Adrenal insufficiency is a condition where your adrenal glands don’t produce enough of certain essential hormones, most importantly cortisol. Cortisol helps regulate blood pressure, blood sugar, metabolism, and your body’s response to stress. Without enough of it, even routine physical demands like fighting off a cold can become dangerous. The condition affects roughly 4 to 11 people per 100,000, and it comes in several forms depending on where in the body the problem originates.
The Three Types of Adrenal Insufficiency
Your cortisol production depends on a chain of signals that starts in the brain and ends at the adrenal glands, which sit on top of your kidneys. The hypothalamus (a small region in the brain) tells the pituitary gland to release a signaling hormone called ACTH, and ACTH tells the adrenal glands to make cortisol. A problem at any point in this chain causes a different type of adrenal insufficiency.
Primary adrenal insufficiency (also called Addison’s disease) means the adrenal glands themselves are damaged and can’t produce enough cortisol or aldosterone, a hormone that controls salt and water balance. This is the rarest form, with about 6 new cases per million people each year. The most common cause in developed countries is an autoimmune reaction where the body’s immune system attacks the adrenal glands. Infections like tuberculosis, bleeding into the adrenal glands, and certain genetic conditions can also cause it.
Secondary adrenal insufficiency starts in the pituitary gland. If the pituitary doesn’t produce enough ACTH, the adrenal glands never get the signal to make cortisol. Over time, the unstimulated adrenal glands can actually shrink. Pituitary tumors, surgery on the pituitary, radiation to the brain, and a condition called Sheehan syndrome (where the pituitary is damaged by blood loss during childbirth) are common causes.
Tertiary adrenal insufficiency is the most common form overall, and it starts in the hypothalamus. The single biggest cause is stopping long-term steroid medications (like prednisone) too abruptly. These medications are widely prescribed for asthma, rheumatoid arthritis, lupus, and inflammatory conditions. When taken for extended periods, they suppress the hypothalamus, which “forgets” how to signal for cortisol production. Stopping suddenly leaves the body without a way to make its own cortisol.
Common Symptoms
The symptoms of adrenal insufficiency often develop gradually, which is one reason the condition is frequently missed or misdiagnosed for months. Fatigue, weakness, and unexplained weight loss are typically the earliest signs. Many people also experience nausea, vomiting, abdominal pain, dizziness when standing up, and muscle or joint pain. Low blood sugar episodes are common because cortisol plays a key role in maintaining glucose levels.
One distinctive sign of primary adrenal insufficiency is darkening of the skin, particularly in skin creases, on the palms, around scars, on the nipples, and inside the mouth. This happens because when the adrenal glands fail, the pituitary floods the body with ACTH to try to compensate. ACTH is produced alongside another chemical that stimulates the cells responsible for skin pigmentation. The result is a bronzed or tanned appearance that develops without sun exposure. This darkening does not occur in secondary or tertiary adrenal insufficiency because in those forms, ACTH levels are low rather than high. People with secondary insufficiency often have unusually pale skin instead.
Salt cravings are another hallmark of primary adrenal insufficiency specifically, because the damaged adrenal glands also stop producing aldosterone. Without aldosterone, the kidneys lose too much sodium, driving intense cravings and causing low blood sodium levels paired with elevated potassium. In secondary and tertiary forms, aldosterone production is usually preserved because it’s regulated by a separate system.
How It’s Diagnosed
The standard diagnostic test is the ACTH stimulation test. A synthetic version of ACTH is injected, and blood cortisol levels are measured 30 to 60 minutes later. Historically, a cortisol response below 18 micrograms per deciliter was considered diagnostic. However, newer, more precise lab assays have led researchers to recommend a lower cutoff of around 14 to 15 micrograms per deciliter, since the old threshold was producing false positives with modern testing equipment.
Blood tests also check ACTH levels, which help distinguish between the types. In primary adrenal insufficiency, ACTH is very high because the pituitary is working overtime trying to stimulate the failing adrenal glands. In secondary and tertiary forms, ACTH is low or inappropriately normal. Electrolyte panels often reveal low sodium and high potassium in primary cases. Imaging of the adrenal glands or pituitary may follow depending on the suspected cause.
Treatment and Daily Management
Treatment replaces the hormones your body can no longer make in sufficient quantities. The standard replacement is hydrocortisone, typically 15 to 25 milligrams per day split into two or three doses. The goal is to mimic the body’s natural cortisol rhythm, with a larger dose in the morning and smaller doses later in the day. Some people take prednisolone or cortisone acetate as alternatives.
People with primary adrenal insufficiency also need a mineralocorticoid replacement to compensate for lost aldosterone production. This helps the body retain sodium and maintain blood pressure. The dose is adjusted based on blood pressure readings and lab results. Secondary and tertiary forms generally don’t require mineralocorticoid replacement.
Living with adrenal insufficiency requires learning to adjust your medication during times of physical stress, commonly known as “sick day rules.” These are straightforward but critical:
- Fever above 38°C (100.4°F) or illness requiring bed rest: double your oral steroid dose for at least 72 hours
- Fever above 39°C (102.2°F): triple your oral dose
- Infections requiring antibiotics or minor procedures like dental work: double the dose
- Severe illness, trauma, persistent vomiting, or surgery: an injectable steroid dose is needed because pills may not be absorbed
If symptoms don’t improve after 72 hours of increased dosing, contact your physician. Mineralocorticoid doses do not need to be changed during illness.
Adrenal Crisis
The most dangerous complication of adrenal insufficiency is an adrenal crisis, a life-threatening drop in cortisol that the body cannot compensate for. It can be triggered by an infection, surgery, injury, severe emotional stress, or simply missing medication doses. Symptoms escalate quickly: severe abdominal pain, vomiting, profound weakness, confusion, dangerously low blood pressure, and eventually collapse or loss of consciousness. Some people experience back and leg cramps, high fever, or delirium.
An adrenal crisis requires emergency treatment with an immediate injection of 100 milligrams of hydrocortisone, followed by continued high-dose hydrocortisone over the next 24 hours along with intravenous fluids. Most people with adrenal insufficiency are advised to carry an emergency injection kit and wear a medical alert bracelet or necklace so that first responders can identify the condition quickly. Teaching close family members or partners how to administer the injection can be lifesaving when the person in crisis is too confused or weak to do it themselves.
Why the Type Matters
Knowing which type of adrenal insufficiency you have shapes both treatment and monitoring. Primary adrenal insufficiency is usually a lifelong condition requiring both cortisol and aldosterone replacement, with periodic screening for other autoimmune conditions since they tend to cluster together. Secondary adrenal insufficiency caused by a pituitary tumor may improve after the tumor is treated. Tertiary adrenal insufficiency from steroid withdrawal is often reversible, though recovery of the hypothalamic-pituitary-adrenal axis can take months to over a year. During that recovery period, stress dosing rules still apply, and medication is tapered very gradually under medical supervision rather than stopped all at once.