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Assess for adrenal insufficiency using morning cortisol, ACTH stimulation test results, and clinical symptoms. Get stress dosing guidance for confirmed cases.
Screening Tests
Start with morning cortisol for screening. If < 3 mcg/dL, AI is likely; if ≥ 18 mcg/dL, AI is unlikely; if 3-18 mcg/dL, ACTH stimulation test is needed.
< 3: AI likely | 3-18: Testing needed | ≥ 18: AI unlikely
High ACTH (> 60) with low cortisol = Primary AI | Low ACTH = Secondary AI
250 mcg cosyntropin given IV or IM. Cortisol measured at baseline, 30 min, and 60 min. Peak cortisol ≥ 18-20 mcg/dL is normal.
Note: Hyperpigmentation suggests primary AI (high ACTH stimulates melanocytes)
Adrenal insufficiency (AI) occurs when the adrenal glands fail to produce adequate amounts of cortisol and, in primary AI, aldosterone. It can be life-threatening if unrecognized or inadequately treated, particularly during physiological stress.
Primary Adrenal Insufficiency (Addison Disease): Destruction of the adrenal cortex, most commonly due to autoimmune disease (70-90% of cases in developed countries). Other causes include tuberculosis, adrenal hemorrhage, metastatic cancer, HIV, and genetic disorders. Both cortisol and aldosterone deficiency occur, leading to electrolyte abnormalities and characteristic hyperpigmentation from elevated ACTH.
Secondary Adrenal Insufficiency: Pituitary disease causing insufficient ACTH production. Causes include pituitary tumors, surgery, radiation, trauma, or infiltrative diseases. Aldosterone production remains intact (regulated by renin-angiotensin system), so no electrolyte abnormalities or hyperpigmentation occur.
Tertiary Adrenal Insufficiency: Hypothalamic dysfunction with decreased CRH. Most commonly results from chronic exogenous glucocorticoid use suppressing the HPA axis. Recovery can take months to years after stopping steroids.
The gold standard for diagnosing AI. Synthetic ACTH (cosyntropin 250 mcg) is administered IV or IM. Cortisol is measured at baseline, 30 minutes, and 60 minutes. A peak cortisol ≥ 18-20 mcg/dL is considered normal, though some experts use higher cutoffs. This test assesses the adrenal glands' capacity to produce cortisol but cannot distinguish primary from secondary AI without baseline ACTH measurement.
Glucocorticoid replacement is essential for all types of AI. Hydrocortisone 15-25 mg/day in 2-3 divided doses mimics normal diurnal cortisol secretion. Primary AI also requires mineralocorticoid replacement with fludrocortisone 0.05-0.2 mg/day. Patient education on stress dosing is critical - doses must be increased 2-3 times during illness or physiological stress to prevent adrenal crisis.
Chronic symptoms include fatigue (often severe and progressive), weight loss, decreased appetite, muscle weakness, low blood pressure (especially orthostatic), salt craving, nausea, and vomiting. Primary AI causes hyperpigmentation (bronzing of skin, especially in sun-exposed areas, skin creases, and mucous membranes) due to high ACTH levels. Secondary AI doesn't cause hyperpigmentation or electrolyte abnormalities. Symptoms often develop gradually and may be mistaken for other conditions.
Adrenal crisis (acute adrenal insufficiency) is a life-threatening emergency characterized by severe hypotension (shock), confusion, severe weakness, abdominal pain, vomiting, fever, and potentially loss of consciousness. It occurs when someone with AI experiences physiological stress (infection, surgery, trauma) without appropriate stress-dose glucocorticoids. Treatment requires immediate IV hydrocortisone 100 mg, aggressive IV fluids, and ICU care. Mortality can be high if treatment is delayed. This is why all AI patients must carry emergency injection kits.
For minor illness (cold, mild infection): double your usual daily dose for 2-3 days. For moderate illness (fever > 38°C, vomiting, significant infection): triple your dose and contact your doctor. For severe illness or if unable to take oral medications: use emergency IM injection of hydrocortisone 100 mg and go to the ER immediately. For surgery, stress dosing depends on procedure severity - discuss with your surgeon and endocrinologist beforehand. Never skip doses, as your body cannot produce cortisol on its own.
Yes, prolonged exogenous glucocorticoid use (oral, inhaled, topical, or injected) suppresses the HPA axis, causing tertiary AI. The risk increases with higher doses and longer duration. Even inhaled or topical steroids can cause suppression at high doses. After stopping steroids, the HPA axis may take 6-12 months or longer to recover. Patients on steroids for > 3 weeks (or equivalent doses) should not stop abruptly and may need stress dosing during illness. ACTH stimulation testing can assess recovery after steroid discontinuation.
Cortisol follows a circadian rhythm with peak levels around 8 AM and lowest levels at midnight. A morning (8 AM) cortisol is the most sensitive screening test. If morning cortisol is < 3 mcg/dL, AI is very likely. If ≥ 18 mcg/dL, AI is highly unlikely. Values between 3-18 mcg/dL are indeterminate and require ACTH stimulation testing. Random cortisol levels are harder to interpret due to normal variation throughout the day and stress-induced elevation.
It depends on the type of AI. Primary AI (Addison disease) affects the entire adrenal cortex, so both glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) replacement are needed. Secondary and tertiary AI only affect cortisol production - aldosterone production remains intact because it's controlled by the renin-angiotensin system, not ACTH. Therefore, only glucocorticoid replacement is needed for secondary/tertiary AI. Your doctor will determine which medications you need based on your type of AI, electrolytes, and renin/aldosterone levels.
Yes, absolutely. All patients with adrenal insufficiency should wear medical alert identification (bracelet or necklace) at all times. In an emergency, you may be unable to communicate your condition. The medical alert identifies you as having AI and needing stress-dose steroids. It can be lifesaving if you're in an accident, have sudden illness, or lose consciousness. The identification should state "Adrenal Insufficiency - Requires Hydrocortisone" and include emergency contact information.
An emergency injection kit contains hydrocortisone 100 mg for intramuscular injection. Use it if you're unable to take or keep down oral medications (severe vomiting, diarrhea, loss of consciousness, severe illness/injury) or if you have symptoms of adrenal crisis. After administering the injection, call 911 immediately and go to the emergency room. The injection provides temporary cortisol replacement but is not sufficient treatment for adrenal crisis - you need IV hydrocortisone, fluids, and ICU monitoring. Family members should be taught how to give the injection.
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