What are the implications and treatment options for a patient with hypocortisolism and a DHEA (Dehydroepiandrosterone) level of 20?

Adrenal Insufficiency with Severe Cortisol and DHEA Deficiency

This patient has confirmed primary adrenal insufficiency requiring immediate initiation of both glucocorticoid and mineralocorticoid replacement therapy, with consideration for DHEA supplementation after stabilization on primary hormone replacement. 1

Immediate Diagnostic Interpretation

• A cortisol level <1 µg/dL (<27.6 nmol/L) with a DHEA level of 20 µg/dL is diagnostic of severe adrenal insufficiency and requires urgent treatment without delay for additional testing 2, 3
• Measure ACTH immediately to distinguish primary (high ACTH) from secondary (low/normal ACTH) adrenal insufficiency, as this determines whether mineralocorticoid replacement is needed 1, 2
• Check electrolytes urgently: hyponatremia occurs in 90% of cases, but hyperkalemia is only present in ~50% of primary adrenal insufficiency, so normal potassium does not exclude the diagnosis 2
• The extremely low DHEA level (normal range typically 130-980 µg/dL for adults) combined with undetectable cortisol strongly suggests primary adrenal insufficiency with complete loss of adrenal function 3, 4

Immediate Treatment Protocol

For symptomatic patients or those with hypotension/shock:

• Administer hydrocortisone 100 mg IV bolus immediately, do not delay treatment for any diagnostic procedures 1, 2
• Infuse 0.9% normal saline at 1 L/hour (minimum 2L total) 1, 2
• Repeat hydrocortisone 50-100 mg IV every 6-8 hours initially 1
• Taper stress-dose corticosteroids down to oral maintenance doses over 5-7 days 1

For stable outpatients with mild symptoms:

• Start hydrocortisone 15-25 mg daily in divided doses: typically 10 mg at 7 AM, 5 mg at 12 PM, and 2.5-5 mg at 4 PM to mimic physiological cortisol rhythm 1, 2, 3
• Alternative regimens include 15+5 mg, 10+10 mg, or 10+5+5 mg depending on individual response 2
• Prednisone 3-5 mg daily can be substituted if adherence to multiple daily doses is problematic (hydrocortisone 20 mg = prednisone 5 mg) 1, 3

Mineralocorticoid Replacement (Primary AI Only)

If ACTH is elevated confirming primary adrenal insufficiency:

• Start fludrocortisone 0.05-0.1 mg daily as a single morning dose 1, 3
• Adjust based on clinical assessment: salt cravings, orthostatic blood pressure, peripheral edema, serum sodium, and plasma renin activity (target upper half of reference range) 1
• Doses up to 0.2-0.5 mg daily may be needed in younger adults or during pregnancy 1
• Critical pitfall: Under-replacement of mineralocorticoids is common and often compensated by over-replacement of glucocorticoids, predisposing to recurrent adrenal crises 1

DHEA Replacement Considerations

After stabilization on glucocorticoid and mineralocorticoid replacement:

• DHEA replacement is controversial but can be considered, particularly in women with persistent low libido and/or low energy despite optimized primary hormone replacement 1, 5
• Offer a 6-month trial of DHEA 25 mg daily (range 10-50 mg) guided by morning DHEA-sulfate, androstenedione, and testosterone levels maintained in the normal range 1, 5
• Continue only if clinically effective after 6 months, as long-term effects are not fully known 1, 5
• Do not prescribe DHEA to men attempting conception, as it can suppress normal sperm production 5

Etiologic Workup

To determine the underlying cause:

• Measure 21-hydroxylase (anti-adrenal) autoantibodies, as autoimmune adrenalitis accounts for ~85% of primary adrenal insufficiency in Western populations 2
• If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, metastatic disease, tuberculosis, fungal infections, or other structural abnormalities 2
• In males with negative antibodies, assay very long-chain fatty acids (VLCFA) to screen for adrenoleukodystrophy 2

Critical Patient Education and Safety Measures

All patients require immediate education on:

• Stress dosing: Double or triple the usual daily dose during illness, fever, vomiting, diarrhea, or physical stress 2
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training for impending adrenal crisis 2, 3
• Medical alert bracelet or necklace indicating adrenal insufficiency to trigger stress-dose corticosteroids by emergency personnel 1, 2, 3
• Warning signs of adrenal crisis: severe weakness, confusion, abdominal pain, vomiting, hypotension 2

Drug Interactions to Avoid

Medications that increase hydrocortisone requirements:

• Anti-epileptics, antituberculosis drugs, antifungal medications, etomidate, topiramate 2

Medications that interfere with fludrocortisone (avoid or adjust dose):

• Diuretics, acetazolamide, NSAIDs, carbenoxolone, liquorice 1, 2

Substances that potentiate mineralocorticoid effects (avoid):

• Liquorice and grapefruit juice 1, 2

Mandatory Endocrine Consultation

• Arrange urgent endocrinology referral for all newly diagnosed adrenal insufficiency, pre-operative planning, and any patient with recurrent symptoms despite treatment 1, 2
• Endocrine consultation should occur before surgery or high-stress treatments at any time during the patient's care 1

Special Considerations for Concurrent Hypothyroidism

If thyroid hormone replacement is also needed:

• Start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis, as thyroid hormone increases cortisol metabolism 2