Adrenal Catecholamines

Question 1

What stain turns chromaffin cells yellow?

Answer 1

Chromium treatment

Question 2

What are chromaffin cells thought of in terms of pre or post ganglionic nerves?

Answer 2

Think of them as post-ganglionic sympathetic neurons considering their contents

Question 3

What do chromaffin granules contain?

Answer 3

Chromogranin A (tumor marker)
Chromogranin B (tumor marker)
ATP
Neuropeptide Y
Enkephalins
Adrenomedullin

Question 4

How are catecholamines concentrated?

Answer 4

By 4:1 binding with an ATP molecule (proton pumps them in)

Question 5

What is the vesicular proton pump needed for?

Answer 5

Catecholamine concentration in chromaffin granules

Question 6

What is Adrenomedullin?

Answer 6

It is a marker for catecholamine release; increased would mean pheochromocytoma

Question 7

What is the pathway for formation of the catecholamines?

Answer 7

Phenylalanine-> Tyrosine-> Dopa-> Dopamine-> Norepinephrine-> Epinephrine

Question 8

What step does the catecholamine synthesis usually begin?

Answer 8

Tyrosine

Question 9

Rate limiting step in normal catecholamine synthesis?

Answer 9

Tyrosine to Dopa Tyrosine hydroxylase

Question 10

What enzyme is needed for phenylalanine to tyrosine formation?

Answer 10

Phenylalanine hydroxylase

Question 11

What enzyme is needed for tyrosine to dopa formation?

Answer 11

Tyrosine hydroxylase

Question 12

What enzyme is needed for dopa to dopamine formation?

Answer 12

L-Aromatic amino acid decarboxylase

Question 13

What enzyme is needed for dopamine to norepinephrine formation?

Answer 13

Dopamine-Beta-hydroxylase

Question 14

What enzyme is needed for norepinephrine to epinephrine formation?

Answer 14

PNMT

Question 15

What is the rate limiting step in pheochromocytoma patients?

Answer 15

Norepinephrine to epinephrine formation (PNMT)

Question 16

What controls the action of PNMT?

Answer 16

Glucocorticoid stimulation

Question 17

Normal persons epinephrine to norepinephrine ratio?

Answer 17

4:1

Question 18

Pheochromocytoma patient epinephrine to norepinephrine?

Answer 18

1:5

Question 19

Where is the only place that epinephrine is synthesized?

Answer 19

Adrenal medulla

Question 20

What inhibits tyrosine hydroxylase?

Answer 20

Alpha-methyl tyrosine

Question 21

What inhibits vesicular monoamine transport?

Answer 21

Cocaine
Guanethidine
Selective norepinephrine reuptake inhibitors
Tricyclic antidepressants

Question 22

What effect do monoamine oxidase inhibitors have?

Answer 22

Inhibit the breakdown of catecholamines

Question 23

What effect do COMT inhibitors have?

Answer 23

Inhibit breakdown of catecholamines

Question 24

What two enzymes are needed for breakdown of catecholamines?

Answer 24

COMT

MAO

Question 25

What do you use alpha-methyl tyrosine to treat?

Answer 25

Pheochromocytoma inoperable one

Question 26

What are the side effects of alpha-methyl tyrosine?

Answer 26

Cystalluria (renal damage) Sleepiness Parkinson's syndrome (decreased dopamine)

Question 27

What are the two breakdown pathways of norepinephrine?

Answer 27

Norepinephrine to Normetanephrine via COMT Normetanephrine to Vanillylmandelic acid via MAO Norepinephrine to Dihydroxymandelic acid via MAO Dihydroxymandelic acid to Vanillylmandelic acid via COMT

Question 28

What are the two breakdown pathways of epinephrine?

Answer 28

Epinephrine to Metanephrine via COMT Metanephrine to Vanillylmandelic acid via MAO Epinephrine to Dihydroxymandelic acid via MAO Dihydroxymandelic acid to Vanillylmandelic acid via COMT

Question 29

What test has high specificity for Pheochromocytoma?

Answer 29

Plasma Metanephrine levels

Question 30

Why are metanephrine levels tested and not Normetanephrine for pheochromocytoma?

Answer 30

Because only the adrenal medulla forms epinephrine and a pheochromocytoma acts as that; the periphery can increase norepinephrine levels

Question 31

What test has the greatest sensitivity to pheochromocytoma?

Answer 31

24 hour urine measurements of epinephrine, norepinephrine and VMA

Question 32

What is given in imaging studies to locate the pheochromocytoma tumor?

Answer 32

Meta-iodobenzylguanidine

Question 33

How is meta-iodobenzylguanidine uptaken?

Answer 33

Via neuronal uptake

Question 34

What has a higher sensitivity and specificity but is often only used in PET scanners?

Answer 34

F DOPA

Question 35

Where is meta-iodobenzylguanidine uptaken?

Answer 35

Pheochromocytoma | Moderate in liver, salivary glands, urine

Question 36

What is the treatment of symptomatic pheochromocytoma?

Answer 36

Alpha-1-antagonist Prazosin + Beta blocker in preparation for surgery

Question 37

What is the mechanistic treatment of pheochromocytoma?

Answer 37

Alpha-methyl tyrosine or Beta blocker + phenoxybenzamine (non-selective alpha blocker) or surgery