Addison's disease pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]


The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release corticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on the pituitary, which decreases the amount of ACTH released from the pituitary gland. When the adrenal glands do not produce enough cortisol and aldosterone, it results in Addison's disease.

Normal Physiology of Adrenal Glands

Hypothalamic–pituitary–adrenal axis

Source: By BrianMSweis (Own work) [CC BY-SA 3.0 (], via Wikimedia Commons


Harmone Type of class Function
Cortisol Glucocorticoids
Aldosterone Mineralocorticoids


Addison's disease occurs when the adrenal glands do not produce enough cortisol and, in some cases, aldosterone. Adrenal insufficiency may arise due to insufficient release of cortisol from the adrenal glands. Insufficient cortisol secretion may be due to adrenal dysgenesis (the gland does not form adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to the gland being damaged).[1][2][3]

Mechanism of adrenal insufficiency Definition Pathophysiology
Adrenal dysgenesis Gland does not form adequately during development
Impaired steroidogenesis
Adrenal destruction
  • Disease processes leading to the gland being damaged


Source: By A. Rad (me) (Own work) [GFDL ( or CC-BY-SA-3.0 (], via Wikimedia Commons

Associated conditions

Addison's disease is commonly seen associated with conditions such as:[6]


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  2. Nieman LK, Chanco Turner ML (2006). "Addison's disease". Clin. Dermatol. 24 (4): 276–80. doi:10.1016/j.clindermatol.2006.04.006. PMID 16828409.
  3. SMART GA (1953). "Addison's disease". Postgrad Med J. 29 (330): 200–7. PMC 2500363. PMID 13055541.
  4. Honour JW (2009). "Diagnosis of diseases of steroid hormone production, metabolism and action". J Clin Res Pediatr Endocrinol. 1 (5): 209–26. doi:10.4274/jcrpe.v1i5.209. PMC 3005746. PMID 21274298.
  5. Michels AW, Eisenbarth GS (2010). "Immunologic endocrine disorders". J. Allergy Clin. Immunol. 125 (2 Suppl 2): S226–37. doi:10.1016/j.jaci.2009.09.053. PMC 2835296. PMID 20176260.
  6. Zelissen PM, Bast EJ, Croughs RJ (1995). "Associated autoimmunity in Addison's disease". J. Autoimmun. 8 (1): 121–30. doi:10.1006/jaut.1995.0009. PMID 7734032.