Addison's Disease: Symptoms, Causes, Diagnosis & Treatment

Primary vs Secondary Adrenal Insufficiency

Addison's disease specifically refers to primary adrenal insufficiency -- the adrenal glands themselves are damaged and can't produce cortisol, regardless of how much ACTH (the pituitary hormone that signals the adrenals to make cortisol) is telling them to. In the US and other developed countries, the most common cause is autoimmune destruction of the adrenal cortex, accounting for a majority of cases; worldwide, infections such as tuberculosis remain a significant cause. Because aldosterone (which regulates sodium and potassium) is also made by the adrenal cortex, primary adrenal insufficiency typically affects both hormones.

Secondary adrenal insufficiency is a different problem -- the adrenal glands themselves are fine, but the pituitary gland isn't producing enough ACTH to signal them (from a pituitary tumor, prior pituitary surgery/radiation, or most commonly from long-term glucocorticoid medication use suppressing the body's own ACTH production). Aldosterone is usually preserved in secondary adrenal insufficiency because its regulation doesn't depend heavily on ACTH. The distinction matters for both diagnosis (which lab pattern to expect) and treatment (secondary cases from medication use often improve once the medication is tapered under medical supervision, whereas Addison's disease itself is permanent).

Symptoms

• Chronic fatigue and muscle weakness -- often the earliest and most persistent complaint
• Unintentional weight loss and reduced appetite
• Low blood pressure, including a drop when standing up (orthostatic hypotension), sometimes causing dizziness or fainting
• Salt cravings -- a relatively specific clue, from aldosterone deficiency causing sodium loss
• Hyperpigmentation -- darkening of the skin, especially in skin folds, scars, and gums; happens only in primary adrenal insufficiency because the same precursor molecule that makes excess ACTH also stimulates melanin production. This is a genuinely useful clue that distinguishes Addison's from the secondary form, where it does not occur.
• Nausea, vomiting, or abdominal pain
• Low blood sugar (hypoglycemia)
• Irritability or depression

These symptoms typically develop gradually over months, which is part of why Addison's disease is often diagnosed late -- fatigue and weight loss get attributed to stress or other causes before the pattern is recognized as adrenal in origin.

How It's Diagnosed

An AM serum cortisol below roughly 3 μg/dL is strongly suggestive of adrenal insufficiency, while a result above 18 μg/dL effectively rules it out. Most results fall in between, which is where the ACTH stimulation test becomes the definitive diagnostic step: synthetic ACTH is administered, and cortisol is measured before and 30-60 minutes after. A normal adrenal gland responds by raising cortisol above roughly 18 μg/dL; in Addison's disease, the damaged adrenal cannot respond adequately, and cortisol stays low. A baseline ACTH level helps distinguish primary from secondary insufficiency -- ACTH is high in Addison's disease (the pituitary is trying harder to stimulate a gland that can't respond) and low or inappropriately normal in secondary insufficiency. Additional testing (21-hydroxylase antibodies, imaging, or TB testing, such as a QuantiFERON-TB Gold test, depending on risk factors) helps identify the underlying cause. For the full reference-range table across serum, salivary, and urinary cortisol testing, see our cortisol levels guide. For how adrenal insufficiency fits alongside other conditions' own diagnostic workups, see our lab tests for common conditions guide.

Treatment: Lifelong Hormone Replacement

Addison's disease is managed, not cured, with daily glucocorticoid replacement -- typically hydrocortisone, prednisone, or dexamethasone -- dosed to mimic the body's natural cortisol rhythm as closely as possible (usually a larger dose in the morning, smaller in the afternoon). Most people also need a mineralocorticoid (fludrocortisone) to replace aldosterone and maintain normal sodium/potassium balance and blood pressure.

A critical part of long-term management is sick-day dosing -- during illness, injury, surgery, or significant physical stress, the body would normally produce several times its baseline cortisol, and someone with Addison's disease cannot do that on their own. Standard management includes doubling or tripling the glucocorticoid dose temporarily during these periods, under guidance already established with their endocrinologist, to prevent a crisis.

Addison's Disease vs Cushing's Syndrome at a Glance

Addison's disease and Cushing's syndrome are the two opposite failure modes of the same cortisol system -- one is too little, the other is too much -- which is why they get compared directly so often. The table below lines up the key differences side by side.

The verdict: these are opposite conditions, never a differential diagnosis toss-up. A patient's symptom direction -- weight loss and low blood pressure versus weight gain and high blood pressure -- almost always points clearly toward one or the other before testing even starts; lab confirmation (ACTH stimulation vs dexamethasone suppression) then settles it. See our Cushing's syndrome guide for the full picture of the high-cortisol side.

Adrenal Crisis: A Medical Emergency

An adrenal crisis is a sudden, severe worsening of adrenal insufficiency -- a life-threatening emergency, not a symptom to manage at home. It's usually triggered by an illness, injury, surgery, or missed medication doses in someone with existing (diagnosed or undiagnosed) adrenal insufficiency. Recognized by: severe weakness, vomiting, very low blood pressure, confusion, and in severe cases loss of consciousness. Anyone with known adrenal insufficiency who develops these symptoms -- particularly during illness or major stress -- needs emergency medical care immediately, not a wait-and-see approach. People with confirmed Addison's disease are typically prescribed an emergency injectable hydrocortisone kit and are advised to wear medical-alert identification for exactly this reason.