Key Clinical Questions
What are the types of adrenal insufficiency?
What are normal and stress production levels of endogenous corticocosteroids?
Which patients are at high risk for development of adrenal insufficiency or critical illness-related corticosteroid insufficiency and therefore may benefit from physiologic or pharmacologic steroid treatment of their illnesses?
For those patients who need corticosteroid supplementation, which agents should be used, at what dose and for how long?
Adrenal insufficiency (AI) was described by Thomas Addison in 1855 as a fatal disease caused by tuberculous adrenalitis and adrenal gland failure. In 1949, the synthesis of cortisone resulted in lifesaving therapy for Addison disease. However, this was shortly followed by reports of patient deaths from presumed adrenal crisis due to abrupt cortisone withdrawal in the perioperative period. These reports resulted in a new standard of administration of high doses of supplemental corticosteroids during periods of physical stress, although this practice may not be universally warranted.
Primary AI (Addison disease) refers to primary adrenal gland dysfunction. It has a prevalence of 40 to 110 cases per million people and an incidence of six cases per million people per year. Secondary AI denotes pituitary disease with adrenocorticotropic hormone (ACTH) hormone deficiency. The prevalence of secondary AI is approximately 150 to 280 per million. Hypothalamic dysfunction is responsible for tertiary AI. It usually arises after abrupt withdrawal or reduction in corticocosteroid dose, in the setting of chronic exogenous corticosteroids, and is reasonably common in the hospital setting, although the exact prevalence is unknown (Table 153-1).
TABLE 153-1Primary, Secondary, and Tertiary Adrenal Insufficiency ||Download (.pdf) TABLE 153-1 Primary, Secondary, and Tertiary Adrenal Insufficiency
|Type ||Incidence ||Features ||Etiologies |
|Primary || |
>90% of destruction of adrenal cortex
Loss of mineralocorticoid and glucocorticoid production
Patients may be hyperpigmented
Requires lifetime therapy
~80% of cases in the United States
Isolated autoimmune adrenalitis
APS-1—associated with hypoparathyroidism, chronic mucocutaneous candidiasis
APS-2—associated with thyroid disease, type 1 diabetes mellitus
AIDS—CMV, MAC, Kaposi sarcoma
30% of patients with AIDS develop AI
Fungal infections (histoplasmosis, coccidiomycosis, blastomycosis)
Metastases from breast, lung, and melanoma may infiltrate and replace normal adrenal tissue
Acute Addisonian crisis
Infectious—meningococcemia with purpura fulminans (Waterhouse-Friederichsen syndrome); sepsis with other bacteria
Drug-induced adrenal insufficiency
Mitotane, ketoconazole, suramin, etomidate, aminoglutethimide
|Secondary || |
150-280 per million
Pituitary disease that interferes with ACTH secretion
Clinical features due to loss of glucocorticoid function
Intact mineralocorticoid function
Rarely hypovolemic, more commonly hypoglycemic
Pituitary tumors, craniopharyngomas
Intracranial artery aneurysms
Isolated ACTH deficiency
Rare, likely autoimmune process
|Tertiary ||Most common form ||Processes that interfere with hypothalamic CRH secretion || |
Abrupt cessation of glucocorticoid therapy
Correction of Cushing syndrome