Adrenal Medulla

Question 1

Catecholamine production and metabolism

Answer 1

• catecholamines are synthesized from tyrosine in postganglionic sympathetic nerves (norepinephrine) and chromaffin cells of adrenal medulla (epinephrine)
• broken down into metanephrines and other metabolites (VMA, HVA) and excreted in urine

Question 2

ABCs of Adrenaline

Answer 2

Adrenaline activates

Beta-receptors, increasing

Cyclic AMP

Question 3

Pheochromocytoma definition

Answer 3

rare catecholamine secreting tumour derived from chromaffin cells of the sympathetic system

Question 4

Pheochromocytoma epidemiology

Answer 4

• most commonly a single tumour of adrenal medulla

* rare cause of HTN (<0.2% of all hypertensives)

Question 5

Pheochromocytoma etiology and pathophysiology

Answer 5

• most cases sporadic (80%)
• familial: associated with multiple endocrine neoplasia II (MEN IIA and IIB (50% penetrance; i.e. 50% of people with the mutation get pheochromocytoma), von Hippel-Lindau (10-20% penetrance), paraganglioma (20% penetrance), or neurofibromatosis type 1 (0.1-57% penetrance)
• tumours, via unknown mechanism, able to synthesize and release excessive catecholamines

Question 6

Pheochromocytoma clinical features

Answer 6

• 50% suffer from paroxysmal HTN; the rest have sustained HTN
• classic triad (not found in most patients): episodic “pounding” headache, palpitations/tachycardia, diaphoresis
• other symptoms: tremor, anxiety, chest or abdominal pain, N/V, visual blurring, weight loss, polyuria, polydipsia
• other signs: orthostatic hypotension, papilledema, hyperglycemia, dilated cardiomyopathy
• symptoms may be triggered by stress, exertion anesthesia, abdominal pressure, certain foods (especially tyramine containing foods)

Question 7

Pheochromocytoma investigations

Answer 7

• urine catecholamines
■ increased catecholamine metabolites (metanephrines) and free catecholamines
■ plasma metanephrines if available (most sensitive)
◆ cut-off values will depend on assay used

• CT abdomen
■ if negative, whole body CT and meta-iodo-benzoguanidine (MIBG) scintigraphy, Octreoscan, or MRI

Question 8

Pheochromocytoma treatment

Answer 8

• surgical removal of tumour (curative) with careful pre- and post-operative ICU monitoring

• adequate pre-operative preparation
■ α-blockade for BP control: doxazosin or calcium channel blockers (10-21 d pre-operative), IV phentolamine (perioperative, if required)
■ β-blockade for HR control once α blocked for a few days
■ metyrosine (catecholamine synthesis inhibitor) + phenoxybenzamine or prazosin
■ volume restoration with vigorous salt-loading and fluids

• rescreen urine 1-3 mo post-operatively
• screen urine in first degree relatives; genetic testing in patients <50 yr old