: retinal haemorrhages & hypertensive retinopathy, ischaemic or haemorrhagic stroke, renal failure, congestive heart failure or MI