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

Diagnosis and Treatment of Adrenal Insufficiency

Immediate Action for Suspected Adrenal Crisis

If adrenal crisis is suspected clinically, immediately administer hydrocortisone 100 mg IV bolus and rapid isotonic saline infusion (1 L over 1 hour) without waiting for laboratory confirmation, as delayed treatment increases mortality. 1, 2

Emergency Treatment Protocol

• Draw blood for serum cortisol, ACTH, sodium, potassium, creatinine, and glucose before treatment, but never delay therapy for diagnostic procedures 1
• Administer hydrocortisone 100 mg IV bolus immediately, followed by 100-300 mg/day as continuous infusion or divided IV/IM doses every 6 hours 1, 3, 4
• Infuse 0.9% normal saline at 1 L/hour initially, then continue 3-4 L over 24-48 hours with frequent hemodynamic monitoring 1, 3, 4
• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as the patient improves 1, 3
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1

Clinical Presentation of Acute Adrenal Crisis

• Cardinal symptoms: Malaise, fatigue, nausea, vomiting, abdominal pain (sometimes mimicking peritonitis), muscle pain/cramps, and dehydration leading to hypotension and shock 1
• Neurological manifestations: Confusion, impaired cognitive function, loss of consciousness, or coma 1
• Laboratory findings: Hyponatremia (present in 90% of cases), hyperkalemia (50% of cases), elevated creatinine from prerenal failure, hypoglycemia (especially in children), and mild hypercalcemia (10-20% of cases) 1, 2

Diagnostic Approach for Stable Patients

Initial Laboratory Testing

• Obtain early-morning (8 AM) serum cortisol, ACTH, and DHEAS 2, 5
• Primary adrenal insufficiency: Serum cortisol <250 nmol/L (<5 µg/dL) with elevated ACTH confirms diagnosis 2, 5
• Secondary adrenal insufficiency: Low or intermediate cortisol (5-10 µg/dL) with low or inappropriately normal ACTH 2, 5
• Check basic metabolic panel for sodium, potassium, and glucose 1

Confirmatory Testing

• Perform cosyntropin stimulation test if morning cortisol is intermediate (5-10 µg/dL): failure to reach cortisol >550 nmol/L (20 µg/dL) at 30 or 60 minutes confirms adrenal insufficiency 2, 5

Distinguishing Features of Primary vs. Secondary Adrenal Insufficiency

Primary adrenal insufficiency specific findings:

• Hyperpigmentation in sun-exposed areas, skin creases, and mucous membranes due to elevated ACTH 2
• Salt craving due to aldosterone deficiency 2
• Postural hypotension with dizziness or syncope 2
• Hyperkalemia (absent in secondary adrenal insufficiency) 1, 2

Etiologic Workup

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

Maintenance Therapy

Glucocorticoid Replacement

• Hydrocortisone 15-25 mg daily in divided doses (2-3 times daily) is the preferred glucocorticoid 3, 4, 5
• Recommended dosing schedule: 10 mg upon waking, 5 mg at midday, 2.5 mg in early afternoon 3, 4
• Take first dose immediately upon waking; last dose should be at least 6 hours before bedtime to avoid sleep disturbances 3, 4
• Alternative: Cortisone acetate 18.75-31.25 mg daily in divided doses 3
• Alternative: Prednisone 3-5 mg daily 5

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

• Fludrocortisone 50-200 µg once daily is required for all patients with primary adrenal insufficiency 3, 4, 5
• Higher doses (up to 500 µg daily) may be needed in children, younger adults, or during the last trimester of pregnancy 3
• Advise patients to consume salt and salty foods without restriction 3
• Postural hypotension indicates insufficient mineralocorticoid replacement or inadequate salt intake 1

Signs of Inadequate vs. Excessive Replacement

Under-replacement indicators:

• Weight loss, fatigue, postural hypotension, salt craving, persistent hyperpigmentation 3

Over-replacement indicators:

• Weight gain, hypertension, edema 3

Stress Dosing and Illness Management

Minor Illness with Fever

• Double or triple the usual glucocorticoid dose during minor illnesses with fever 3, 4

Major Surgery

• Administer hydrocortisone 100 mg IM before anesthesia, followed by 100 mg IM every 6 hours until able to take oral medications 3, 4

Minor Surgery

• Give hydrocortisone 100 mg IM before anesthesia, then double oral dose for 24 hours 3

Gastrointestinal Illness with Vomiting

• If unable to take oral medications, patients must use emergency injectable hydrocortisone 100 mg IM and seek immediate medical attention 3, 4

Prevention of Adrenal Crisis

Patient Education and Emergency Preparedness

• All patients must wear medical alert identification jewelry 3, 4
• Educate patients to increase steroid doses during intercurrent illnesses, vomiting, injuries, or other stressors 1, 3, 4
• Prescribe emergency injectable hydrocortisone (100 mg IM) and train patients/families on self-administration 5

Common Precipitating Factors

• Gastrointestinal illness with vomiting/diarrhea 1, 3, 4
• Infections (bacterial or viral) 1, 3, 4
• Surgical procedures, injuries, myocardial infarction 1, 3
• Severe allergic reactions 1, 3, 4
• Treatment failures in poorly educated or non-compliant patients 1

Annual Follow-Up and Monitoring

Clinical Assessment

• Evaluate symptoms, weight, blood pressure (including orthostatic measurements) 3, 4
• Assess quality of replacement therapy, self-medication practices during illness, and history of adrenal crises 1

Laboratory Screening

• Serum sodium, potassium, glucose, HbA1c, complete blood count 3, 4
• Thyroid function tests (TSH, free T4, TPO antibodies) annually to screen for autoimmune thyroid disease 1, 3, 4
• Vitamin B12 levels annually to screen for autoimmune gastritis 1, 3
• In women with frequent diarrhea, check tissue transglutaminase antibodies and total IgA for celiac disease 1

Critical Pitfalls and Caveats

Common Management Errors

• Under-replacement with mineralocorticoids is common and predisposes to recurrent adrenal crises 1, 3, 2
• Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies, as this can precipitate adrenal crisis 2
• Essential hypertension in adrenal insufficiency patients should be treated with vasodilators rather than stopping mineralocorticoid replacement 3

Drug Interactions Requiring Dose Adjustments

• Anti-epileptic drugs and barbiturates increase hydrocortisone requirements 3
• Antifungal drugs (especially azoles at high doses) may affect glucocorticoid metabolism 3, 5
• Grapefruit juice and licorice may decrease hydrocortisone requirements 3

Special Populations

• During delivery, administer hydrocortisone 100 mg IV bolus, repeated every 6 hours as necessary 4
• Regular physical activity generally doesn't require dose adjustment, but intense or prolonged exercise may necessitate increased hydrocortisone and salt intake 4