Testing for Addison’s disease typically starts with a morning blood draw to check cortisol levels, followed by a stimulation test that measures how well your adrenal glands respond to a hormonal signal. The process usually involves two or three appointments and combines blood work, hormone measurements, and sometimes imaging to confirm the diagnosis and identify its cause.
Morning Cortisol and Initial Blood Work
The first step is a simple blood draw, ideally taken early in the morning when cortisol naturally peaks. A morning cortisol level below 5 mcg/dL, combined with a high ACTH level, strongly suggests adrenal insufficiency and may be enough to start treatment while you wait for confirmatory testing. On the other end, a level at or above 18 mcg/dL generally rules it out, though newer, more precise lab assays may use a slightly lower cutoff around 13 to 14 mcg/dL. Many results fall in between, which is why most people need a follow-up stimulation test.
Your doctor will also look at a basic metabolic panel from the same blood draw. Addison’s disease creates a recognizable pattern: low sodium (below 135 mEq/L), high potassium (above 5 mEq/L), low fasting blood sugar, and elevated blood urea nitrogen. High potassium in particular points toward primary adrenal insufficiency rather than a pituitary problem, because potassium only rises when the adrenal glands themselves are failing. If your lab work shows several of these abnormalities together, it raises suspicion even before the cortisol result comes back.
The ACTH Stimulation Test
This is the gold standard for confirming the diagnosis. The Endocrine Society recommends it as the primary diagnostic tool, and it’s straightforward from your perspective. A nurse draws your blood to get a baseline cortisol level, then gives you an injection of synthetic ACTH (a hormone that normally tells your adrenal glands to produce cortisol). The standard dose is 250 micrograms, given in the shoulder muscle or through an IV. After 30 or 60 minutes, your blood is drawn again.
In a healthy person, the adrenal glands respond to this signal by ramping up cortisol production. Your cortisol should rise by at least 7 to 10 mcg/dL from baseline and reach at least 18 mcg/dL at the 60-minute mark. If your cortisol stays flat or barely rises, it confirms your adrenal glands can’t produce enough cortisol even when they receive a strong signal to do so. The test is usually scheduled for 8 or 9 in the morning so results can be compared against established reference ranges collected at that time.
The test itself takes about an hour and a half from start to finish, carries essentially no risk, and is relatively inexpensive compared to alternatives. Some medications can interfere with results, particularly steroid medications like hydrocortisone or prednisone, and hormonal birth control can affect the cortisol binding proteins that some assays measure. Your doctor will likely ask you to stop certain medications beforehand.
Distinguishing Primary From Secondary Causes
Once adrenal insufficiency is confirmed, the next question is where the problem originates. In Addison’s disease (primary adrenal insufficiency), the adrenal glands themselves are damaged. In secondary adrenal insufficiency, the pituitary gland in the brain fails to send the ACTH signal that tells the adrenals to work. The distinction matters because the two conditions require different management approaches.
Plasma ACTH levels, drawn at the same time as the morning cortisol or at baseline during the stimulation test, are the key differentiator. In Addison’s disease, ACTH is elevated, often more than double the upper limit of normal. The pituitary keeps sending louder and louder signals to adrenal glands that can’t respond. In secondary insufficiency, ACTH is low or undetectable because the pituitary itself is the problem. This distinction has about 75% sensitivity and 85% specificity, meaning it’s helpful but not perfect on its own.
One practical clue: high potassium shows up in primary adrenal insufficiency but not in secondary cases. That’s because aldosterone, the hormone that regulates sodium and potassium balance, is controlled partly by a separate signaling system that still works when the pituitary is the issue.
Finding the Underlying Cause
In Western countries, the most common cause of Addison’s disease is autoimmune destruction of the adrenal glands. A blood test for 21-hydroxylase antibodies can confirm this. These antibodies target an enzyme the adrenal glands need to make cortisol, and they’re positive in the vast majority of autoimmune Addison’s cases. They’re also remarkably persistent: more than 90% of patients still test positive 30 years after diagnosis. A positive result essentially confirms the autoimmune origin and may prompt screening for other autoimmune conditions that frequently occur alongside it, like thyroid disease or type 1 diabetes.
If the antibody test is negative, your doctor will look for other causes. A CT scan of the adrenal glands can reveal infections like tuberculosis or fungal disease, which typically show up as enlarged adrenal glands with areas of tissue death and surrounding enhancement. The scan can also identify bleeding into the glands, calcium deposits from old infections, or infiltration by cancer. In tuberculosis-related cases, the glands may appear large and swollen during active infection, then shrink and calcify over time.
Less Common Diagnostic Tests
In specific situations where recent pituitary surgery makes the standard stimulation test unreliable, doctors may use an insulin tolerance test instead. This test deliberately lowers your blood sugar with an insulin injection, which creates a stress response that should trigger cortisol release through the full brain-to-adrenal signaling chain. It’s more informative for detecting very recent pituitary problems because it tests the entire hormonal pathway rather than just the adrenal glands’ ability to respond.
The trade-off is significant: the insulin tolerance test is more expensive, harder to perform, and carries real risk since it involves inducing low blood sugar. For the vast majority of people being evaluated for Addison’s disease, the standard ACTH stimulation test provides the same diagnostic information without these downsides. The insulin tolerance test is reserved for the rare situation where pituitary ACTH deficiency developed recently enough that the adrenal glands haven’t yet shrunk and might still respond normally to synthetic ACTH, giving a falsely reassuring result on the standard test.
What the Full Workup Looks Like
In practice, the diagnostic timeline typically unfolds over a few visits. The first appointment produces your morning cortisol, ACTH, and metabolic panel. If results are suspicious, the ACTH stimulation test is scheduled, sometimes within days if your symptoms are significant. Once insufficiency is confirmed, the antibody test and possibly imaging follow. Most people have a clear diagnosis within two to three weeks of the first blood draw.
If you’re being evaluated during an adrenal crisis, with dangerously low blood pressure and altered electrolytes, the timeline compresses dramatically. A single cortisol level below 18 mcg/dL in that context is considered strong enough evidence to start treatment immediately, with confirmatory testing completed after you’ve stabilized. Doctors can draw baseline cortisol and ACTH before giving you emergency steroids, preserving the diagnostic information even while treating urgently.