Secondary adrenal insufficiency is a condition where your adrenal glands don’t produce enough cortisol because the pituitary gland, located at the base of the brain, fails to send the right signal. That signal is a hormone called ACTH, which normally tells the adrenal glands how much cortisol to make. When ACTH levels drop too low, cortisol production falls with it. The most common reason this happens is prolonged use of steroid medications like prednisone, though pituitary tumors and other conditions can also be responsible.
How It Differs From Primary Adrenal Insufficiency
In primary adrenal insufficiency (Addison’s disease), the adrenal glands themselves are damaged and can’t produce cortisol regardless of how much signaling they receive. In secondary adrenal insufficiency, the adrenal glands are intact but understimulated. The problem sits higher up in the chain: the pituitary gland isn’t releasing enough ACTH.
This distinction matters because the two conditions look different. People with primary adrenal insufficiency often develop darkened skin, especially on the knuckles, elbows, and gums, because the pituitary overproduces ACTH in a desperate attempt to stimulate the adrenals, and that excess ACTH triggers pigment production. In secondary adrenal insufficiency, ACTH is low, so skin darkening doesn’t occur. People with the secondary form are also less likely to become dehydrated or develop high potassium levels, because the adrenal glands still produce aldosterone (the hormone that manages salt and fluid balance) largely independently of ACTH. Low blood sugar, however, is more common in the secondary form.
Common Causes
By far the most frequent cause is long-term use of glucocorticoid medications, steroids prescribed for conditions like asthma, rheumatoid arthritis, and inflammatory bowel disease. When you take these drugs, they replace your body’s own cortisol, and the pituitary gland responds by scaling back ACTH production. Over time, this signaling pathway essentially goes dormant. The Endocrine Society guidelines indicate that oral steroid use exceeding 3 to 4 weeks at doses above roughly 4 to 6 mg of prednisone daily (or equivalent) poses a real risk of suppressing this system. Shorter courses, even at high doses, rarely cause lasting suppression, and steroids can generally be stopped abruptly if used for less than 3 to 4 weeks.
The other major category involves direct damage to the pituitary gland. Pituitary tumors are the most common structural cause, but surgery to remove those tumors, radiation therapy to the head or brain, traumatic brain injury, and rare infections or inflammatory diseases (granulomas) can also destroy enough pituitary tissue to reduce ACTH output. When multiple pituitary hormones are affected at once, the broader condition is called panhypopituitarism.
Symptoms to Recognize
Cortisol affects nearly every organ system, so the symptoms of secondary adrenal insufficiency are widespread and often vague, which makes the condition easy to miss. The hallmark complaints are persistent fatigue, low blood pressure (sometimes causing dizziness when standing), unexplained weight loss, and poor appetite. Nausea, vomiting, and recurring abdominal pain are common. Some people notice mental fogginess or changes in mood.
Women may experience missed periods, reduced sex drive, and thinning of underarm and pubic hair, because the adrenal glands also produce weak androgens that depend partly on ACTH stimulation. Symptoms tend to develop gradually over weeks to months and often worsen during physical stress like illness or injury, when the body’s demand for cortisol spikes.
How It’s Diagnosed
Diagnosis starts with measuring morning cortisol levels in the blood. A very low morning cortisol strongly suggests adrenal insufficiency, but borderline results require further testing. The standard next step is the ACTH stimulation test: a synthetic version of ACTH is injected, and cortisol is measured 30 and 60 minutes later. A peak cortisol level below roughly 14 to 18 micrograms per deciliter (depending on the lab’s assay) points toward adrenal insufficiency. About 20 percent of healthy people with already-high baseline cortisol won’t show much of a rise after the injection, so the absolute peak matters more than how much cortisol increases.
There’s an important caveat with this test for secondary cases. If the pituitary has only recently stopped producing ACTH, the adrenal glands haven’t had time to shrink yet and may still respond normally to the injected ACTH. This can produce a falsely reassuring result early in the course of the disease. The gold standard for confirming secondary adrenal insufficiency is the insulin tolerance test, which induces controlled low blood sugar to provoke a full stress response from the brain and adrenals. It’s highly accurate but requires close medical supervision and is not safe for people with a history of seizures or heart disease.
Daily Hormone Replacement
Treatment centers on replacing the cortisol your body can’t make on its own. The standard replacement is oral hydrocortisone at 15 to 25 mg per day, split into two or three doses to mimic the body’s natural cortisol rhythm (higher in the morning, lower in the evening). Alternatives include prednisolone at 3 to 5 mg daily or cortisone acetate at 20 to 35 mg daily. Some researchers have argued that even the lower end of the hydrocortisone range may be slightly more than the body actually needs, based on updated measurements of how much cortisol healthy people produce each day, so there’s a trend toward using the lowest effective dose.
Unlike primary adrenal insufficiency, most people with the secondary form do not need a separate medication for aldosterone replacement, since that hormone pathway remains functional.
For people whose condition was caused by steroid medications, recovery is possible but slow. Once the external steroids are tapered and stopped, the pituitary’s ACTH production can gradually resume, sometimes taking months to over a year. During this recovery window, cortisol replacement and careful monitoring remain essential.
Sick Day Rules and Adrenal Crisis
The most dangerous complication is adrenal crisis, a sudden, severe cortisol shortage that can cause dangerously low blood pressure, confusion, and collapse. This happens when the body faces physical stress (infection, surgery, injury) and can’t ramp up cortisol production to meet the demand. Approximately 5 to 17 episodes of adrenal crisis occur per 100 patient-years among people with adrenal insufficiency, making it a real and recurring risk rather than a rare event.
Two “sick day rules” help prevent crisis:
- Rule 1: Double your daily oral glucocorticoid dose during any illness with fever that puts you in bed or requires antibiotics.
- Rule 2: If you’re vomiting, have prolonged diarrhea, are preparing for a colonoscopy, or face acute trauma or surgery, glucocorticoids need to be given by injection because oral doses won’t be absorbed reliably.
Most people with secondary adrenal insufficiency carry an emergency injection kit and wear a medical alert bracelet so that first responders or emergency staff can administer cortisol replacement quickly if they’re found unconscious or in shock. Hospital admission rates for adrenal crisis related to secondary adrenal insufficiency have risen sharply in recent years, nearly doubling over a studied period, likely reflecting the growing number of people on long-term steroid therapy for chronic diseases.
Living With the Condition
Day to day, most people with well-managed secondary adrenal insufficiency lead normal lives. The adjustment involves taking medication consistently, learning to recognize early signs of cortisol insufficiency (unusual fatigue, nausea, light-headedness), and adjusting doses around illness or physical stress. Exercise, travel, and work are all possible with planning. Many people keep extra medication in multiple locations and inform close contacts about their condition in case of emergency.
Periodic check-ins with an endocrinologist help fine-tune dosing. Over-replacement can cause weight gain, bone thinning, and high blood sugar over time, so the goal is always the minimum dose that keeps symptoms at bay and prevents crisis. For those with steroid-induced suppression, repeat testing over time can determine whether the pituitary has recovered enough to stop replacement therapy entirely.