• CT (computer tomography) is the imaging study of choice and helps identify adrenal haemorrhage (bleeding), calcifications (boney overgrowth which may suggest TB), or infiltrative disease.
• MRI (magnetic resonance imaging) is not as useful as CT.
• Abdominal radiographs may reveal bilateral adrenal calcifications, which suggest a history of bilateral adrenal haemorrhage, TB or Wolman disease.
• Ultrasound is a poor imaging modality for investigation of the adrenal glands.
• Iodocholesterol scanning is not particularly useful.(Iodocholesterol is an experimental radioactive chemical that, when injected into the vein, is picked up in the adrenal glands and permits visualization with gamma imaging devices.)

Procedures:

• CT-guided fine-needle aspiration sometimes helps establish the aetiology (cause or origin)
  of infiltrative adrenal diseases.

Other tests:

• Electrocardiograph (ECG): Elevated peaked T waves may indicate hyperkalaemia (high potassium).
• 24-hour urinary cortisol: Use only in non-emergency situations.

"How will these tests be done?"

SYNACTHEN TEST (ACTH STIMULATION TEST)

• "What is a short Synacthen test?"
  • It is a test to check the amount of cortisol in your body and to determine how well your body can produce cortisol.
• "What is cortisol?"
  • Cortisol is one of the essential steroid hormones to keep you healthy.You can be unwell if this hormone is too low or too high.
• "What do I need to do before the test?"
  • It will be better to have the test in the morning. You may be requested to remain laying down during the test. You should not have the test if you have significant asthma.
• "How will the test be performed?"
  • You may be asked to lie flat and/or quiet with no external stress for the duration of the test.
  • An initial blood sample will be taken to check the baseline level of cortisol.
  • You will then be given an injection of ACTH (AdrenoCorticoTropic Hormone) to stimulate your own body's production of cortisol.
  • A blood sample will be taken at 30 minutes, and sometimes at 60 minutes, after the stimulation to measure the cortisol level.

The results will reflect how much cortisol you have and how well your body can respond to the stimulation.

This test is not advisable for children, for those with significant heart disease or for those who have epilepsy or have had seizures previously.

Note:

In emergency situations, treatment of presumed adrenal insufficiency should not be delayed in order to await diagnostic testing. Treatment with dexamethasone allows ACTH stimulation testing without affecting or interfering with the measurement of serum cortisol levels.

INSULIN STRESS TEST

• What is the insulin stress test?
  • This test is performed to check the function of the pituitary gland.
• What is the pituitary gland?
  • It is a small gland in the base of the brain, a few inches behind the bridge of the nose. It has a major role in the control of your body hormone production.
• What do I need to do before the test?
  • You are requested not to eat or drink anything from mid-night on the day of the test.
  • If you are on any medication, withhold taking hormone replacement therapy, e.g. steroid tablets or thyroxine tablets until the test is complete.
• How is this test done?
  • You will be asked to lie flat for the duration of the test.
  • A small needle or cannula will be inserted into a vein in the back of your hand or arm.
  • This is called a 'Venflon' and allows blood samples to be obtained without causing too much discomfort.
  • An initial blood sample will be taken to check the baseline levels of cortisol and growth hormone. (Your blood sugar level will also be checked at the same time.)
  • You will then be given a carefully calculated amount of insulin, which will reduce your blood sugar to a significantly low level.
  • It is essential to achieve a significantly low blood sugar level so as to physiologically stress your brain, which will in turn stimulate your pituitary gland to produce hormones.
  • You may feel a little unwell with shaking, sweating, feel hungry, tired and sleepy when your blood sugar is at a low level. Do not worry as this is only temporary and is anticipated. Be assured though that you will be observed closely and once your blood sugar is low enough to stimulate your pituitary gland, you will be given glucose by injection as needed, to bring your blood sugar back to normal level.
  • Bedside checks of your blood sugar will be done as necessary during the test until your blood sugar is back to normal and stable. Blood samples will be taken through the cannula in your arm at 30 minutes intervals for two hours after the injection of insulin to measure the growth hormone and cortisol response to the insulin induced low sugar stress.
    Note:You will be monitored very closely throughout the test.
  • On completion of the test, the venflon will be removed and you will be offered refreshments.
    (You MUST remember to take your missed morning medication at this time, with food.) It is important that you do have some rest and something to eat before you go home after the test.

  ROUTINE TESTS

  Once you have been diagnosed and your medication regime commenced, you will be followed up regularly and lifelong by your Endocrinologist and GP.
  Addison’s Disease causes the blood potassium to be high and blood sodium to be low due to the lack of aldosterone, therefore proper maintenance treatment requires these regular visits for examinations, laboratory tests and discussions about your symptoms. Certain blood tests, including sodium, potassium, blood counts and plasma renin are very useful in monitoring the response to adjustments in dosage.
  There is no single blood or urine test that is perfect by itself.

  The routine bloods which may be checked are as follows:

  • Full blood count (FBC/CBC)
  • Urea’s and Electrolytes (U’s&E’s) for potassium, sodium, creatinine, etc.
  • Plasma Cortisol
  • Plasma ACTH
  • Plasma Renin (done at your hospital as it requires to “go on ice”)
  • Thyroid Function Test (TSH, T3, T4 and Thyroid Antibodies) is useful since autoimmune Addison’s can cause other glandular problems
  • Glucose

SPECIALISED TESTS

24 HOUR CORTISOL PROFILE / DAY CURVE ANALYSIS

You will normally be admitted to hospital for a 24-hour period, possibly arriving for an 8am admission.
You may have been asked to fast from midnight on the night before your admission and will have been instructed NOT to take your morning dose of medication.

