What is the appropriate management for a patient with elevated inflammation, low cortisol levels, and a DHEA level of 13.7?

Critical Adrenal Insufficiency Requiring Immediate Glucocorticoid and Mineralocorticoid Replacement

This patient has laboratory findings consistent with primary adrenal insufficiency (Addison's disease) and requires immediate initiation of both glucocorticoid and mineralocorticoid replacement therapy without delay for additional testing. 1

Interpretation of Laboratory Findings

The combination of cortisol <1 (severely low), low DHEA of 13.7, and elevated CRP of 21 strongly suggests primary adrenal insufficiency with concurrent inflammation. 1

• Cortisol <1 is critically low - any value <250 nmol/L (<9 μg/dL) with clinical symptoms is diagnostic of adrenal insufficiency and requires immediate treatment 1
• Low DHEA (13.7) confirms adrenal dysfunction - patients with primary adrenal insufficiency are deficient in adrenal androgen secretion including DHEA 2
• Elevated CRP (21) indicates significant inflammation - this inflammatory state increases cortisol requirements and may precipitate adrenal crisis 2

Immediate Management Protocol

Step 1: Assess Clinical Severity

If the patient has ANY of the following, this is an adrenal crisis requiring emergency treatment: 2, 1

• Hypotension (especially orthostatic or requiring vasopressors)
• Nausea, vomiting, or diarrhea
• Abdominal pain
• Confusion or altered mental status
• Unexplained collapse
• Hyponatremia or hyperkalemia

Emergency treatment must NEVER be delayed for diagnostic procedures. 2, 1

Step 2: Initiate Treatment Based on Severity

For Suspected Adrenal Crisis (Severe): 2, 1

• Hydrocortisone 100 mg IV bolus immediately 2, 1
• 0.9% saline infusion at 1 L/hour (minimum 2L total) 2, 1
• Continue hydrocortisone 100 mg IV every 6 hours or 200-300 mg/day as continuous infusion 2
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay treatment 2, 1

For Moderate Symptoms (Stable but Symptomatic): 1

• Start hydrocortisone at 2-3 times maintenance dose (30-50 mg daily in divided doses) 1
• Begin fludrocortisone 0.1 mg daily immediately 2
• Monitor blood pressure, electrolytes, and clinical response 2

For Mild/Stable Outpatient: 1, 3

• Hydrocortisone 15-25 mg daily in divided doses (typical: 10 mg at 7 AM, 5 mg at 12 PM, 2.5-5 mg at 4 PM) 1
• Fludrocortisone 0.05-0.1 mg daily upon awakening 2
• Unrestricted salt intake 1

Step 3: Confirm Diagnosis While Treating

If you need to perform ACTH stimulation testing but must treat immediately: 1

• Use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 1
• However, dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency long-term 1

Standard diagnostic workup (can be done after stabilization): 1

• Morning cortisol and ACTH levels (already have cortisol <1, which is diagnostic) 1
• Measure 21-hydroxylase autoantibodies to identify autoimmune etiology 1
• If autoantibodies negative, obtain adrenal CT imaging 1
• Measure renin and aldosterone levels to confirm mineralocorticoid deficiency 1

Mineralocorticoid Replacement is Essential

Primary adrenal insufficiency requires BOTH glucocorticoid AND mineralocorticoid replacement. 2, 1

• Fludrocortisone 50-200 µg daily (start with 100 µg) 2
• Doses up to 500 µg daily may be needed in younger adults 2
• Monitor by assessing salt cravings, orthostatic blood pressure, and peripheral edema 2
• Under-replacement of mineralocorticoids is common and predisposes to recurrent adrenal crises 2

Avoid these medications that interfere with fludrocortisone: 2

• Diuretics 2
• Acetazolamide 2
• NSAIDs 2
• Liquorice and grapefruit juice 2

DHEA Replacement Consideration

For female patients with persistent low libido or low energy despite optimized glucocorticoid/mineralocorticoid replacement: 2

• Offer a 6-month trial of DHEA 25 mg daily 2
• Monitor morning DHEA-sulfate, androstenedione, and testosterone levels 2
• Continue only if clinically effective 2
• Evidence of benefit is limited, use with caution 2

Critical Patient Education and Safety Measures

All patients with adrenal insufficiency must receive: 1

• Medical alert bracelet or necklace indicating adrenal insufficiency 1
• Injectable hydrocortisone 100 mg IM emergency kit with self-injection training 1
• Instructions to double or triple dose during illness, fever, or physical stress 1
• Education on warning signs of adrenal crisis 1

Stress dosing protocol: 1

• Minor stress: Double usual daily dose for 1-2 days 1
• Moderate stress: Hydrocortisone 50-75 mg daily 1
• Major stress/surgery: Hydrocortisone 100-150 mg daily 1

Common Pitfalls to Avoid

• Never delay treatment for diagnostic testing in suspected adrenal crisis - mortality is high if untreated 2, 1
• Do not rely on electrolyte abnormalities alone - hyperkalemia is present in only ~50% of cases, and 10-20% may have normal electrolytes 1
• Do not stop mineralocorticoid replacement to treat hypertension - add a vasodilator instead, though dose reduction may be considered 2
• Do not use dexamethasone for chronic replacement - it lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 1
• If treating concurrent hypothyroidism, start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 1

Monitoring and Follow-up

• Assess blood pressure (supine and standing), salt cravings, and peripheral edema at each visit 2
• Monitor electrolytes, particularly sodium and potassium 2
• Annual screening for associated autoimmune conditions (thyroid, diabetes, pernicious anemia, celiac disease) 1
• Mandatory endocrine consultation for newly diagnosed patients, pre-operative planning, and recurrent crises 1