[hana]

how to interprete the results and when it is used.
in your own words please

 

[dr z]

metyrapone

Metyrapone does not belong to any special class of drugs. It's a very specific drug that has very specific drug action.
MOA
It block cortisol synthesis by blocking 11 beta hydroxylase.
USE
It's used in the diagnosis of adrenal insufficiency.
give the patient Metyrapone at night after you measure ACTH level and 11 deoxycortisol.
INTERPRETATION OF RESULTS
If the patient is having an intact ACTH response to (lowered cortisol) then the next morning you should see increased levels of ACTH and 11 deoxycortisol as the patient has increase his ACTH level but it could not make cortisol as the 11 hydroxylase enzyme is being blocked by metyrapone.
HOPE THIS HELPS.

 

[hana]

@ dr.z;
so if patient has increased ACTH and 11-deoxycortisol after metyrapone administration ,where in HPA axis is teh problem?

 

[dr z]

Metyrapone acts on Blocking 11-beta hydroxylase and this enzyme is present in zona fasciculata.
after giving metyrapone
outcome 1:-
increase ACTH
increase deoxycortisol
decrease cortisol
interpretation Primary Adrenal insufficiency (adrenal cause) HPO axis has no problem

outcome 2:-
decrease ACTH
decrease deoxycortisol
decrease cortisol
interpretation Secondary Adrenal insufficiency( decrease Pitutary ACTH) HPO axis has problem

this is my understanding plz correct me if i m wrong thanks

 

[hana]

1- why do not we just simply measure the ACTH level in patient with adrenal insufficiency to figure out if it is adrenal problem or pitutaory? why all these playings? why using metyrapone then measuring ACTH AND 11DOC?

2-my other confusion is here;
we gave metyrapone,and ACTH is increased ,if 11doc also is increased then we can say pitutary is fine and adrenal has problem right?(i hope atleast i can understand english HOW 11-DOC CAN INCREASE WHEN ADRENAL IS NOT WORKING AT FIRST PLACE? maybe i need to change my understanding of adrenal insufficiency

3- by increasing ACTH after metyrapone-in case of nl pitutary- you mean MORE elevation right? cause ACTH should already be high in adrenal insuficinecy even before using metyrapone:scared:

 

[dr z]

stimulation test

According to kaplan Metyrapone is a Stimulation test, (just like Insulin induced hypoglycemia)
lets start from begining how v will diagnose adrenal insufficiency
1- RAPID ACTH STIMULATION TEST
(page 277 of kaplan green physiobook)
outcome
a- increase cortisol------->Normal
b- no change in cortisol------->Hypocortisolism
(primary/secondary, v have to investigate further)

2- METYRAPONE TESTING / INSULIN INDUCED HYPOGLYCEMIA
outcome
a-MORE increase ACTH, increase deoxycortisol, decrease cortisol{PRIMARY}
b-decrease ACTH, decrease deoxycortisol, decrease cortisol{SECONDARY

3-DEFINATIVE TEST ACTH (PAGE 280 KAPLAN physio)
outcome
a-increase ----->PRIMARY
b-decrease----->SECONDARY

how deoxy still increase as v r overstimulating it by metyrapone(this means that some reseve r still there which come out by metyrapone
now ur question y not ACTH from start , that is something i m missing too, lets c someone else can help us out
and thanks for putting conceptual questions, u make me think deep:happy:

 

[struggle]

according to my understanding as metapyrone blocks 11 Beta hydroxylase so all the products before this blockage will increase,,thats why deoxycortisol will increase in primary problem.
correct me if m wrong.

 

[Mondoshawan]

I think that part of the confusion here is that metyrapone can be used in the diagnosis of Cushing's syndrome as well as adrenal insufficiency.

 

[hana]

according to my understanding as metapyrone blocks 11 Beta hydroxylase so all the products before this blockage will increase,,thats why deoxycortisol will increase in primary problem.
correct me if m wrong.

the thing is that adrenal deficency does not mean only problem with cortisol synthesis and only problem at last step of synthesis which is 11doc conversion to cortisol.
unless this is just the definition of adrenal insufficency : adrenal has problem with" last" step of "cortisol" formation, then we can be sure 11DOC and other things before cortisol elevate by inhibiting the 11 hydroxylase .this is my understanding still open to any idea

 

[hana]

I think that part of the confusion here is that metyrapone can be used in the diagnosis of Cushing's syndrome as well as adrenal insufficiency.

oh no .i know what you are talking about ,but this issue that we are disscusing now is about usage of metyrapone for adrenal deficiency..ets lets get on a conclusion on this one then discusse the other hopefuly this tread solves all metyrapone problems here forever!!

btw this might help you (did not quite help me tho)
http://www.prep4usmle.com/forum/thread/45342/

 

[hana]

@ dr.z;
"....and thanks for putting conceptual questions, u make me think deep"

hana is happy to here that .but really thank you for considering replying and trying to help.i wish you the best score(s).

so what is clear is ;

first,we do not know why we do not measure ACTH FROM BEGINNING,we just do not !

second,if after metyrapon;ACTH IS UPPER,THEN PITUTARY IS GOOD.AND IF ACTH is not chnage(i rather say not changed than decreased cause i do not see any reason for it,it should still be up ),then problem is afrenal.

I HAVE THIS LACK OF CONFIDENC PLUS OBSSESIVE-COMPULSIVE TRAIT! AND NEED TO CHECK EVERYTHING IN DETAILS TO MAKE SURE I GET THEM RIGHT.I THINK I AM NEVER SURE!! THIS IS NOT GOOD FOR THIS EXAM SPECIALLY.

 

[Mondoshawan]

We do measure ACTH from the beginning, as well as CRH, DHEA, renin, aldosterone, and electrolytes. Then the ACTH stimulation test (cosyntropin test), etc. As you mentioned, there are more aspects to the system than ACTH and cortisol.

I mention using metyrapone for Cushing's Dx because I see that some of what people have written are directions for interpreting that test rather than for adrenal insufficiency.

As far as adrenal insufficiency:

• high ACTH and low 11DOC after metyrapone - indicates primary adrenal insufficiency.
• low ACTH and low 11DOC - indicates secondary or tertiary adrenal insufficiency
• 11DOC at baseline (normal) - control; you did not administer sufficient metyrapone to block 11β-hydroxylase activity

I'm pretty sure that's all we can know about adrenal insufficiency from this test.