Addison Disease
Basics
Description
- Primary adrenal gland insufficiency, which results from partial or complete (>90%) destruction of the adrenal cells with inadequate secretion of glucocorticoids and mineralocorticoids
- 80% of cases are caused by an autoimmune process, followed by tuberculosis (TB), AIDS, systemic fungal infections, and adrenoleukodystrophy.
- Addison disease (primary adrenocortical insufficiency) can be differentiated from secondary (pituitary failure) and tertiary (hypothalamic failure) causes because mineralocorticoids are intact in secondary and tertiary.
- Addisonian (adrenal) crisis: acute complication of adrenal insufficiency (circulatory collapse, dehydration, hypotension, nausea, vomiting, hypoglycemia); usually precipitated by an acute physiologic stressor(s) such as surgery, illness, exacerbation of comorbid process, and/or acute withdrawal of long-term corticosteroid therapy (defined as >3 months use of steroid)
- System(s) affected: endocrine/metabolic
- Synonym(s): adrenocortical insufficiency; corticoadrenal insufficiency; primary adrenocortical insufficiency
Epidemiology
- Predominant age: all ages; typical age of presentation is 30 to 50 years.
- Predominant sex: females and children > males (slight)
- No racial predilection
Incidence
0.6/100,000
Prevalence
40 to 60 cases in 1 million population
Etiology and Pathophysiology
- Autoimmune adrenal insufficiency (~80% in United States)
- Infectious causes: TB (most common cause worldwide), HIV (most common infectious cause in United States, often with concomitant infections such as cytomegalovirus), Waterhouse-Friderichsen syndrome (most commonly meningococcus), fungal disease
- Bilateral adrenal hemorrhage and infarction (for patients on anticoagulants)
- Antiphospholipid antibody syndrome
- Lymphoma, Kaposi sarcoma, metastasis (lung, breast, kidney, colon, melanoma); tumor must destroy 90% of gland to produce hypofunction.
- Drugs (e.g., ketoconazole, fluconazole, etomidate, methadone, mitotane, megestrol, medroxyprogesterone acetate, chronic opiate use, metyrapone, aminoglutethimide)
- Surgical adrenalectomy, radiation therapy
- Sarcoidosis, hemochromatosis, amyloidosis
- Congenital enzyme defects (deficiency of 21-hydroxylase enzyme is most common), neonatal adrenal hypoplasia, congenital adrenal hyperplasia, familial glucocorticoid insufficiency, autoimmune polyglandular autoimmune syndromes 1 and 2, adrenoleukodystrophy
- Idiopathic
- Abnormalities of β-oxidation of very long–chain fatty acids, most common cause of adrenal insufficiency in male child <7 years of age
- Destruction of the adrenal cortex resulting in deficiencies in cortisol, aldosterone, and androgens
Genetics
- Autoimmune polyglandular syndrome (APS) type 2 genetics are complex and are associated with adrenal insufficiency.
- APS type 1 is caused by mutations of the autoimmune regulator gene. Nearly all have the following triad: adrenal insufficiency, hypoparathyroidism, and mucocutaneous candidiasis before adulthood.
- Adrenoleukodystrophy is an X-linked recessive disorder resulting in toxic accumulation of unoxidized long-chain fatty acids.
- Increased risk with cytotoxic T-lymphocyte antigen 4 (CTLA-4)
Risk Factors
- 40% of patients have a first- or second-degree relative with associated disorders.
- Chronic steroid use, then experiencing severe infection, trauma, or surgical procedures
General Prevention
- Focus on prevention of complications. Anticipate adrenal crisis and treat before symptoms begin.
- Elective surgical procedures require upward adjustment in steroid dose.
Commonly Associated Conditions
- Diabetes mellitus
- Graves disease
- Hashimoto thyroiditis
- Hypoparathyroidism
- Hypercalcemia
- Ovarian failure
- Pernicious anemia
- Myasthenia gravis
- Vitiligo
- Chronic moniliasis
- Sarcoidosis
- Sjögren syndrome
- Chronic active hepatitis
- Schmidt syndrome
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Citation
Domino, Frank J., et al., editors. "Addison Disease." 5-Minute Clinical Consult, 34th ed., Wolters Kluwer, 2026. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116008/all/Addison_Disease.
Addison Disease. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2026. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116008/all/Addison_Disease. Accessed July 17, 2025.
Addison Disease. (2026). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (34th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116008/all/Addison_Disease
Addison Disease [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2026. [cited 2025 July 17]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116008/all/Addison_Disease.
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