Addison’s disease is diagnosed through a combination of blood tests that measure hormone levels, with the ACTH stimulation test serving as the primary diagnostic tool. The process typically starts with a simple morning blood draw and, if results are concerning, moves to more specialized testing to confirm the diagnosis and pinpoint its cause.
Initial Blood Tests
Diagnosis often begins before anyone suspects Addison’s disease. Routine blood work frequently reveals the first clues: low sodium or high potassium levels that prompt further investigation. These electrolyte imbalances happen because the adrenal glands aren’t producing enough of the hormones that regulate salt and water balance in your body.
If your doctor suspects adrenal insufficiency based on your symptoms or those initial labs, the next step is a morning blood draw to check your cortisol level. Cortisol naturally peaks in the early morning, so this is the best window to assess whether your adrenal glands are functioning. A morning cortisol below about 3.5 mcg/dL (100 nmol/L) strongly suggests adrenal insufficiency and may be enough on its own to support the diagnosis. On the other end, a level above roughly 16 mcg/dL (450 nmol/L) generally rules it out. Most people fall somewhere in between, which is where stimulation testing becomes necessary.
The ACTH Stimulation Test
The ACTH stimulation test is the most commonly used test to confirm Addison’s disease. ACTH is the hormone your pituitary gland sends to tell your adrenal glands to produce cortisol. During this test, you receive a synthetic version of ACTH by injection, then have your blood drawn 30 to 60 minutes later to see how your adrenal glands responded.
In a healthy person, cortisol rises significantly after the injection. The expected peak is above 15 to 16 mcg/dL (430 to 450 nmol/L), though the exact cutoff depends on the lab’s assay method and the dose used. In someone with Addison’s disease, cortisol barely rises or doesn’t rise at all. The adrenal glands are too damaged to respond to the signal, no matter how strong it is.
Distinguishing Primary From Secondary Causes
Once adrenal insufficiency is confirmed, your doctor needs to determine whether the problem originates in the adrenal glands themselves (primary adrenal insufficiency, which is Addison’s disease) or in the pituitary gland, which controls the adrenals (secondary adrenal insufficiency). The distinction matters because the causes, treatment, and monitoring differ.
Measuring your plasma ACTH level is the standard way to tell them apart. In Addison’s disease, ACTH is typically very high because the pituitary keeps sending stronger and stronger signals to adrenal glands that can’t respond. Studies show median ACTH levels around 251 pg/mL in primary adrenal insufficiency, compared to about 9 pg/mL in secondary cases. An ACTH level above the upper limit of normal identifies primary disease with roughly 75% sensitivity and 85% specificity.
If results from the ACTH stimulation test are unclear and secondary adrenal insufficiency is suspected, an insulin tolerance test may be ordered. This test is considered the gold standard for identifying secondary disease. It works by lowering your blood sugar with insulin, which should trigger a stress response that raises cortisol. If cortisol doesn’t rise appropriately, it points to a pituitary problem. This test isn’t suitable for everyone, though. It’s avoided in people with heart disease, seizure disorders, or severe thyroid problems.
Identifying the Underlying Cause
In Western countries, the most common cause of Addison’s disease is autoimmune destruction of the adrenal glands. To confirm this, doctors test for antibodies against an enzyme called 21-hydroxylase, which the adrenal glands need to produce cortisol. These antibodies are present in the vast majority of autoimmune cases and remain detectable for decades. More than 90% of patients still test positive 30 years after diagnosis. That said, a negative result in someone who has had the disease for a long time doesn’t completely rule out an autoimmune cause, since antibody levels can occasionally fade.
Antibody levels can also vary depending on age at diagnosis, sex, and whether Addison’s disease occurs on its own or alongside other autoimmune conditions (a pattern called autoimmune polyendocrine syndrome).
When autoimmune testing is negative, imaging comes into play. A CT scan of the adrenal glands can reveal causes like tuberculosis or fungal infections, which typically show bilateral adrenal enlargement with areas of tissue death and surrounding enhancement. In long-standing autoimmune disease, the glands may instead appear shrunken. Adrenal calcification on imaging can point to prior infection as the original trigger.
Checking Aldosterone and Renin
Cortisol isn’t the only hormone the adrenal glands produce. In Addison’s disease, production of aldosterone, the hormone that regulates sodium and potassium balance, also drops. To assess this, doctors measure both aldosterone and renin levels, usually together. Renin is a hormone released by the kidneys that signals the adrenals to make aldosterone. When aldosterone is low, renin rises as the body tries to compensate. This combination of low aldosterone and high renin is characteristic of primary adrenal insufficiency and helps distinguish it from secondary forms, where aldosterone production is typically preserved because it’s regulated by a separate pathway.
What the Diagnostic Process Looks Like
For most people, the path to diagnosis follows a predictable sequence. It starts with blood work showing low cortisol, abnormal electrolytes, or both. An ACTH stimulation test confirms that the adrenal glands aren’t functioning properly. ACTH levels help locate the problem. Then antibody testing and possibly imaging identify the cause. The entire workup can often be completed within a few visits, though some tests require morning timing or fasting.
One practical reality worth knowing: Addison’s disease is rare enough that it’s frequently missed or delayed. Symptoms like fatigue, weight loss, low blood pressure, and skin darkening overlap with many other conditions. The average time from first symptoms to diagnosis can stretch months or even years. If your blood tests have shown borderline cortisol or unexplained electrolyte problems, pushing for an ACTH stimulation test is reasonable. It’s a straightforward, low-risk procedure that provides a clear answer.