Pheochromocytoma Flashcards
Adrenal Medulla v. Symp NS
- adrenal medulla has PMNT and cortisol co-factor to make epi
- *Except organ of Zuckerkandl (sympathetic plexus at aorta bifurcation that has PMNT but usually regresses by end of infancy)
- Adrenal gland releases catecholamines right into blood stream instead of using post-synaptic ganglion
Chromaffin Cells
- From neural crest cells
- 90% in adrenal medulla and 10% in symp/parasympathetic ganglia
Catecholamine Synthesis
- Precursor is tyrosine (diet or conversion from phenylalanine in liver)
- Tyrosine –> L-dopa (rate-limiting step in cytosol by tyrosine hydroxylase)
- L-dopa –> dopamine (aromatic AA decarboxylase also in cytosol)
- Dopamine transfered to vesicles in chromaffin granules –> NE (DBH)
- NE diffuses back into cytoplasm –> epi (requires PMNT and cortisol as co-factor)
What triggers catecholamine release from adrenal?
Hypotension, fever, cold, hypoglycemia, exercise, trauma, bleeding and emotional distress –> symp CNS to release Ach at pre-ganglionic nerve endings –> depolarizes chromaffin cells in adrenal medulla –> inc intracellular Ca++ –> exocytosis of granules w/ catecholamines
Metabolism of Catecholamines (3 enzymes)
1- COMT - converts epi –> metanephrine AND NE –> normetanephrine
- Metanephrine and normetanephrine can be meas in blood and are excreted in urine
2/3- Monoamine Oxidase /Aldehyde Dehydrogenase - further breaks down meta/normetanephrine –> vanillymendelic acid also excreted in urine
Things that can mimic pheo
- angina, MI, HTN w/ MAO inhibitors, abrupt stop in clonidine therapy, acute pulmonary edema, migraine, brain tumor,
- Sympathomimetic drugs - pseudoephedrine, phenylephrine, stimulant, herbal supplements, ephedra (cause false pos labs so hold off then re-test)
Pheo Symptoms (+classic triad)
- Epi - inc HR, hyperglycemia, HTN (can be life-threatening, sustained or paroxysmal), arrhythmias, inc flow to muscles
- Classic Triad - headache, sweating, palpitations
- Others - nausea, vomiting, anxiety, wt loss, chest pain, hyperglycemia, orthostatic hypotension (b/c adapt to vasoconstriction by dec blood volume and down-regulation of normal compensatory symp NS)
When should you screen for pheo?
- Classic triad of headache, sweating, and tachycardia, whether or not they have hypertension
- Severe/resistant hypertension
- Hyperadrenergic spells: self limited episodes of nonexertional palpitations, sweating, headache, tremor, pallor (most patients with spells don’t have pheo)
- Onset of HTN at a young age (<20yrs)
- Family history of pheochromocytoma
- Early trimester hypertension in pregnancy
- Severe pressor responses induced during anesthesia, intubation, surgery, angiography, parturition, or with Beta-blockers (un-opposed alpha from circulating catecholamines from pheo)
- Presence of familial disorder associated with pheo
- Incidentally discovered adrenal adenoma with or without hypertension
- Idiopathic dilated cardiomyopathy
Pheo Dx (screen + confirm)
- Screen w/ metabolites (more reliable)
- Plasma metanphrine and normetanephrine (after rest)
- 24 hr urine collection of metanephrine, normetanephrine AND dopamine
- Clonidine Suppression Test
- Clonidine acts on alpha-2 receptors in brain so when given this should suppress sympathetic physiological NE release
- If adequate suppression … no pheo (elevated due to sympthetic hyper-activity)
- If no suppression … suggests pheo
- Clonidine acts on alpha-2 receptors in brain so when given this should suppress sympathetic physiological NE release
If suspect pheo, where should you image?
look in adrenals, organ of Zuckerkandl, symp plexi (bladder, kidney, heart, mediastinum) and parasympathetic ganglia of head and neck
Tx of non-malignant pheo
- Surgical resection w/ pre-operative volume expansion (Na tablets) to prevent hypotension once tumor is removed AND alpha-blocker (phenoxybenzamine, prazosin) for at least 7 days prior to surgery to control preoperative HTN and antagonize effects of massive catecholamine release during surgery
- Can also use Ca Channel blockers w/ alpha receptor blockers
- Metyrosine - comp inhibitor of tyrosine hydroxylase to dec synthesis; can be used pre-operatively
Tx of malignant pheo w/ mets
- usually not curable but still options
- High doses 131I-MIBG if the metastatic tumor concentrates MIBG and thus delivers high dose local 131I to the tumor
- If not responsive - treat HTN
- Can try chemo or radiation
Pheo v. Paraganglion Tumor
- Pheochromocytoma - derived from adrenal medulla; has PMNT so can make NE or epi (NE more common - less symptomatic); all functional
- Paraganglion - from symp or parasymp chromaffin cells; NE only
- 95% symp are functional but only 5% parasympathetic are functional
