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ACTH reference ranges at differing times of day?
Hey, folks! I've been looking for a chart or some sort of list of ACTH ranges that show the daily variation in the blood. So far I've only found low to high ranges, like 9-52 pg/mL. and some say 10-60.
Quest Diagnostics did my ACTH level and my daughters. They listed hers at a morning draw as 7, but female ranges from 5-27 pg/mL. Males are listed at 7-50 pg/mL.
They say "There is a diurnal variation"....but then they don't say what time of day to expect it to be a the highest.
I read elsewhere that the levels pretty much follow cortisol levels, high in the morning and decreasing throughout the day until it's lowest at night. Makes sense.
Then shouldn't the reference range indicate that? If her ACTH barely makes the bottom rung of the reference range ladder, doesn't that hint (pretty loudly!) that it probbly goes lower after that, so she could be experiencing insufficient ACTH to make cortisol the rest of the day?
Is I missing something here?
I'm assuming that they don't have enough data to draw good charts for this. Or maybe it fluctuates too wildly to be predictable.
Or,.....maybe....they just ain't that interested in this and don't wanna bother!!!
Nah, that can't be it! ;)
Anyone have a more clear listing of time of day as it relates to ACTH?
FWIW, A good doctor will take the diurnal variation into account, I'm sure. But they're usually so busy they hardly have time to pay attention to any test score that doesn't have a red flag on it, even if it should...
Quest Diagnostics did my ACTH level and my daughters. They listed hers at a morning draw as 7, but female ranges from 5-27 pg/mL. Males are listed at 7-50 pg/mL.
They say "There is a diurnal variation"....but then they don't say what time of day to expect it to be a the highest.
I read elsewhere that the levels pretty much follow cortisol levels, high in the morning and decreasing throughout the day until it's lowest at night. Makes sense.
Then shouldn't the reference range indicate that? If her ACTH barely makes the bottom rung of the reference range ladder, doesn't that hint (pretty loudly!) that it probbly goes lower after that, so she could be experiencing insufficient ACTH to make cortisol the rest of the day?
Is I missing something here?
I'm assuming that they don't have enough data to draw good charts for this. Or maybe it fluctuates too wildly to be predictable.
Or,.....maybe....they just ain't that interested in this and don't wanna bother!!!
Nah, that can't be it! ;)
Anyone have a more clear listing of time of day as it relates to ACTH?
FWIW, A good doctor will take the diurnal variation into account, I'm sure. But they're usually so busy they hardly have time to pay attention to any test score that doesn't have a red flag on it, even if it should...
ACTH has a pulsatile release, meaning most of the time its sits at or around 0. Hence the wide reference range. There is a diurnal variation too, and you're more likely to catch a peak with a morning blood test. However, the normal pulsatility means that a low value is nothing to worry about regardless of when it is taken.
You could check it frequently to look for these spikes, but the short half life means you'd need to sample every minute.
For this reason there is absolutely no value in measuring ACTH, unless you have a condition which means it should be CONSTANTLY high. For example, if you have already been diagnosed with Addison's disease, the pituitary gland should 'sense' the low cortisol levels and try to compensate by keeping the ACTH constantly high. Anything other than this means the pituitary is at fault.
But outwith this context, a 'low' ACTH is meaningless.
You could check it frequently to look for these spikes, but the short half life means you'd need to sample every minute.
For this reason there is absolutely no value in measuring ACTH, unless you have a condition which means it should be CONSTANTLY high. For example, if you have already been diagnosed with Addison's disease, the pituitary gland should 'sense' the low cortisol levels and try to compensate by keeping the ACTH constantly high. Anything other than this means the pituitary is at fault.
But outwith this context, a 'low' ACTH is meaningless.
Ice should help, but it does not.
I found this study:
"Preanalytical factors can affect reliability of hormone assay results. Adrenocorticotropic hormone (ACTH) in blood is considered highly unstable because of proteolytic degradation (1)(2)(3)(4), so storage of blood samples on ice until analysis is recommended. In clinical practice, however, this procedure may present logistical problems because most samples for ACTH measurement must be shipped from the place of sample collection to the laboratory. Therefore, we studied the impact of time and temperature before plasma separation and analysis on the results of ACTH assays.
...
Although the mean decay in measured ACTH concentration after storage for 24 h at room temperature without centrifugation was only 10% [mean (SD), 9% (11%)], the decrease was >20% in samples from 3 healthy volunteers and was not prevented by storage at 4 °C. No relevant change occurred in any of the samples during the first 4 h, however. For clinical practice we therefore recommend that centrifugation and separation of plasma supernatant be performed within 4 h of sample collection. Cooling of samples seems to be much less effective. Thus, the preanalytical procedure can be simplified without risking clinically relevant changes in measured hormone concentrations."
http://www.clinchem.org/cgi/content/full/53/2/358
However, in real life, I know that ACTH degrades in 6-11 minutes once drawn. I have had this test done for over 15 years - and any test done where it has not been spun immediately, my results have been low or normal. And now, when I have an ACTH secreting tumor pumping out lots of ACTH, if they do not spin it right away, I can see my results fall 800 to 1000pg/ml just on handling. I should be only going up based on skin color and symptoms and now that I have a lab working on the results, I have reached almost 4000, but my previous test to that was *degraded, no result* and before that, 2800. I had a doctor tell me how to get the test done as well. But when they take the test in the office, they spin ASAP. In labs where they drew the sample and put it in the freezer, my sample came out low.
