Can anyone help interpret results of a Metypirone test?

[Granny56]

My adrenal function has been sluggish with cortisol levels taking almost one year to return to the "normal" range, albeit the lower end of normal. My endo decided to further evaluate the HPA axis.

Last week, I was given 3000 of Metypirone at midnight to block adrenal function. At 07:30 the following morning, blood was checked for cortisol, ACTH and 11-Deoxy-cortisol.

Results:

ACTH : 398.0 (58.1 pg/ml prior to test) ref range <46.8

Cortisol : 4.0 (8.2 ug/dl prior to test) ref range 3.44-22.45)

Specific ranges

Morning: 07:00-09:00 5.25-22.45

Early evening 15:00-17:00 3.44-16.76

11- Deoxy cortisol 117 (0.18 ng/ml prior to test) ref range <,0.33

I was told by the doctor in hospital, that the Metypirone would block my adrenal function overnight but will have worn off by the morning therefore there should be a spike in cortisol levels noted between 06:00-08:00 to demonstrate that my adrenal glands have recovered and are functioning.

Another doctor in the same hospital contradicted this explaination stating that a low cortisol was expected in the morning because the glands have been suppressed. Now I don't know who to believe.

According to the drug company's SPC, another blood sample should have been drawn at 16:00 to check the cortisol response. It was drawn but it only included electrolytes as my potassium was too low.

I've never had a problem with ACTH, only with cortisol. Can anyone shed more light on these results?

[Ratkinson]

Found this on Wikipedia :Metyrapone can be used in the diagnosis of adrenal insufficiency. Metyrapone 30 mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220 nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothalamo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore, if 11-deoxycortisol levels do not rise and remain less than 7 µg/dl (202 nmol/l) and ACTH rises, then it is highly suggestive of adrenal insufficiency. If neither 11-deoxycortisol nor ACTH rise, it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus.

[Granny56 in reply to Ratkinson]

Thank you, if I understand this correctly this would mean that the doctor stating that my low morning cortisol was as expected, the adrenal cortex remained blocked or suppressed for eight hours, and that the increase in the other two hormones suggest an intact HPA axis.

What I don't understand is why my cortisol level does not rise and fall to within " normal ranges" throughout the day. The pre test morning serum level was as stated above 8.2 , the lower end if normal. This result indicates the highest level attained by my body, which should then fall as the day progresses. I have never had a saliva test to monitor the trajectory throughout the day, I don't think endo will do anymore, she has proved her point (from her perspective). The low cortisol affects my blood pressure dramatically.

Incidently, the dose I should have been given is 2610 mg and not 3000 mg. no snack was offered but I had read the product characteristics before the test therefore, I had to inform the medical staff.

[SilverAvocado in reply to Granny56]

I'm not quite sure what you were saying about the saliva test. Is it that the Endo is satisfied that your adrenals are fine?

Generally the NHS only acknowledged the very extreme forms of adrenal problems. But the 24hr saliva test is intended to pick up more subtle problems, and many people on this website get this test by mail order, and self treat. Adrenals in good working order are necessary to get the full benefit out of thyroid medication, as they contribute to the conversion to the active form.

[Granny56 in reply to SilverAvocado]

For the past year my adrenal function has not been normal. My morning cortisol was as low as 1ug/dl and my blood pressure was dropping below 90 mmhg systolic. Considering the fact that I am normally hypertensive and was on maximum dose BP medications (systolic >200mmhg). Due to adrenal insufficiency, my BP medications were severly reduced but not stopped due to hypertensive heart disease and the need to continue to support the pump action.

Gradually, the cortisol levels increased but even after a short synacthen test, they remained in the lower range of normal. My endo wanted to prove that my HPA was intact after I suggested that there might be an issue. The Metypirone test results imply that no HPA issue exists therefore the issue might lie within the adrenal cortex itself.

When blood is withdrawn to test cortisol, it is usually taken in the morning because it will be at its highest levek. The normal patrern is a downward trend but this can fluctuate especially in periods of stress. A saliva test (taken on at least 5 different occasions) can therefore be more useful to demonstrate the individual pattern of cortisol throught the day rather than a single morning blood test.

I want to optimise my thyroid function and control my labile hypertension, for this to happen I need to be producing cortisol in adequate amounts and be able to have a proper stress response. Mostly, I need to feel well to cope with my complex situation.

I work outside the UK therefore my endo is not NHS.

[Ratkinson]

Hi again

I have secondary addisons due to the removal of my pituitary gland so am not particularly well informed with primary. Every now and then I have a day curve of my cortisol levels done to check I am on the right dose of replacement. I never have my levels checked by saliva testing , always serum, with bloods taken every hour over the course of a day. My results are usually expressed in nmol/l.

Do you have postural hypotension? I use that as an indicator of being too low on my cortisol levels.

If you have not already come across the ADSHG group that will be a good resource for you , they have some very well informed members with primary addisons . Have a look at their forum.

addisons.org.uk/index.php/i...

Some members take a long time to get diagnosed as function can decline over a number of years and it can also be difficult to find a good endocrinologist with experience in this area, so they may be able to point you in the right direction of a more suitable specialist.

Rachel

[Granny56 in reply to Ratkinson]

Thank you Rachel, primary adrenal dysfunction has been excluded and I am happy with this diagnosis. Secondary dysfunction has been confirmed but the cause is not known. The latest test rules out a problem in the higher centres in the brain but doctors don't want to look further.

Yes I suffer from postural hypotension. My morning BP this morning at 07:00 was 100/50 when I got out of bed. At 11:00 I checked again before taking my tablets and it was 148/95. It is so difficult to manage as it fluctuates rapidly to both extremes.

I have started taking spasms in my hands and legs, this had stopped for a while as my cortisol levels increased so I was surprised when they started again.

I will certainly explore the link, many thanks.

[faith63]

i was told to take the metapyrone, at home and go to the lab. My cortisol is very low already and i was too afraid to take the pills at home, in case of adrenal crisis.

[Granny56 in reply to faith63]

I read that this test can be done as an outpatient, however, if you have additional risk factors then you should have it done as an inpatient.

I was an inpatient but there wasn't any monitoring, simply take the tablets and we'll see you in the morning for the blood test. Like you I was afraid as I have experienced adrenal crisis in the past and its not pleasant. I monitored by BP pulse and blood glucose via my own machines until I fell asleep. Everything was stable until the next morning when my BP shot up over 200 systolic 121 diastolic and a few hours later my blood glucose was 208 (11.5 mmols). After that, everything settled down and I was fine. Doctors were not really interested in these spikes, one even said about ny BP " that's not our specialty".