Addison's disease
Also known as: primary adrenal insufficiency
Medically reviewed by Hormone Journal Editorial Team · Last reviewed 2026-05-22
Addison's disease is a rare condition affecting roughly 1 in 10,000 people in which the adrenal glands permanently cannot produce enough cortisol and aldosterone.
What it is
Addison's disease is a rare condition affecting approximately 1 in 10,000 people in which the adrenal glands permanently lose the ability to produce adequate cortisol and aldosterone. Also called primary adrenal insufficiency, it is distinct from secondary and tertiary adrenal insufficiency, which originate in the pituitary gland and hypothalamus respectively. The adrenal glands — two small glands that sit above the kidneys — produce cortisol (essential for stress response, metabolism, and immune function) and aldosterone (which regulates sodium, potassium, and blood pressure). When both hormones fall below functional levels, the effects touch nearly every organ system. Addison's disease is most commonly diagnosed between ages 30 and 50 and is slightly more prevalent in women than men. In Canada, diagnosis and ongoing management typically involve an endocrinologist, with cortisol testing available through national laboratory networks including LifeLabs and Dynacare.
The condition is lifelong, but with consistent hormone replacement most people manage it well and live full, active lives. The primary clinical challenge is early recognition: symptoms accumulate gradually and are frequently attributed to chronic fatigue, depression, or anxiety before the correct diagnosis is made.
Causes and mechanism
Autoimmune adrenalitis accounts for 70–90% of cases in developed countries, including Canada. The immune system progressively destroys the adrenal cortex — the outer layer responsible for cortisol and aldosterone synthesis — until hormone output falls below the threshold needed to sustain normal function.
Other causes include:
| Cause | Notes |
|---|---|
| Tuberculosis | Leading cause globally; less common in Canada but relevant in high-risk populations |
| Fungal infections | Histoplasmosis, coccidioidomycosis — can infiltrate adrenal tissue |
| Metastatic cancer | Lung, breast, and other cancers can spread to the adrenal glands |
| Adrenal hemorrhage | Severe infection, trauma, or clotting disorders can cause bilateral bleeding |
| Surgical removal | Bilateral adrenalectomy produces immediate adrenal insufficiency |
People with other autoimmune conditions — type 1 diabetes, Hashimoto's thyroiditis, vitiligo — carry a modestly elevated risk. Addison's disease can also appear as part of autoimmune polyendocrine syndrome, a rare inherited cluster of autoimmune endocrine disorders.
Symptoms and diagnosis
Symptoms develop slowly, often over months, and are non-specific in early stages. The most recognizable features are:
- Persistent fatigue and muscle weakness unrelieved by rest
- Unintentional weight loss and reduced appetite
- Postural hypotension — dizziness or fainting when standing
- Nausea, vomiting, or diarrhea
- Strong salt cravings
- Hypoglycemia (low blood sugar)
- Low mood, irritability, or depression
- Hyperpigmentation — darkening of skin folds, scars, and pressure points such as elbows and knuckles; this sign may be subtler on darker skin tones
Adrenal crisis is a medical emergency. It presents as sudden severe abdominal or back pain, extreme weakness, very low blood pressure, vomiting, and confusion, typically triggered by illness, injury, or surgery. Without prompt treatment it can be fatal.
Diagnostic workup follows a stepwise approach:
- Morning serum cortisol — a low result raises suspicion
- ACTH stimulation test — the gold standard; a blunted cortisol response after synthetic ACTH confirms adrenal insufficiency
- Plasma ACTH level — elevated ACTH with low cortisol confirms primary (adrenal) rather than secondary (pituitary) disease
- Adrenal autoantibodies — positive in autoimmune cases
- Electrolytes — typically low sodium and elevated potassium
- CT or MRI of the adrenal glands — to identify structural causes
Treatment options
Treatment replaces the hormones the adrenal glands can no longer produce and is lifelong.
Glucocorticoid replacement: Hydrocortisone is the preferred agent, taken orally two or three times daily to approximate the body's natural cortisol rhythm. Prednisone or dexamethasone are used as alternatives in some patients.
Mineralocorticoid replacement: Fludrocortisone, taken once daily, replaces aldosterone and helps the kidneys retain sodium, maintain blood pressure, and regulate fluid balance.
Stress dosing (sick day rules): During physical stress — fever, infection, vomiting, surgery, or serious injury — the hydrocortisone dose must be temporarily doubled or tripled. Failure to do so is the most common precipitant of an adrenal crisis. All patients should receive clear written instructions on sick day management.
Emergency hydrocortisone kit: Patients are advised to carry injectable hydrocortisone for situations where oral medication cannot be absorbed due to vomiting or loss of consciousness. In Canada, this typically requires a prescription and patient or caregiver training in self-injection.
DHEA supplementation: Sometimes considered for women with Addison's disease who experience ongoing fatigue, low mood, or reduced libido despite adequate cortisol and aldosterone replacement, though evidence for routine use remains limited.
