This is the part of ALD that is most easily missed and most dangerous when it is.
Cerebral disease and myelopathy progress over time. Adrenal insufficiency can threaten life within a day — and can be almost entirely prevented with preparation.
1. Why it matters
The adrenal glands sit above the kidneys and produce cortisol, the hormone that allows the body to respond to stress. In ALD, very long chain fatty acids accumulate in the adrenal cortex and that function fails.
Primary adrenal insufficiency is common in males with ALD. It is uncommon in women.
There is a further point. Adrenal insufficiency is sometimes the first manifestation of ALD, appearing years before any neurological sign. Boys and men diagnosed with primary adrenal insufficiency of no other established cause should therefore be tested for ALD.
Adrenal crisis
Day to day, a degree of insufficiency can be tolerated. But when infection, fever, surgery, injury or severe stress is added, it can decompensate abruptly. This is adrenal crisis.
Blood pressure falls, vomiting begins, consciousness clouds, and if treatment is delayed it can be fatal.
This is a preventable death. What usually goes wrong is that, at the moment it matters, nobody knows the patient has adrenal insufficiency.
2. How it presents
Onset is gradual, which makes it easy to miss.
Adults
- Profound, unexplained fatigue
- Loss of appetite, weight loss
- Dizziness, particularly on standing
- Nausea, vomiting, abdominal pain
- Darkening of the skin — gums, palmar creases, scars, nipples, skin folds
- Craving for salt
- Muscle and joint pain
Children
- Faltering growth
- Frequent vomiting, lethargy
- Hypoglycaemia, sometimes with seizures
- Darkening of the skin
Hyperpigmentation is easy to overlook but relatively characteristic. Families often describe it as looking tanned.
Presentations suggesting adrenal crisis
Adrenal crisis appears as:
- Profound lethargy, collapse
- Repeated vomiting, inability to keep fluids down
- Severe abdominal pain
- Dizziness with cold sweats, falling blood pressure
- Clouding of consciousness
Adrenal crisis is classified as a medical emergency, and outcomes worsen with delay. How quickly the treating team learns that the patient is on treatment for adrenal insufficiency governs how quickly they can act.
3. Testing — when and how often
From the international consensus recommendations.
Who — all boys and men, regardless of symptoms. Girls and women are not included in routine screening.
What — early morning cortisol and ACTH
Intervals
- Begin within the first six months of life
- Before age 10: every 3–6 months
- From age 10: yearly
- Performed alongside brain MRI where possible
- Continued into adult life irrespective of age, because the test is inexpensive and the benefit of early diagnosis is large
Mineralocorticoid deficiency is assessed alongside it, with plasma renin and serum electrolytes, both at screening and after a diagnosis is made.
Where symptoms suggest insufficiency, testing is done immediately rather than waiting for the schedule. In a patient already in crisis, a random cortisol and ACTH is sufficient — provided the sample is drawn before glucocorticoid is given.
4. Treatment
Glucocorticoid replacement is started under an endocrinologist. It replaces a hormone the body no longer makes, and is taken lifelong.
Mineralocorticoid replacement is not started on symptoms alone; plasma renin and serum electrolytes are taken into account.
Situations that place the body under load — infection, fever, surgery, injury — require a different approach from day-to-day management. What that approach is differs between patients, and is normally agreed with the treating clinicians in advance.
Based on the 2022 international consensus recommendations (Neurology). Sources are indicated in the text. Doses and individual management follow the instructions of the treating clinicians.
Last reviewed: 7 August 2026
This page provides general medical information and does not replace care for an individual patient.