Addison Disease 

  • Author: Elizabeth A Liotta, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jun 7, 2010
 

Background

In 1855, Thomas Addison first described adrenal insufficiency, which was subsequently named after him. The basis of Addison disease has dramatically changed since its initial description. Originally, the disease usually resulted from an infection of the adrenal gland; the most common infection was tuberculosis, which is still the predominant cause of Addison disease in developing countries. Currently, in developed countries, Addison disease most commonly results from nonspecific autoimmune destruction of the adrenal gland.

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Pathophysiology

Adrenal insufficiency can manifest as a defect anywhere in the hypothalamic-pituitary-adrenal axis. Primary adrenal insufficiency is a result of destruction of the adrenal cortex. The zona glomerulosa, the outer layer of the adrenal gland, produces aldosterone. Cortisol is produced in both the zona fasciculata and the zona reticularis, the middle and innermost layers of the adrenal gland, respectively. Dehydroepiandrosterone is produced in the zona reticularis.

Clinical findings are noted after 90% of the adrenal cortex has been destroyed. Precipitating events are multifactorial and include autoimmune, infectious (eg, mycobacterial, fungal), neoplastic (eg, primary, metastatic), traumatic, iatrogenic (eg, surgery, medication), vascular (eg, hemorrhage, emboli, thrombus), and metabolic (eg, amyloidosis) events. With the destruction of the adrenal cortex, feedback inhibition of the hypothalamus and anterior pituitary gland is interrupted, and corticotropin is secreted continuously. Corticotropin and melanocyte-stimulating hormone (MSH) are both components of the same progenitor hormone. When corticotropin is cleaved from the prohormone, MSH is concurrently released. The increased MSH level results in a characteristic bronze hyperpigmentation. Hyperpigmentation is generally noted in primary adrenal insufficiency associated with increased levels of corticotropin and MSH.

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Epidemiology

Frequency

United States

The reported incidence of Addison disease is 5 or 6 cases per million population per year, with a prevalence of 60-110 cases per million population.

Mortality/Morbidity

The mortality rate for Addison disease is 1.4 deaths per million cases per year. This estimate is outdated because the incidence of tuberculosis-related Addison disease was greater when these data were compiled than it is now. A Swedish study reported that the relative rate of death in Addison disease patients was 2-fold higher than in background patients.[1] Malignancy, infectious diseases, and cardiovascular events were the responsible causes of this higher mortality rate. Diabetes mellitus was noted in 12% of this population, but it contributed only a small amount to the overall higher mortality rate.

Sex

The male-to-female ratio is 1:1.5-3.5.

Age

Addison disease can occur in persons of any age; however, it is most common in people aged 30-50 years. The expression of adrenal cortex antibodies (ACAs) in patients without symptoms of Addison disease represents a significant risk of progression to adrenal insufficiency. The risk varies with age; children have a high risk of progression compared with adults, in whom the expression of ACAs represents a 30% risk of progression to Addison disease.

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Contributor Information and Disclosures
Author

Elizabeth A Liotta, MD  Assistant Professor, Department of Dermatology, Uniformed Services University of the Health Sciences

Elizabeth A Liotta, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Alexander Brough, MD  Consulting Surgeon, Department of Dermatology, Sewell's Point Clinic

Alexander Brough, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Robin Travers, MD  Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians

Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Medical Dermatology Society, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD  Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Medicis Honoraria Consulting; Celgene Honoraria Consulting

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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Hyperpigmented scar on diffusely hyperpigmented (tanned) skin. Courtesy of Dirk M. Elston, MD.
Hyperpigmented scars from ear piercing. Courtesy of Dirk M. Elston, MD.
Pigmented patches of mucous membrane and pigmented longitudinal nail bands. Courtesy of Dirk M. Elston, MD.
Hyperpigmented gingival patches. Courtesy of Dirk M. Elston, MD.
 
 
 
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