Medical alert identification: Wearing a medical alert bracelet or carrying a wallet card is strongly recommended so emergency clinicians can administer hydrocortisone without delay.
When to see a clinician in Canada
Consult a physician if you have any of the following without a clear explanation: persistent fatigue or muscle weakness lasting several weeks, gradual unintentional weight loss, skin darkening in palm creases or over scars, dizziness when standing, an unusual craving for salty foods, or recurrent nausea alongside unexplained tiredness. A family physician can order initial cortisol and electrolyte testing; referral to an endocrinologist is appropriate if results are abnormal or suspicion remains high.
Call 911 or go to the nearest emergency department immediately if you develop sudden severe abdominal or back pain, extreme weakness, very low blood pressure, vomiting, or confusion — especially during or after an illness or injury. These are signs of an adrenal crisis.
Canadians managing Addison's disease long-term should confirm whether fludrocortisone and hydrocortisone are covered under their provincial drug benefit plan, as formulary listings vary by province. Virtual care platforms (Maple, Felix, Cleo, Phoenix, and others) can support routine follow-up but are not a substitute for specialist oversight of this condition.
Limitations and open questions
Research is still emerging on optimal hydrocortisone dosing schedules, including whether modified-release formulations that better mimic the natural cortisol curve improve quality of life over standard immediate-release regimens. Evidence for routine DHEA supplementation is mixed, and Health Canada has not issued specific guidance on its use in adrenal insufficiency. The long-term cardiovascular and bone-density effects of lifelong glucocorticoid replacement — even at physiologic doses — are not fully characterized. Diagnostic delays remain a documented problem: studies suggest the average time from symptom onset to confirmed diagnosis can exceed two years, and Canadian-specific data on diagnostic lag are limited. Patients from communities with higher tuberculosis prevalence may face different underlying cause profiles, but Canadian epidemiological data on this are sparse.
FAQs
What is the difference between Addison's disease and adrenal fatigue?
Addison's disease is a medically confirmed condition in which the adrenal glands are structurally damaged and cannot produce enough cortisol or aldosterone — verified by blood tests including the ACTH stimulation test and treated with lifelong hormone replacement. Adrenal fatigue is not a recognized medical diagnosis; it is an informal term applied to tiredness and stress-related symptoms in the absence of measurable hormone deficiency or adrenal damage. If you have persistent, unexplained fatigue, a proper workup — including a morning cortisol level — is the right first step rather than assuming either label.
Can people with Addison's disease live a normal life?
Yes. With consistent hormone replacement, most people with Addison's disease live full, active lives. The key practical skills are knowing when to increase the hydrocortisone dose during illness (typically doubling or tripling it at the first sign of fever or infection), always having an emergency injectable hydrocortisone kit available, and attending regular endocrinology follow-up to keep dosing well-calibrated. Studies suggest that with good management, life expectancy approaches that of the general population, though quality-of-life impairment from fatigue and mood symptoms is reported by a meaningful proportion of patients even on treatment.
What triggers an adrenal crisis and how can it be prevented?
An adrenal crisis occurs when the body faces significant physical stress — fever, infection, surgery, or serious injury — and cannot produce the surge of cortisol that stress demands. Prevention relies on four practices: following sick day rules (doubling or tripling the hydrocortisone dose at the first sign of illness), seeking emergency care promptly if vomiting prevents oral medication from being absorbed, carrying a prescribed injectable hydrocortisone kit, and wearing a medical alert bracelet so any treating clinician knows to administer hydrocortisone immediately. Without treatment, an adrenal crisis can be fatal within hours.
Is Addison's disease hereditary?
Addison's disease itself is not directly inherited, but a predisposition to autoimmune conditions — the underlying cause in 70–90% of cases in countries like Canada — can run in families. People with a first-degree relative who has type 1 diabetes, Hashimoto's thyroiditis, or another autoimmune disease have a modestly higher likelihood of developing adrenal autoimmunity. A rare inherited condition called autoimmune polyendocrine syndrome is associated with higher rates of adrenal insufficiency alongside other endocrine disorders, and genetic testing may be appropriate in those cases.
Are the medications for Addison's disease covered by provincial drug plans in Canada?
Coverage varies by province. Hydrocortisone and fludrocortisone — the two core replacement medications — are listed on most provincial formularies, but patients should confirm their specific plan's coverage, tier, and any prior-authorization requirements. Patients on provincial social assistance programs or federal Non-Insured Health Benefits (for eligible First Nations and Inuit individuals) should verify coverage directly with their benefits administrator. Out-of-pocket costs for the emergency injectable hydrocortisone kit can also vary, so discussing this with a pharmacist or endocrinologist is worthwhile.
Sources
- Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline
- Adrenal insufficiency — StatPearls, NCBI Bookshelf (NIH)
- Adrenal Insufficiency & Addison's Disease — NIDDK, National Institutes of Health
- Addison's Disease — Symptoms and Causes, Mayo Clinic
- Adrenal insufficiency — The Lancet (Charmandari et al., 2014)
- Consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency — Journal of Internal Medicine (Husebye et al., 2014)