The endocrine system is complex and testing procedures often misunderstood.
For example, diagnostic recommendations for adrenal insufficiency evolved as different testing methods became available. At one point the ACTH stimulation test was in use, but there was no way to measure pituitary ACTH production. Without the ACTH level to assess the pituitary, diagnosing secondary adrenal insufficiency was very difficult. This led to the discussion among professionals about whether the high or low dose ACTH stim test was better to diagnose secondary AI. Those discussions are still in the literature used today. We now have the ACTH baseline measurement to help differentiate between primary and secondary AI. Physicians who see the older discussions on the ACTH stim test often miss the importance of the ACTH baseline for diagnosing SAI.
Diagnosis of adrenal insufficiency is a three-stage process.
- Demonstrating a cortisol deficiency.
- Evaluating whether the cortisol deficiency originates in the adrenal glands, or is caused by an ACTH deficiency from the pituitary gland.
- Testing for mineralocorticoid deficiency in patients without an ACTH deficiency.
Tests used to evaluate the HPA axis.
The morning serum cortisol checks baseline adrenal cortisol production. It should be drawn between 8 and 9am.
The baseline ACTH test evaluates pituitary corticotropin, (ACTH) production. It should be drawn simultaneously with the morning cortisol sample.
The ACTH stimulation test evaluates stimulated adrenal cortisol response. This test is used to confirm or exclude PAI if the baseline cortisol result is indeterminate. Lack of appropriate response may indicate adrenal atrophy in chronic SAI patients. Adequate response to the ACTH stimulation test does not eliminate the possibility of secondary or tertiary AI.
The Metyrapone and the Insulin Tolerance Test (ITT), are used to measure stimulated pituitary ACTH production if SAI or TAI is suspected. Choice of which test to use is based on patient profile. Current recommendations favor the Metyrapone. It is more accurate, less expensive, and easier to administer than the ITT.
Adrenal Imaging, CT Scan
Pituitary Imaging, MRI
Initial testing for adrenal insufficiency can be simple and labs ordered by any physician. The morning cortisol and the baseline ACTH sampled and interpreted together, should indicate the direction for further testing and/or referral to a specialist.
The ACTH stimulation test is often ordered first. It is important to request that the baseline ACTH is sampled BEFORE the injection. If the problem originates in the pituitary or hypothalamus, it can go undetected by the ACTH stim test alone, leading to misdiagnosis.
The following hormones or drugs may interfere with accurate test results.
- Glucocorticoids or corticosteroids in any form, including topical, inhaled, injected, and oral tablets/capsules.
• Birth control or other estrogens, including soybean food products and menopause formulas.
• Drugs that inhibit cortisol biosynthesis, such as etomidate, ketoconazole, fluconazole, metyrapone, and suramin.
• Drugs that accelerate the metabolism of cortisol and most synthetic glucocorticoids by inducing hepatic mixed-function oxygenase enzymes, such as phenytoin, barbiturates, mitotane, and rifampin.
• High dose progestins or chronic administration of opiates.
Recommended times for discontinuing steroids before testing are 12 hours for Hydrocortisone, 24 hours for Prednisone.
Dexamethasone is commonly prescribed for patients suspected of adrenal insufficiency who require testing to confirm the diagnosis. It is not read by radioimmunoassay, the most common type of lab test for cortisol. This is an accurate way to assess HPA axis function provided that testing is done within the first two weeks of treatment. After this time period Dexamethasone will begin to suppress HPA axis function.
For more information on testing after HPA axis suppression has occurred, please see our “Glucocorticoid tapering and adrenal suppression testing guide” in the research library.
A brochure on testing you can share with your doctor can be printed here. (link for AI, AF, Cushing’s brochure)
Electrolyte balance is an important part of managing adrenal insufficiency. Primary AI patients occasionally have an aldosterone deficiency. Florinef or Fludrocort, mineralocorticoid steroids, are prescribed to help regulate sodium and potassium. Secondary and tertiary patients often have their own unique electrolyte issues to address, although there is no typical pattern. Because electrolyte imbalances can be life-threatening, it’s important to discuss them with your doctor and have them tested. Aldosterone/plasma renin activity, (PRA) is the correct test to evaluate mineralocorticoid deficiency. A standard Comprehensive metabolic profile, (CMP) will show potassium and sodium levels, and the RBC magnesium test is used to assess magnesium.
Current guidelines for the testing, treatment, and management of Primary, secondary, and tertiary forms of adrenal insufficiency can be found in our research library.