Testing and Diagnosis of Adrenal Insufficiency

Algorithm for the diagnosis of adrenal insufficiency (AI).  by Cleveland Clinic.

If you or your Dr suspect you have Adrenal insufficiency then testing should be carried out as quickly as possible, and unless in hospital in a crisis situation, testing should happen before 9 am.

If you are being tested for suspected  adrenal insufficiency, there should be a three-step process.
1.  Diagnose the condition.
2. Find out if you are Primary (the Adrenal Glands are at fault) or Secondary (the Pituitary Gland is at fault) or in rare circumstances Tertiary (the hypothalamus is at fault).
3. Find out what is causing your Adrenal Insufficiency.
Check here to see the more common causes of PAI and SAI

When being tested some things to be aware of.

Medications that can affect the results of the cortisol and/or ACTH tests:
Amphetamines (including Ritalin, Adderall, dexamphetamine, doxepin, Dexedrine, Concerta, metadata CD, insulin, levodopa, Sinemet, metoclopramide, RU 486, megestrol acetate, birth control pills, estrogen, amphetamines, or other corticosteroids such as dexamethasone, prednisone, hydrocortisone, prednisolone, or methylprednisolone.

Medical conditions and situations can also result in altered test results:
Liver disease, kidney disease, depression, hyperthyroidism, obesity, pregnancy, recent surgery, illness, injury, whole-body infection (sepsis), low BG (hypoglycemia) eating, drinking, exercising before the test, or having a radioactive scan within one week of the test.

The ACTH stimulation test.

As you can see from the figure above from the Cleveland Clinic, you need an 8-9am blood plasma cortisol sample to start, this needs to occur with no recent use of steroids whether topical, inhaled or injected.
If the value is lower than 100nmol/L, then a diagnosis of adrenal insufficiency should be immediately confirmed with an URGENT appointment with an Endocrinologist.

If the results for the 9am cortisol is between 100-250nmol/L then your Dr will possibly want to discuss other reasons for this level.  It needs further investigation with a second morning Cortisol test at the very least.  Don’t be brushed off with “it’s fine”.

If the value is between 250-400nmol/L and your Dr says it is fine, talk to them about what was happening on the day of the test. If you day was calm, and nothing out of the norm, you should not be that low.  If it was a bit more hectic than normal such as rushing around getting upset or angry kids out the door to school or you drove yourself to the lab in peak hour traffic where you normally take the train, this may have an impact on your levels.   Your GP should, depending on other signs and symptoms, either want to rerun the test before giving you a referral, or they may just write a referral, but not mark it urgent.  Another thing to consider is your sleep patterns.  If you normally wake up and head to work at 4 am, then your normal highest level will be earlier in the day (around 6am).  This also needs to be factored into the assessment.

If you are in hospital in an adrenal crisis at the time of diagnosis, it will be done bedside.

In New Zealand, to get a confirmed diagnosis of Adrenal Insufficiency you will need an appointment with an Endocrinologist.  To confirm the diagnosis they will give you an ACTH stimulation Test.   In New Zealand this can be done either in the Endocrinologists rooms at your Local Hospital or in an Endocrine Unit if they have one.  If you are living in a more rural area, you may need an appointment at a Tertiary Hospital.

You will arrive at the hospital that is doing the test.  You will have some blood drawn, either by having a catheter (needle with a valve) inserted in your arm, or by routine blood test.  This blood draw should include both a base level of Cortisol, and a test for ACTH.  It is this information which will help confirm Primary or Secondary AI.

Once these bloods are drawn (and ask what blood tests they are doing as it should be 2 vials of blood at least), you will either be given an IV (In the Vein) or IM (In the Muscle) injection of synthetic ACTH.

You will then either have 1 or 2 more vials of blood drawn.  If your Endocrinologist is reasonably certain you have Primary AI then they may only draw one lot of blood.  If they are unsure, they should draw 2, one at 30 minutes after the synthetic ACTH injection, and one at 60 minutes after.

If your adrenal glands are not working properly, when you get your test results back you will see that the level of cortisol didn’t change much from the base level taken before the injection.

Primary or Secondary/Tertiary?

Irrespective of what your baseline cortisol value is, a healthy who does not have AI should reach a level of  at least 500nmol/L by the 30min mark.

If your Serum Cortisol does not reach this mark by 30 minutes, or even 60 minutes, then you will likely get a diagnosis of Primary Adrenal Insufficiency

If your serum cortisol achieves this level, but your baseline cortisol was suboptimal (low enough that they sent you for testing) then, ONLY primary Adrenal Insufficiency is ruled out.

You may still have secondary tertiary adrenal in sufficiency.  This is when the baseline ACTH blood level is helpful.

Primary AI = LOW Cortisol, LOW Simulation Result, HIGH (above range) ACTH
Secondary AI = LOW Cortisol, NORMAL or Blunted Stimulation Result, LOW ACTH
Tertiary AI = LOW Cortisol, NORMAL Stimulation Result, LOW ACTH

If there is a suspicion of Secondary AI due to ACTH suppression from other medications, then you may stimulate, but with a blunted result because damage is already occurring to the adrenal glands.