What are normal and stress production of endogenous corticocosteroids?
What are the types of adrenal insufficiency?
Which patients are at high risk 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, 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 life-saving 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 40–110 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 150–280 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 151-1).
Table Graphic Jump Location Table 151-1 Primary, Secondary, and Tertiary Adrenal Insufficiency ||Download (.pdf)
Table 151-1 Primary, Secondary, and Tertiary Adrenal Insufficiency
- 40–110 cases/million
- 6 cases/million/year
- > 90% of destruction of adrenal cortex
- Loss of mineralocorticoid and glucocorticoid production
- Patients may be hyperpigmented
- Requires lifetime therapy
- ˜80% of cases in 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
- 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
- Infiltrative diseases
- Head trauma
- Intracranial artery aneurysms
- Sheehan syndrome
- 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