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Addison’s Disease

Addison’s Disease is primary adrenal insufficiency caused by destruction or dysfunction of the adrenal cortex, resulting in inadequate production of cortisol and aldosterone.

Also called

Primary Adrenal Insufficiency

ICD-10

D35.2

Specialty

Endocrine

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

  • Addison’s Disease occurs when the adrenal cortex cannot produce sufficient glucocorticoids and mineralocorticoids.

 

  • The most common cause in many settings is autoimmune adrenalitis. Other causes include tuberculosis, adrenal hemorrhage, metastatic disease, and certain infections.

-Typical features include:

  • Fatigue
  • Weight loss
  • Hyperpigmentation
  • Hypotension
  • Hyponatremia
  • Hyperkalemia
  • Hypoglycemia

Etiology & Risk Factors

–Etiology of Addison’s Disease:

-Autoimmune

The most common cause of Addison’s Disease in developed countries is autoimmune destruction of the adrenal cortex.

Autoantibodies against 21-hydroxylase are commonly present.

-Infectious

  • Tuberculosis
  • HIV-associated infections

-Other Causes

  • Bilateral adrenal hemorrhage
  • Adrenal metastases
  • Adrenal infiltration
  • Adrenalectomy

 

-Risk Factors for Addison’s Disease:

  • Autoimmune disease
  • Family history of autoimmune disease
  • Previous tuberculosis
  • HIV infection
  • Adrenal surgery
  • Adrenal hemorrhage
  • Metastatic malignancy

Pathophysiology

Adrenal cortex destruction → ↓ cortisol + ↓ aldosterone → ↓ cortisol-mediated glucose regulation + ↓ vascular responsiveness + renal sodium loss → hypotension + hyponatremia + dehydration + hyperkalemia → ↑ ACTH due to loss of negative feedback → increased melanocortin activity → hyperpigmentation

Clinical Presentation

-Symptoms:

  • Fatigue
  • Generalized weakness
  • Weight loss
  • Loss of appetite
  • Nausea
  • Vomiting
  • Abdominal pain
  • Diarrhea
  • Salt craving

-Signs:

  • Hyperpigmentation
  • Hypotension
  • Vitiligo in autoimmune disease
  • Darkening of palmar creases
  • Darkening of scars
  • Pigmentation of oral mucosa

History Taking

-Ask about:

  • Fatigue and weakness
  • Weight loss
  • Appetite
  • Nausea and vomiting
  • Abdominal pain
  • Diarrhea
  • Salt craving
  • Dizziness
  • Postural symptoms
  • Episodes of fainting
  • Hyperpigmentation
  • Hypoglycemic symptoms

Physical Examination

-General Examination:

  • Weight
  • Blood pressure
  • Orthostatic blood pressure
  • Heart rate

-Look for:

  • Weight loss
  • Dehydration
  • Hyperpigmentation


-System-Specific Examination:

–Skin

Look for:

  • Generalized hyperpigmentation
  • Palmar crease pigmentation
  • Knuckle pigmentation
  • Scar pigmentation

 

–Endocrine

  • Assess for evidence of other autoimmune endocrine diseases, particularly:
  • Thyroid disease
  • Type 1 Diabetes Mellitus

Investigations

-Biochemistry / Specific Tests:

  • Typical findings include:
  • Low serum sodium
  • High serum potassium
  • Low glucose in some patients
  • Increased urea
  • Increased creatinine during dehydration
  • Low serum bicarbonate in severe cases

 

-Serum Cortisol:

  • A low morning serum cortisol strongly supports adrenal insufficiency.
  • ACTH
  • High ACTH → primary adrenal insufficiency
  • Low or inappropriately normal ACTH → suggests secondary/tertiary adrenal insufficiency

 

-Special / Confirmatory Tests:

-ACTH Stimulation Test

The 250-µg cosyntropin stimulation test is commonly used to confirm adrenal insufficiency.

In primary adrenal insufficiency:

ACTH administration → inadequate rise in serum cortisol

-Adrenal Autoantibodies

21-hydroxylase antibodies support an autoimmune cause

Diagnosis

Diagnosis of Addison’s Disease  is established by demonstrating inadequate cortisol production and determining whether the problem is primary or central.

-Typical findings in Addison Disease:

  • Low morning cortisol
  • High ACTH
  • Inadequate cortisol response to ACTH stimulation
  • Low aldosterone
  • High renin
  • Hyponatremia
  • Hyperkalemia
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Management

1. First-Line / Emergency Management

Suspected Addisonian Crisis

Immediate treatment:

  • IV hydrocortisone
  • Rapid intravenous isotonic fluid replacement
  • Correction of hypoglycemia
  • Electrolyte monitoring
  • Treatment of the precipitating cause

Common precipitants include:

  • Infection
  • Surgery
  • Trauma
  • Vomiting or inability to take medication

 

2. Definitive Treatment

Lifelong hormone replacement is usually required.

The goals are:

  • Replace cortisol
  • Replace aldosterone
  • Prevent adrenal crisis
  • Educate the patient about stress dosing

3. Medical Treatment

Glucocorticoid Replacement

Common options include:

  • Hydrocortisone
  • Prednisolone

Hydrocortisone is commonly used because its pharmacological profile resembles physiological cortisol secretion.

 

4. Supportive Management

  • Patient education
  • Stress-dose steroid instructions
  • Medical alert identification
  • Emergency injectable hydrocortisone when appropriate

Complications

  • Addisonian crisis
  • Hypotension
  • Shock
  • Severe dehydration
  • Hyponatremia
  • Hyperkalemia
  • Hypoglycemia
  • Acute kidney injury
  • Cardiac arrhythmias due to severe electrolyte abnormalities

Prognosis

–With appropriate lifelong hormone replacement and patient education, the prognosis is generally good.

-The major life-threatening complication is adrenal crisis, which can occur when glucocorticoid requirements increase and replacement is inadequate.

-Prognosis is improved by:

  • Correct diagnosis
  • Adequate hormone replacement
  • Proper stress dosing
  • Emergency steroid access
  • Patient education

Key Points / Clinical Pearls

  • Addison’s Disease is primary adrenal insufficiency caused by failure of the adrenal cortex.
  • It causes ↓ cortisol and usually ↓ aldosterone.
  • Autoimmune adrenalitis is the most common cause in many settings.
  • Classic features include fatigue, weight loss, hypotension, and hyperpigmentation.
  • Salt craving may occur due to mineralocorticoid deficiency.
  • Typical laboratory findings are hyponatremia, hyperkalemia, and sometimes hypoglycemia.
  • Low cortisol + high ACTH suggests primary adrenal insufficiency.
  • High renin + low aldosterone indicates mineralocorticoid deficiency.
  • 21-hydroxylase antibodies support an autoimmune cause.
  • The ACTH stimulation test is commonly used to confirm adrenal insufficiency.
  • Hyperpigmentation helps distinguish primary from secondary adrenal insufficiency.
  • Treatment requires lifelong glucocorticoid replacement
  •  
  • Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. Journal of Clinical Endocrinology & Metabolism .
  • Husebye ES, Pearce SH, Krone NP, Kämpe O. Adrenal Insufficiency. Lancet. 2021;397(10274):613-629. The Lancet .
  • Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction. Endocr Rev. 2002;23(3):327-364.
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Addison's Disease . National Institutes of Health.
  • National Library of Medicine (NIH). Addison Disease . StatPearls.