Low cortisol causes: why the body makes too little cortisol

Low cortisol has several possible causes, and the first job for a clinician is to find which part of the system has failed. Cortisol is made by the adrenal glands on instructions from the pituitary, which takes its instructions from the hypothalamus. A fault at any of the three can leave you short. Some low blood results also have nothing to do with a failing gland.

The most common cause overall is also the one you can control least on your own. NIDDK says it is suddenly stopping corticosteroids taken for a long time. If you take a steroid medicine, never stop or change it without your prescriber.

Cortisol AM and PM

A morning result and a later one, because cortisol changes through the day. Follow the times on your lab order.

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Not for emergencies. If you have repeated vomiting, severe weakness or fainting, get urgent care instead of ordering a test. If you take a steroid medicine, ask your prescriber how it affects results.

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Causes in the adrenal glands (primary)

Primary adrenal insufficiency means the adrenal glands themselves are damaged. Addison’s disease is the best-known form. Estimates of how common it is differ: about 100 cases per million people in a 2023 review (for Europe), and around 300 per million in a 2025 paper.

Autoimmune disease. The immune system attacks the adrenal glands. NIDDK says this accounts for 8 or 9 of every 10 cases of Addison’s disease in developed countries. A 2025 paper puts it at about 70% in high-income countries. A 2023 review says it appears alongside other autoimmune disorders in more than 60% of cases. It adds that a UK study of more than 22 million people found a raised risk of autoimmune primary adrenal insufficiency with almost any other autoimmune disease.

Infection. NIDDK says tuberculosis used to be the most common cause of Addison’s disease and is much less common now. People with HIV/AIDS are at risk because a weakened immune system can’t fight off infections that damage the glands. The 2023 review also lists sepsis, other bacterial infections, and viral and fungal infections.

Bleeding into the glands. The 2023 review lists adrenal hemorrhage linked to antiphospholipid syndrome, disseminated intravascular coagulation (a clotting disorder) and anticoagulant therapy.

Cancer and other deposits. Tumors in the glands, cancer that has spread to them, lymphoma, and conditions that fill the glands with abnormal material, such as amyloidosis, hemochromatosis and sarcoidosis.

Surgery. Removal of the adrenal glands to treat other conditions. The review lists tumor surgery, removal of both glands (for example to treat Cushing’s syndrome) and radical nephrectomy.

Genetic conditions. NIDDK names inherited disorders that affect how the glands develop or work. The review gives congenital adrenal hyperplasia and X-linked adrenoleukodystrophy as examples.

Causes in the pituitary and hypothalamus (secondary and tertiary)

Secondary adrenal insufficiency means the pituitary isn’t making enough ACTH, the hormone that tells the adrenal glands to make cortisol. A 2014 paper cites estimates that it is about twice as common as the primary form. NIDDK lists these causes:

• Autoimmune disease
• Pituitary tumors or infection
• Bleeding in the pituitary
• Genetic diseases that affect how the pituitary develops or works
• Surgical removal of the pituitary
• Traumatic brain injury

NIDDK points out that the pituitary makes many hormones, so ACTH may not be the only one that is short. A 2026 paper says this kind of adrenal insufficiency, which it calls central, is often diagnosed late because it is subtle.

Tertiary adrenal insufficiency means the hypothalamus isn’t sending enough of its signal to the pituitary. NIDDK names two causes. The first is stopping corticosteroids suddenly after a long course. The second is recovery from Cushing’s syndrome, when the cause of the excess cortisol is removed and the glands are slow to restart.

Medicines that can lower cortisol

Steroid medicines. NIDDK explains the mechanism. Prescription doses can put more steroid in your blood than your body would make. After a long time, the hypothalamus makes less of its signal, the pituitary makes less ACTH and the adrenal glands stop making cortisol. When the medicine stops, the glands may be slow to start again. To give them time, doctors lower the dose gradually over weeks or even months, and recovery can still take many months. A 2024 review adds that inhalers and creams could also suppress the body’s own cortisol. See prednisone, steroids and cortisol results.

Other medicines. NIDDK names certain antifungal medicines and etomidate, an anesthetic. The 2023 review lists these medicine-related causes of primary adrenal insufficiency: ketoconazole, fluconazole, etomidate, mitotane, aminoglutethimide, metyrapone, rifampin, phenytoin, phenobarbital and mifepristone. It also says that adrenal insufficiency has more recently been reported as a side effect of cancer immune checkpoint inhibitor therapy.

A medicine on these lists isn’t a reason to stop it. If you are worried about a medicine you take, ask your prescriber.

When a low result is not a failing gland

A low reading can come from the test itself or from something else going on in the body.

• Time of day. The 2024 review says cortisol falls to its lowest around midnight, so evening values are normally lower than morning ones.
• Carrier proteins. Most cortisol in blood travels attached to a protein. The 2024 review says nephrotic syndrome, a kidney condition, loses that protein and lowers total cortisol. In critically ill people with low albumin, total cortisol was lower while free cortisol was similar. See free vs total cortisol and cortisol-binding globulin.
• The lab method. Different methods give different numbers.
• Early disease. The same review says that in early adrenal insufficiency, residual function can leave cortisol and the response to stimulation tests apparently normal. So a normal result doesn’t always rule the condition out.

That is why doctors don’t act on one number. MedlinePlus says a cortisol test alone can’t identify the cause of an abnormal level, and that more tests usually follow.

Does low cortisol cause anxiety, headaches or insomnia?

Those are questions about symptoms, not causes. NIDDK lists irritability and depression among the symptoms of adrenal insufficiency. It doesn’t list anxiety, headaches or trouble sleeping. All three have many common causes. See low cortisol symptoms.

Who is more likely to have it

• People who have taken steroid medicine for a long time, especially if it was stopped suddenly.
• People with another autoimmune disease.
• People with pituitary tumors, pituitary surgery or a traumatic brain injury.
• People with HIV/AIDS or tuberculosis.

Sex matters a little. Autoimmune disease is more common in women, and the 2014 paper notes that women are assumed to make up most people with Addison’s disease. See low cortisol in women and men.

How doctors find the cause

NIDDK says doctors first confirm that cortisol is low, then look for the cause. For primary adrenal insufficiency that can include:

• A blood test for the antibodies seen in autoimmune Addison’s disease.
• A CT scan of the abdomen to look at the adrenal glands.
• Tests for tuberculosis.

For secondary and tertiary cases, an MRI looks at the pituitary and hypothalamus. A 2023 review describes pairing serum cortisol with plasma ACTH as the next step when the primary form is suspected. See the ACTH blood test.

If you are thinking about ordering a test

A cortisol blood test is a first look, and it won’t tell you the cause. A morning cortisol with a later sample is a reasonable thing to bring to a clinician if you have no emergency signs. The seller’s page for its AM and PM test is unclear about when the second sample is taken and doesn’t say whether it is one visit or two, so follow the timing on your lab order and check it before you order. If you take a steroid medicine, tell your prescriber before you test, and don’t change the medicine for a test.