Addison Disease

Basics

Primary adrenal gland insufficiency, which results from partial or complete (>90%) destruction of the adrenal cells with inadequate secretion of glucocorticoids and mineralocorticoids
80% of cases are caused by an autoimmune process, followed by tuberculosis (TB), AIDS, systemic fungal infections, and adrenoleukodystrophy.
Addison disease (primary adrenocortical insufficiency) can be differentiated from secondary (pituitary failure) and tertiary (hypothalamic failure) causes because mineralocorticoids are intact in secondary and tertiary.
Addisonian (adrenal) crisis: acute complication of adrenal insufficiency (circulatory collapse, dehydration, hypotension, nausea, vomiting, hypoglycemia); usually precipitated by an acute physiologic stressor(s) such as surgery, illness, exacerbation of comorbid process, and/or acute withdrawal of long-term corticosteroid therapy (defined as >3 months use of steroid)
System(s) affected: endocrine/metabolic
Synonym(s): adrenocortical insufficiency; corticoadrenal insufficiency; primary adrenocortical insufficiency

Incidence
0.6/100,000
Prevalence
40 to 60 cases in 1 million population

Autoimmune adrenal insufficiency (~80% in United States)
Infectious causes: TB (most common cause worldwide), HIV (most common infectious cause in United States, often with concomitant infections such as cytomegalovirus), Waterhouse-Friderichsen syndrome (most commonly meningococcus), fungal disease
Bilateral adrenal hemorrhage and infarction (for patients on anticoagulants)
Antiphospholipid antibody syndrome
Lymphoma, Kaposi sarcoma, metastasis (lung, breast, kidney, colon, melanoma); tumor must destroy 90% of gland to produce hypofunction.
Drugs (e.g., ketoconazole, fluconazole, etomidate, methadone, mitotane, megestrol, medroxyprogesterone acetate, chronic opiate use, metyrapone, aminoglutethimide)
Surgical adrenalectomy, radiation therapy
Sarcoidosis, hemochromatosis, amyloidosis
Congenital enzyme defects (deficiency of 21-hydroxylase enzyme is most common), neonatal adrenal hypoplasia, congenital adrenal hyperplasia, familial glucocorticoid insufficiency, autoimmune polyglandular autoimmune syndromes 1 and 2, adrenoleukodystrophy
Idiopathic
Abnormalities of β-oxidation of very long–chain fatty acids, most common cause of adrenal insufficiency in male child <7 years of age
Destruction of the adrenal cortex resulting in deficiencies in cortisol, aldosterone, and androgens

Genetics

Autoimmune polyglandular syndrome (APS) type 2 genetics are complex and are associated with adrenal insufficiency.
APS type 1 is caused by mutations of the autoimmune regulator gene. Nearly all have the following triad: adrenal insufficiency, hypoparathyroidism, and mucocutaneous candidiasis before adulthood.
Adrenoleukodystrophy is an X-linked recessive disorder resulting in toxic accumulation of unoxidized long-chain fatty acids.
Increased risk with cytotoxic T-lymphocyte antigen 4 (CTLA-4)

40% of patients have a first- or second-degree relative with associated disorders.
Chronic steroid use, then experiencing severe infection, trauma, or surgical procedures

Focus on prevention of complications. Anticipate adrenal crisis and treat before symptoms begin.
Elective surgical procedures require upward adjustment in steroid dose.

There's more to see -- the rest of this topic is available only to subscribers.