Testing for Addison’s disease typically starts with a morning blood draw to measure cortisol, followed by a stimulation test that checks whether your adrenal glands can respond to a hormonal signal. A morning cortisol level below 3 mcg/dL strongly suggests adrenal insufficiency, while a normal response to the stimulation test effectively rules it out. The full diagnostic process usually involves several layers of testing to confirm the diagnosis and pinpoint the cause.
Morning Cortisol: The First Clue
Cortisol naturally peaks between 6 and 8 a.m., which makes an early morning blood draw the most informative starting point. A level below 3 mcg/dL at 8 a.m. is a strong indicator of adrenal insufficiency. Higher levels don’t necessarily clear you, though. Values in the middle range often need further investigation, which is where stimulation testing comes in.
Because cortisol is sensitive to stress and physical activity, you may be asked to rest quietly before the blood draw. If you take any steroid medications, including skin creams, let your provider know. These can artificially raise cortisol levels and mask a true deficiency.
The ACTH Stimulation Test
This is the gold standard for diagnosing Addison’s disease. A healthcare provider injects a synthetic version of ACTH, the pituitary hormone that normally tells your adrenal glands to produce cortisol. Your blood is drawn before and after the injection (typically at 30 or 60 minutes) to see how your adrenals respond.
In a healthy person, cortisol rises to at least 15 to 16 mcg/dL after the injection. If your cortisol stays flat or barely budges, your adrenal glands aren’t functioning properly. This test is quick, safe, and gives a clear answer in most cases. It’s usually the single most important step in confirming or ruling out Addison’s disease.
Telling Primary From Secondary Insufficiency
Addison’s disease specifically refers to primary adrenal insufficiency, where the adrenal glands themselves are damaged. But similar symptoms can occur when the pituitary gland fails to send the ACTH signal in the first place, which is called secondary adrenal insufficiency. The treatment and long-term outlook differ, so distinguishing the two matters.
A plasma ACTH level drawn alongside cortisol does most of the work here. In primary Addison’s disease, ACTH is typically very high because the pituitary is working overtime trying to stimulate unresponsive adrenals. Median levels in studies of primary insufficiency run around 251 pg/mL, far above the normal upper limit of about 46 pg/mL. In secondary insufficiency, ACTH is low or undetectable, with median levels around 9 pg/mL, because the pituitary itself is the problem.
If the ACTH stimulation test results are ambiguous, a CRH stimulation test can help clarify things further. CRH is the brain hormone one step upstream from ACTH. After an IV injection of CRH, blood samples are taken at 30, 60, 90, and 120 minutes. If the pituitary is damaged, it won’t produce ACTH in response, confirming secondary insufficiency. A slow, delayed rise in ACTH instead points to a problem at the hypothalamus level, called tertiary insufficiency.
Blood Chemistry Patterns That Raise Suspicion
Addison’s disease is often first suspected not from hormone testing but from routine blood work that shows an unusual electrolyte pattern. The adrenal glands produce aldosterone, a hormone that regulates sodium and potassium balance. When the glands fail, sodium drops and potassium rises. A classic presentation is persistent low sodium (hyponatremia) alongside potassium levels at the upper edge of normal or above it. One published case series documented sodium as low as 125 mmol/L with potassium at 5.5 mmol/L.
These electrolyte shifts can also cause low blood pressure, dizziness, and salt cravings, symptoms that often bring people to their doctor in the first place. If you have unexplained low sodium on routine labs, especially combined with fatigue and weight loss, your provider should consider adrenal insufficiency as a possible explanation.
Finding the Underlying Cause
Once Addison’s disease is confirmed, the next step is figuring out why the adrenal glands are failing. In developed countries, the most common cause is autoimmune destruction, where the immune system attacks the adrenal cortex.
A blood test for antibodies against an enzyme called 21-hydroxylase can confirm this. These antibodies are present in most people with autoimmune Addison’s and can actually appear years before symptoms develop. In screening studies, about 0.6% of people tested positive for these antibodies persistently. Among those who eventually progressed to full-blown disease, antibody levels were significantly higher than in those who didn’t, though the antibodies alone can’t predict exactly when someone will become symptomatic.
When autoimmune testing comes back negative, imaging enters the picture. A CT scan of the adrenal glands can reveal structural problems. In tuberculosis or fungal infections affecting the adrenals, the glands are typically enlarged on both sides, with areas of tissue death visible as dark spots surrounded by enhanced tissue on contrast imaging. In longstanding autoimmune disease, the glands tend to look shrunken instead. Calcification of the adrenals is another finding that can point to prior infection.
Less Common Tests
The insulin tolerance test exists as an alternative but is rarely used today. It works by inducing low blood sugar through an insulin injection, which creates a stress response that should trigger cortisol release through the entire hormonal chain from brain to adrenal gland. It’s more difficult to perform, carries more risk, and costs more than the standard ACTH stimulation test.
The main scenario where it still has a role is shortly after pituitary surgery. In the first month or two after an operation on the pituitary gland, the adrenals haven’t had time to shrink yet, so they may still respond normally to the ACTH stimulation test even if ACTH production is now impaired. The insulin tolerance test can catch this gap because it tests the entire signaling chain rather than just the adrenal response.
What the Testing Process Looks Like
For most people, the diagnostic workup unfolds over a few visits. An initial blood draw covers morning cortisol, ACTH, and basic electrolytes. If those results are suspicious, the ACTH stimulation test is scheduled, which takes about an hour and involves a single injection plus two or three blood draws. Results typically come back within a few days.
If the diagnosis is confirmed, antibody testing and possibly a CT scan follow to establish the cause. The entire process from first suspicion to confirmed diagnosis can take anywhere from a week to several weeks, depending on how quickly tests are ordered and results returned. If you’re experiencing symptoms like profound fatigue, darkening skin, low blood pressure, or unexplained weight loss, bringing up adrenal insufficiency with your provider can help move the process along faster.