Adrenal gland problems fall into two broad categories: the glands produce too little hormone, or they produce too much. The causes range from autoimmune attacks and genetic conditions to tumors, long-term medication use, and problems originating outside the adrenal glands entirely. Understanding which type of problem is at play matters because the symptoms, risks, and treatments differ significantly.
Autoimmune Destruction: The Leading Cause of Adrenal Failure
The most common reason the adrenal glands stop working in developed countries is an autoimmune attack, accounting for up to 90% of cases of primary adrenal insufficiency (also called Addison’s disease). The immune system mistakenly targets a protein called 21-hydroxylase, which the adrenal glands need to produce cortisol and aldosterone. Over time, this attack damages enough adrenal tissue that the glands can no longer keep up with the body’s demand for these hormones.
Cortisol helps regulate blood sugar, blood pressure, and the body’s stress response. Aldosterone controls sodium and potassium balance. When both drop too low, symptoms creep in gradually: fatigue, weight loss, low blood pressure, salt cravings, and darkening of the skin. Because these symptoms develop slowly and overlap with many other conditions, Addison’s disease often goes undiagnosed for months or even years.
Long-Term Steroid Use
Taking cortisol-like medications (glucocorticoids such as prednisone) for extended periods is one of the most common causes of adrenal problems, and it can cause trouble in two different directions. While you’re taking high doses, the excess cortisol-like activity can lead to Cushing’s syndrome, with symptoms like weight gain concentrated in the face and midsection, thinning skin, easy bruising, and muscle weakness.
The other problem happens when you stop. Long-term steroid use tells the brain to stop signaling the adrenal glands to make their own cortisol. The glands essentially go dormant. If you suddenly stop taking the medication, your body has no cortisol supply at all, which can trigger a dangerous drop in blood pressure and blood sugar called an adrenal crisis. This is why doctors taper steroid doses gradually rather than stopping them abruptly.
Pituitary and Brain-Related Causes
The adrenal glands don’t operate independently. They take orders from the pituitary gland at the base of the brain, which sends a signaling hormone called ACTH to tell the adrenals how much cortisol to produce. Anything that disrupts this communication chain causes what’s known as secondary adrenal insufficiency, where the adrenal glands themselves are healthy but aren’t receiving the signal to work.
Pituitary tumors are a common culprit. Even benign growths can compress the tissue responsible for producing ACTH. Traumatic brain injury, pituitary surgery, and radiation therapy to the head can also damage this signaling pathway. The resulting hormone deficiency looks similar to Addison’s disease (fatigue, weakness, low blood pressure) but typically without the skin darkening, since that symptom is driven by excess ACTH rather than a lack of it.
Tumors and Growths on the Adrenal Glands
Adrenal tumors are surprisingly common. With modern high-resolution CT scanners, incidental adrenal masses show up on 1.4% to 7.3% of abdominal scans, and that number climbs to roughly 10% in older adults. The vast majority of these “incidentalomas” are benign and inactive, meaning they don’t produce excess hormones and don’t require treatment. But a subset of adrenal tumors are hormonally active, and these cause distinct problems depending on which hormone they overproduce.
Tumors that pump out excess cortisol cause Cushing’s syndrome. Tumors called pheochromocytomas produce surges of adrenaline and noradrenaline, leading to episodes of severe high blood pressure, rapid heartbeat, sweating, and headaches. These episodes can be triggered by physical exertion, certain foods, or even emotional stress, and they carry real cardiovascular risk if left untreated.
Another type of adrenal tumor overproduces aldosterone, the hormone that regulates salt and potassium. This condition, called primary aldosteronism, is now recognized as the most common secondary cause of high blood pressure. It’s estimated to affect 5% to 10% of adults with hypertension, though recent research suggests the true number may be at least three times higher because milder forms often go undetected by standard screening.
Genetic and Inherited Conditions
Some adrenal problems are present from birth. The most common inherited adrenal disorder is congenital adrenal hyperplasia, usually caused by a deficiency of the 21-hydroxylase enzyme. This enzyme is essential for producing cortisol and aldosterone. When it’s missing or deficient, the raw materials that would normally become cortisol and aldosterone instead get converted into androgens (male sex hormones).
The result is a combination of problems: too little cortisol, potentially too little aldosterone (leading to dangerous salt loss in severe forms), and too many androgens. Excess androgens can cause differences in genital development in newborns and early puberty in children. Most cases are caught through newborn screening programs, and lifelong hormone replacement keeps the condition well managed.
Pheochromocytomas also have a genetic component. Some cases are linked to inherited syndromes that run in families, making genetic testing relevant for anyone diagnosed with one of these tumors, especially at a young age.
Infections and Physical Damage
Before autoimmune disease became the dominant cause of adrenal failure in developed countries, infections were the primary culprit, and they still are in parts of the world where tuberculosis is widespread. TB can infiltrate and destroy adrenal tissue over time. Fungal infections and HIV can also damage the glands.
Less commonly, the adrenal glands can be damaged by bleeding into the gland tissue (adrenal hemorrhage), which sometimes occurs during severe infections or in people on blood-thinning medications. Surgical removal of the adrenal glands, whether for tumor treatment or other reasons, obviously eliminates hormone production from that gland as well.
What Triggers an Adrenal Crisis
For people who already have adrenal insufficiency, whether diagnosed or not, certain stressors can push the body into an adrenal crisis. This is a medical emergency where cortisol levels drop so low that blood pressure collapses and the body can’t maintain basic functions. Common triggers include infections (even a bad flu), surgery, pregnancy, severe dehydration, and emotional stress. Abruptly stopping long-term glucocorticoid medications is another frequent cause.
People with known adrenal insufficiency are typically taught to increase their replacement hormone dose during illness or physical stress to prevent a crisis. Those who don’t yet know they have an adrenal problem are at highest risk, because the crisis may be the first sign that something is wrong.
“Adrenal Fatigue” vs. Adrenal Insufficiency
The term “adrenal fatigue” circulates widely online, described as a state where chronic stress supposedly exhausts the adrenal glands until they can no longer produce adequate hormones. The proposed symptoms are nonspecific: tiredness, weakness, sleep problems, cravings for sugar and salt. However, there is no scientific evidence supporting this theory. No study has demonstrated that chronic stress causes the adrenal glands to “burn out” in the way proponents describe, and existing hormone tests don’t show the pattern this theory predicts.
Adrenal insufficiency, on the other hand, is a well-defined medical condition that can be diagnosed through blood tests and stimulation tests. In a standard stimulation test, a synthetic version of the pituitary signaling hormone is injected, and cortisol levels are measured afterward. A peak cortisol level below roughly 15 to 16 mcg/dL indicates the adrenal glands aren’t responding properly. Imaging with CT or MRI can then help identify the underlying cause. If you’re experiencing persistent fatigue and the other symptoms described above, getting a proper workup matters, because attributing symptoms to a vague label like adrenal fatigue can delay diagnosis of a real, treatable condition.