After admission to your ward, an initial blood sample will be drawn. This will give a baseline reading of cortisol levels in your blood. You will then have some breakfast and take your morning medications.

The next stages in the procedure may vary from hospital to hospital.

Either: You will have blood samples drawn every hour for the next 12 hours and then every two hours thereafter. You will take your medication as normal.

Or: You will have further blood samples drawn before lunch and then 1 hour after lunch, before your evening meal and 1 hour afterwards with a final blood sample drawn at bedtime. You will take your medication as normal.

The blood samples will then be analysed and the cortisol levels will be compared to those expected in a 'normal', non-Addisonian person.

From these results, your Consultant will be able to determine if you are on the optimum maintenance dose, or if any changes to dose or times of dose should be made.

INTERPRETING RESULTS

THE SYNACTHEN TEST (STIM.TEST)

Interpreting results and giving the patient the diagnosis and clinical advice is strictly within the province and expertise of the clinican.
For that reason alone we regret we are not able to interpret individual patient's results for them.

However, by listing the normal and/or expected ranges of blood cortisol levels under set conditions, by bringing together examples of these levels which may be found by sometimes extensive search on the internet, and with listings of references to the original published papers from reliable and well respected medical journals, which the patient can look up if they wish, we can assist the reader in understanding results, and the subsequent interpretation put on those results by the clinician.
This may enable the individual patient to ask the pertinent questions of their clinician when they might consider that they need or would like some further explanation.

Normal ranges for blood cortisol.

The units of measurement for many tests varies around the world. The two most popular examples for blood cortisol are those used in USA, and in UK and Australia.
In each case we will give examples of ranges used in all three countries where possible. Please note however that these are only examples cited by individual laboratories, and whilst it may be expected that ranges will be broadly the same, each lab will have established their own particular range for any given test and thus small variations in these ranges are often seen.

Additionally, different doctors put their own interpretation on results, sometimes preferring to use results as a guide and treat symptomatically, whilst others place greater emphasis on these results.

Baseline cortisol

These levels from different labs or hospitals around the world are examples of early morning cortisol levels, ideally around 9am. They are also the equivalent to a random morning cortisol level. (Wording indicating the nature of the test levels below is that of the originating lab or hospital.)

• Australia:
  • Baseline (pre-SynActhen): 200-650nmol/L. (nanomoles/litre)
• USA:
  • AM level: 4.0-22.0µg/dl (micrograms/decilitre)
  • PM level: 3.0-17.0µg/dl
• UK:
  • Hospital #1: Basal cortisol level >150nmol/L.
  • Hospital #2: Cortisol reference range at 9am 200-600nmol/L.

Note:
Whilst no direct conversion factor can be given for correlation of µg/dl against nmol/L. in respect of plasma or serum cortisol estimations, an approximation can be gained by applying a factor of 29.8; thus 10µg/dl is very approximately equal to 298nmol/dl, and vice versa.

Cortisol level 30 minutes after 250mg SynActhen IM

• Australia
  • (....cortisol) to a level of =/>500nmol/L.
• USA:
  • [Data not yet available]
• UK:
  • Hospital #1: (....cortisol) to a level at least 500nmol/L.
  • Hospital #2: Cortisol at least 550nmol/L. after ACTH.

Cortisol increase between pre- & post- SynActhen

• Australia
  • Post-Synacthen: an increase of =/>270nmol/L. over the baseline level
• USA:
  • [Data not yet available]
• UK:
  • Hospital #1: .... the cortisol level at 30 min should show an increment over basal of >200nmol/L
  • Hospital #2: Cortisol increased above pre test result by at least 200nmol/L.

Interpretation:

• Australia
  • "Failure to respond indicates adrenal insufficiency. If basal ACTH is elevated, this suggests primary adrenal failure. Rarely, the test may be done after 3 days of priming the adrenal cortex with 1mg depot Synacthen daily. This allows differentiation between primary adrenocortical failure (no response) and secondary adrenocortical failure."
• USA:
  • [Data not yet available]
• UK:
  • Hospital #1:
    • "A normal response excludes adrenal insufficiency."
    • "A flat or impaired response may indicate the need to progress to one of the prolonged ACTH stimulation tests to elucidated the cause of the adrenal insufficiency."
  • Hospital #2:
    • "All 3(§) criteria must be met for a 'Normal response':-"
      § [baseline level, 30 minute level, and increase i.e. the difference between the two]
    • "Normal response. Usually excludes primary adrenal failure. Secondary Adrenal failure can give normal response."
    • "Failure to increase in cortisol. (Usually from a very low basal level) unequivocally indicates primary adrenal failure."
    • "Blunted response. indicates either primary or secondary adrenal insufficiency. Further assessment may be required prior to committing the patient to cortisol replacement (Prolonged stimulation tests or assay of other steroids)."

References:

• Australia
  • May ME and Carey RM. Am J Med 1985; 79: 679-684.
• UK:
  • Hospital #2:
    • Wood, J.B., Frankland, A.W., James, V.H.T. & Landon, J. (1965) Lancet 1, 243-245
    • Burke, C.W. Adrenocortical insufficiency. (1985) Clin. Endochrinol. Metab. 14, 947-976.
    • Greig, W.R., Maxwell, J.D., Boyle, J.A. (1969) Criteria for distinguishing normal from subnormal adrenocortical function using the Synacthen test. Postgrad Med. J. 45, 307-313
    • Gunneberg, A., Astley, P., Goldie, D.J. (1999) A survey of endocrine function testing by clinical biochemistry laboratories in the UK. Ann. Clin. Biochem., 36, 112.