Why don't you get your tests done both ways and see if you see a change?
I found this study:
"Preanalytical factors can affect reliability of hormone assay results. Adrenocorticotropic hormone (ACTH) in blood is considered highly unstable because of proteolytic degradation (1)(2)(3)(4), so storage of blood samples on ice until analysis is recommended. In clinical practice, however, this procedure may present logistical problems because most samples for ACTH measurement must be shipped from the place of sample collection to the laboratory. Therefore, we studied the impact of time and temperature before plasma separation and analysis on the results of ACTH assays.
...
Although the mean decay in measured ACTH concentration after storage for 24 h at room temperature without centrifugation was only 10% [mean (SD), 9% (11%)], the decrease was >20% in samples from 3 healthy volunteers and was not prevented by storage at 4 °C. No relevant change occurred in any of the samples during the first 4 h, however. For clinical practice we therefore recommend that centrifugation and separation of plasma supernatant be performed within 4 h of sample collection. Cooling of samples seems to be much less effective. Thus, the preanalytical procedure can be simplified without risking clinically relevant changes in measured hormone concentrations."
http://www.clinchem.org/cgi/content/full/53/2/358
However, in real life, I know that ACTH degrades in 6-11 minutes once drawn. I have had this test done for over 15 years - and any test done where it has not been spun immediately, my results have been low or normal. And now, when I have an ACTH secreting tumor pumping out lots of ACTH, if they do not spin it right away, I can see my results fall 800 to 1000pg/ml just on handling. I should be only going up based on skin color and symptoms and now that I have a lab working on the results, I have reached almost 4000, but my previous test to that was *degraded, no result* and before that, 2800. I had a doctor tell me how to get the test done as well. But when they take the test in the office, they spin ASAP. In labs where they drew the sample and put it in the freezer, my sample came out low.
Why don't you get your tests done both ways and see if you see a change?
I spoke to my doctor about the ACTH test, and she said that as long as the test tube is put on ice, the tube can be centrifuged up to 1 hour later (clearly, we all want to shoot for immediately, but at the lab where I get my blood drawn, that's never gonna happen). So just make sure that they pack the tube in ice. This makes sense, as ACTH is a polypeptide, and the ice alone would slow the degradation.
Ah then you need to go to Esoterix - where the range I think stops at 34!
I hope you can get a doc to listen.
I hope you can get a doc to listen.
Thank you for the info!!
I've seen ranges from some labs say 9-52, others say 10-60 and a few variants of that. By those ranges, she's low. But by Quest, she's fine.
Semi-Sarcastic Solution: You see how you can feel better, folks?? Just go to a different lab with a wider reference range and you'll be in the 'normal' range! Its' that simple!
;)
We've got an appointment next week; gonna suggest to the doc that maybe, just maybe, her pituitary is not doing it's job all that well and he should take a closer look at that.
I've seen ranges from some labs say 9-52, others say 10-60 and a few variants of that. By those ranges, she's low. But by Quest, she's fine.
Semi-Sarcastic Solution: You see how you can feel better, folks?? Just go to a different lab with a wider reference range and you'll be in the 'normal' range! Its' that simple!
;)
We've got an appointment next week; gonna suggest to the doc that maybe, just maybe, her pituitary is not doing it's job all that well and he should take a closer look at that.
There is no range for ACTH at different times of day. I have never even seen the male/female range! And every lab differs.
My doctors therefore insist it is taken at 8am, fasting for 12 hours (ack!) off medications, to get the best results, and consistent results. 8am should be the highest as that is when cortisol is the highest.
If her ACTH is that low... I would say it is lab handling. ACTH is a very very fussy test - it has to go from the vein straight to a centrifuge - absent that, the sample degrades in minutes. If the tech does not use a chilled tube and then pops the sample in the bin, your test will be much lower than it should be.
I argue with the techs all the time - some times my samples came back degraded so the test could not be run! That tech assured me she was professional and knew how to run the test. Bull ptuooty. I even bring ice in a baggy sometimes! My ACTH is in the thousands and my results would fall 800 or more points by lousy handling - that is more than the range! Then I am judged by the lousy test. It ticks me off...
Make sure you are in there, and get a good test done - or go to another location, or lab - speak to the lab supervisor. I used to make a huge fuss. They do the test rarely, and do it badly. I kept going to new locations and other labs.
BTW, the diurnal variation makes 8am highest, and it falls throughout the day, that is why cortisol ranges are lower throughout the day.
My doctors therefore insist it is taken at 8am, fasting for 12 hours (ack!) off medications, to get the best results, and consistent results. 8am should be the highest as that is when cortisol is the highest.
If her ACTH is that low... I would say it is lab handling. ACTH is a very very fussy test - it has to go from the vein straight to a centrifuge - absent that, the sample degrades in minutes. If the tech does not use a chilled tube and then pops the sample in the bin, your test will be much lower than it should be.
I argue with the techs all the time - some times my samples came back degraded so the test could not be run! That tech assured me she was professional and knew how to run the test. Bull ptuooty. I even bring ice in a baggy sometimes! My ACTH is in the thousands and my results would fall 800 or more points by lousy handling - that is more than the range! Then I am judged by the lousy test. It ticks me off...
Make sure you are in there, and get a good test done - or go to another location, or lab - speak to the lab supervisor. I used to make a huge fuss. They do the test rarely, and do it badly. I kept going to new locations and other labs.
BTW, the diurnal variation makes 8am highest, and it falls throughout the day, that is why cortisol ranges are lower throughout the day.
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