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.
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What this article covers
- Overview
Secondary adrenal insufficiency is cortisol deficiency from inadequate adrenocorticotropic hormone (ACTH) secretion, not from disease of the adrenal gland itself, so aldosterone production is…
- Epidemiology
Iatrogenic suppression from exogenous glucocorticoids is the most common cause, typically following withdrawal after more than 3 weeks of pharmacologic-dose use (more than roughly 5 mg prednisone or equivalent per day).
- Risk factors
Prolonged pharmacologic glucocorticoid therapy (oral, and sometimes inhaled, intra-articular, or topical), especially when used more than 3 weeks and stopped abruptly.
- Pathophysiology
Loss of corticotroph function or hypothalamic corticotropin-releasing hormone drives the ACTH deficiency, from tumor compression, infarction, hemorrhage, surgery, radiation, autoimmune destruction, or exogenous glucocorticoid suppression.
- Clinical features
Fatigue, weight loss, nausea, and dizziness are the dominant nonspecific symptoms.
- Differential diagnosis
Primary adrenal insufficiency: hyperpigmentation, hyperkalemia, and orthostatic hypotension are present because both cortisol and aldosterone are lost and ACTH is elevated, unlike the isolated cortisol deficiency of secondary disease.
- Diagnosis
First, confirm cortisol deficiency biochemically: a morning (8 AM) cortisol below roughly 3 mcg/dL (83 nmol/L) strongly suggests deficiency, while a value above 15-18 mcg/dL (414-497 nmol/L) makes it…
- Management
First, replace glucocorticoid alone: give hydrocortisone 15-20 mg PO daily in two divided doses as standard chronic replacement; mineralocorticoid replacement is not needed in secondary disease…
- Complications
Adrenal crisis, precipitated by intercurrent illness, surgery, or abrupt glucocorticoid withdrawal, though frank hypotensive shock is less common than in primary disease because aldosterone is preserved.
- Prognosis
With appropriate glucocorticoid replacement and sick-day education, outcomes are generally favorable, and the lower risk of hyperkalemia and severe hypotension makes crisis somewhat less common than in primary disease.
- Prevention
Taper, do not abruptly stop, glucocorticoid therapy used at pharmacologic doses for more than 3 weeks, to allow gradual axis recovery and avoid precipitating insufficiency.
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- 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.
- Adrenal crisis
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