What is the diagnosis and treatment for a patient with suspected adrenal insufficiency?

Diagnosis and Treatment of Adrenal Insufficiency

If adrenal crisis is suspected clinically, immediately administer hydrocortisone 100 mg IV bolus and 1 liter of 0.9% saline over one hour without waiting for laboratory confirmation—treatment must never be delayed for diagnostic procedures. 1

Clinical Diagnosis

Acute Presentation (Adrenal Crisis)

The clinical picture includes:

• Cardiovascular collapse: Hypotension, shock, and dehydration 1
• Gastrointestinal symptoms: Nausea, vomiting, abdominal pain (sometimes mimicking an acute abdomen with peritoneal irritation) 1
• Neurological manifestations: Confusion, altered mental status, loss of consciousness, or coma 1
• Laboratory hallmarks: Hyponatremia (present in 90% of cases), hyperkalemia (50% of cases), elevated creatinine from prerenal failure, and occasionally mild hypercalcemia 1, 2

Chronic Presentation

Look for these specific features:

• Primary adrenal insufficiency: Hyperpigmentation in sun-exposed areas, skin creases, and mucous membranes (due to elevated ACTH), salt craving (specific for aldosterone deficiency), postural hypotension with dizziness or syncope 2, 3
• Nonspecific symptoms: Fatigue (50-95% of patients), weight loss (43-73%), anorexia, nausea, and muscle weakness 3, 4

Critical pitfall: Secondary adrenal insufficiency may present with minimal or no symptoms in 5% of cases, and lacks hyperpigmentation and salt craving since ACTH is low 4.

Diagnostic Workup

Initial Laboratory Testing

Draw these tests before initiating treatment (but never delay treatment if crisis is suspected):

• Early morning (8 AM) serum cortisol and ACTH 2, 3
• Serum sodium, potassium, creatinine, glucose 1
• DHEAS (dehydroepiandrosterone sulfate) 3

Interpretation of Results

• Primary adrenal insufficiency: Morning cortisol <250 nmol/L (<5 µg/dL) with elevated ACTH and low DHEAS 2, 3
• Secondary adrenal insufficiency: Low or intermediate cortisol (5-10 µg/dL) with low or inappropriately normal ACTH and low DHEAS 1, 3

Confirmatory Testing

For intermediate cortisol levels (5-10 µg/dL), perform:

• Cosyntropin stimulation test: Administer 250 µg cosyntropin; measure cortisol at baseline, 30, and 60 minutes. Failure to reach >550 nmol/L (>20 µg/dL) confirms adrenal insufficiency 2, 3

Etiologic Workup

Once adrenal insufficiency is confirmed:

• Test for 21-hydroxylase autoantibodies (21OH-Ab): Positive in ~85% of autoimmune Addison's disease cases in Western populations 1, 2
• If 21OH-Ab negative: Obtain adrenal CT scan to evaluate for hemorrhage, metastases, tuberculosis, or infiltrative processes 1, 2

Emergency Treatment of Adrenal Crisis

Immediate Management (Grade 3-4 Severity)

The treatment protocol is non-negotiable and must be initiated immediately: 1

1. Hydrocortisone 100 mg IV bolus given immediately (this saturates 11β-HSD type 2 to provide mineralocorticoid effect) 1
2. Isotonic saline (0.9%) 1 liter over 1 hour, followed by 3-4 liters over 24-48 hours with frequent hemodynamic monitoring 1, 5
3. Continue hydrocortisone 100-300 mg/day as continuous IV infusion or divided IV/IM doses every 6 hours 1, 6
4. Treat precipitating causes: Draw blood cultures and initiate antibiotics if infection suspected 1
5. Consider ICU admission for severe cases with hemodynamic instability 1

Tapering Protocol

• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as clinical condition improves 1, 5
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Maintenance Therapy

Glucocorticoid Replacement

Hydrocortisone is the preferred agent at 15-25 mg daily in divided doses: 6, 5

• Typical regimen: 10 mg upon waking, 5 mg at midday, 2.5 mg in early afternoon 6, 5
• Timing is critical: First dose immediately upon waking; last dose at least 6 hours before bedtime to avoid sleep disturbances 6, 5
• Alternative: Cortisone acetate 18.75-31.25 mg daily in divided doses 6

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

• Fludrocortisone 50-200 µg once daily (higher doses up to 500 µg may be needed in children, young adults, or during third trimester of pregnancy) 6, 5
• Encourage liberal salt intake without restriction 6

Important distinction: Mineralocorticoid replacement is required only for primary adrenal insufficiency, not secondary or glucocorticoid-induced adrenal insufficiency 1, 6.

Stress Dosing Guidelines

Minor Illness with Fever

Double or triple the usual glucocorticoid dose during the illness 6, 5

Major Surgery

• Hydrocortisone 100 mg IM before anesthesia
• Continue 100 mg IM every 6 hours until able to take oral medications 6, 5

Minor Surgery

• Hydrocortisone 100 mg IM before anesthesia
• Double oral dose for 24 hours post-procedure 6

Prevention of Adrenal Crisis

Patient Education (Essential to Reduce Mortality)

All patients must understand: 1, 6, 5

• How to increase steroid doses during intercurrent illness, vomiting, injuries, or stressors
• When to seek immediate medical help before becoming unable to self-care
• Common precipitating factors: Gastrointestinal illness with vomiting/diarrhea, infections, surgical procedures, injuries, severe allergic reactions 6, 5

Emergency Preparedness

• All patients must wear medical alert identification jewelry 6, 5
• Prescribe emergency injectable hydrocortisone 100 mg IM and train patients/families on self-administration 2

Critical pitfall: Under-replacement with mineralocorticoids and low salt intake are common causes of recurrent adrenal crises that are preventable 1, 6.

Annual Follow-Up and Monitoring

Clinical Assessment

• Symptoms, weight, and blood pressure (postural hypotension indicates inadequate mineralocorticoid or salt intake) 1, 6
• Signs of under-replacement: Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation 6
• Signs of over-replacement: Weight gain, hypertension, edema 6

Laboratory Screening

Annual testing should include: 6, 5

• Serum sodium, potassium, glucose, HbA1c, complete blood count
• Thyroid function tests (TSH, free T4, TPO antibodies) to screen for autoimmune thyroid disease
• Vitamin B12 levels to screen for autoimmune gastritis
• Screening for coeliac disease (tissue transglutaminase antibodies and total IgA) if episodic diarrhea present 1

Important consideration: In patients with autoimmune Addison's disease, 58% have associated autoimmune thyroid disorders 4. Never start thyroid hormone replacement before ensuring adequate glucocorticoid replacement, as this can precipitate adrenal crisis 2.

Drug Interactions Requiring Dose Adjustments

Medications affecting glucocorticoid metabolism: 6

• Increase hydrocortisone requirements: Anti-epileptic drugs, barbiturates
• Decrease hydrocortisone requirements: Grapefruit juice, licorice
• May affect metabolism: Antifungal drugs (especially high-dose azoles can cause adrenal insufficiency) 3

Management of hypertension: Treat with vasodilators rather than stopping mineralocorticoid replacement 6.