Pheochromocytoma and Paragangliomas Flashcards
What is the rate limiting step of catecholamine synthesis?
Tyrosine -> dopa
What is the pathway from tyrosin to epinephrine? What cofactor are involved?
tyrosin - dopa - dopamine - NE -(PMNT)- epi
Cortisol is the cofactor for PMNT
What two ways are catecholamines removed from circulation?
- Reuptake by sympathetic nerve terminals
2. Metabolism through COMT or MAO
What are the two metabolism pathways for epinephrine?
EPI -COMT-> metanephrinc -MAO-> vanillylmandelic acid
EPI -MAO->dihyroxymandelic acid -COMT->
vanillylmandelic acid
What are the two metabolism pathways for norepinephrine?
NE –COMT-> normetanephrine –MAO> vanillylmandelic acid
NE –MAO-> dihydroxymandelic acid –via COMT-> vanillylmandelic acid
What is the metabolic pathway for dopamine?
Dopamine -> (via COMT and MAO)-> homovanillic acid
sulfate conjugation -> renal excretion
What are the 3 types of Adrenergic receptors? and their
alpha1,2, beta1,2,3, Dopamine receptor1,2
What do a1 receptors mediate?
postsynaptic:
vascular/smooth muscle contraction = increases blood pressure
What do a2 receptors mediate?
presynaptic: inhibit norep release
decrease BP
What do B1 receptors mediate?
cause positive inotropic + chronotropic fx increase: renin release lipolysis bronchodilation vasodilationglycogenolysis increase norepi release
What do B2 receptors mediate?
bronchodilation and vasodilation
What do B3 receptors mediate?
regulates energy expenditure and lipolysis
What do DA1 receptors mediate?
causes vasodilation in vascular beds @:
- cerebral
- renal
- mesenteric
- coronary vasculature
What is the selectivity of EPI and NE on adrenergic receptors?
EPI: slightly more active at A1
EPI+NE: equally active at alpha 2 and beta 1
EPI: MORE ACTIVE AT B2 receptor (this is why you give epi to asthma patients)
What are paraganglia cells?
small organs consisting of mainly neuroendocrine cells
from embryonic neural crest
SECRETE CATECHOLAMINES
What are Paragangliomas?
located in sympathetic paravertebral ganglia of thorax, abdoman, pelvis
usually secrete catecholamines and metanephrines
What is the rule of 10s of pheochromocytomas?
10%: malignant bilateral extra-adrenal calcified in children
What is the age range of highest incidence of pheos?
30-50s
Where are paragangliomas usually found?
para-aortic sympathetic chain
origin of the inferior mesenteric artery
wall of urinary bladder
sympathetic chain in the neck or mediastinum
What two syndromes are related to bilateral pheos?
MEN
Von Hippel-Lindau
What syndrome is related to GISTs and paragangliomas (sympathetic or parasympathetic)
Carney-Stratakis dyad
What syndrome is related to paragangliomas that are located in the skull base and neck, thorax, abdomen, pelvis
Familial paraganglioma (5 PGL syndromes)
What is the difference between MEN 2A and MEN 2B? What traits do they both share?
BOTH: medullary thyroid cancer, pheo/paraganglioma
MEN2A: primary parathyroid hyperplasia
MEN2B: NO hyperPTH
What is the genetic cause of MEN?
Chromosome 10q - RET mutation
