Practice Essentials
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.
Prognosis
With proper control, the long-term prognosis is good. Overall mortality rate is normal in treated patients. See Prognosis.
Patient education
Advise patients to wear medical alert tags at all times to reduce the time to the treatment and diagnosis of an addisonian crisis. Inform patients about salt loss during vigorous exercise.
Diagnostics
See Workup.
Treatment
See Medical Care, Long-Term Monitoring, and Medication.
Advise patients not to restrict salt in their diets. In patients with concurrent primary hypertension, salt intake may be restricted instead of discontinuing mineralocorticoid replacement. Advise patients who live in warm climates to increase their salt intake because of their increased loss of salt as a result of sweating.
No restrictions on activity are required; however, inform patients about salt loss during vigorous exercise.
Pay attention to potential drug interactions. Concomitant use of rifampin, phenytoin, or barbiturates increases the metabolism of replaced hormones; therefore, the patient's hormone levels may decrease to subtherapeutic levels.
Excessive sodium loss may result from the use of diuretics.
The need for consultation depends on the cause of the adrenal insufficiency and may involve the following specialists:
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Endocrinologist
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Rheumatologist
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Infectious diseases specialist
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.
Epidemiology
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. 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.
Prognosis
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. One 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.
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Hyperpigmented scar on diffusely hyperpigmented (tanned) skin. Courtesy of Dirk M. Elston, MD.
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Hyperpigmented scars from ear piercing. Courtesy of Dirk M. Elston, MD.
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Pigmented patches of mucous membrane and pigmented longitudinal nail bands. Courtesy of Dirk M. Elston, MD.
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Hyperpigmented gingival patches. Courtesy of Dirk M. Elston, MD.
