Primary adrenal insufficiency
Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex, most often autoimmune, causing combined cortisol and aldosterone deficiency with hyperpigmentation, hyponatremia, and hyperkalemia. Lifelong glucocorticoid replacement with hydrocortisone plus mineralocorticoid replacement with fludrocortisone is required, with sick-day dose increases to prevent adrenal crisis.
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What this article covers
- Overview
Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex itself, producing combined deficiency of cortisol, aldosterone, and adrenal androgens, in contrast…
- Epidemiology
A rare, likely underdiagnosed disease, with autoimmune adrenalitis dominant in developed countries and tuberculous adrenalitis an important cause where tuberculosis burden is high.
- Risk factors
Personal or family history of autoimmune disease (thyroid disease, type 1 diabetes, primary ovarian insufficiency, hypoparathyroidism, vitiligo, celiac disease), reflecting shared susceptibility to polyglandular autoimmunity.
- Pathophysiology
Autoimmune destruction targets the adrenal cortex, with 21-hydroxylase, a key steroidogenic enzyme, as the principal autoantigen; progressive loss of cortical tissue leads to sequential loss of…
- Clinical features
Fatigue, weakness, and weight loss are near-universal but nonspecific, often present for months.
- Differential diagnosis
Secondary adrenal insufficiency: cortisol deficiency without aldosterone deficiency, so no hyperkalemia and no hyperpigmentation (ACTH is low, not high), distinguished by a low or inappropriately…
- Diagnosis
First, confirm cortisol deficiency biochemically: an 8 AM serum cortisol below roughly 3 mcg/dL (83 nmol/L) strongly indicates adrenal insufficiency; a value above 15-18 mcg/dL (414-497 nmol/L)…
- Management
First, initiate combined glucocorticoid and mineralocorticoid replacement, since both are required in primary disease: give hydrocortisone 15-25 mg PO daily divided into 2-3 doses, largest dose in…
- Complications
Adrenal crisis, the most dangerous complication, triggered by intercurrent illness, surgery, trauma, or missed sick-day dosing.
- Prognosis
With adequate lifelong replacement and sick-day education, life expectancy approaches the general population, though quality of life is often reported as reduced compared with unaffected peers.
- Prevention
Sick-day dose education for every patient: double to triple the usual hydrocortisone dose for 2-3 days during minor illness, escalating to parenteral treatment and emergency care if vomiting prevents oral intake.
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Related articles
- Adrenal crisis
Adrenal crisis is life-threatening acute glucocorticoid deficiency, most often precipitated by infection or another physiologic stress in a patient with known or unrecognized adrenal insufficiency, presenting with dehydration, hypotension, or shock out of proportion to the concurrent illness. Treatment is immediate intravenous hydrocortisone 100 mg followed by 50 mg every 6 hours plus isotonic saline with dextrose, without waiting for confirmatory labs.
- Secondary adrenal insufficiency
Secondary adrenal insufficiency is ACTH deficiency from pituitary or hypothalamic disease, or most commonly from withdrawal of prolonged exogenous glucocorticoid therapy, causing isolated cortisol deficiency without hyperpigmentation or hyperkalemia because aldosterone secretion is preserved. Lifelong glucocorticoid replacement with hydrocortisone, with dose increases during illness, prevents adrenal crisis.
- Autoimmune polyglandular syndrome 1
Autoimmune polyglandular syndrome type 1 (APS-1, also called APECED) is caused by mutation of the AIRE gene, which normally drives thymic negative selection against self-reactive T cells; loss of AIRE produces the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Management is component-specific and lifelong: fluconazole for candidiasis, calcium and calcitriol for hypoparathyroidism, and glucocorticoid plus mineralocorticoid replacement for adrenal insufficiency, with structured lifelong screening for additional autoimmune endocrinopathies as they emerge.
- Autoimmune polyglandular syndrome 2
Autoimmune polyglandular syndrome type 2 (APS-2, or Schmidt syndrome) is the co-occurrence of autoimmune primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes, plus often primary ovarian insufficiency, pernicious anemia, celiac disease, or vitiligo, over a patient's lifetime. Management is component-specific hormone replacement, with adrenal insufficiency treated first because untreated hypothyroidism can mask it and starting levothyroxine before glucocorticoid replacement can precipitate adrenal crisis.