What is the next step in managing a patient with hypocortisolism (low morning plasma cortisol level) and normal aldosterone level?

Next Step: Perform ACTH Stimulation Test

The next step is to perform an ACTH stimulation test to confirm adrenal insufficiency and assess adrenal reserve, while simultaneously measuring ACTH levels to differentiate between primary and secondary adrenal insufficiency. 1, 2

Interpretation of Current Laboratory Values

• A morning cortisol of 8 μg/dL is borderline low and concerning for adrenal insufficiency, as levels >14 μg/dL effectively rule out this diagnosis 3
• The aldosterone level of 7 ng/dL is within normal range, suggesting preserved mineralocorticoid function and pointing away from primary adrenal insufficiency (Addison's disease) 1, 4
• Undetectable plasma norepinephrine is unusual but does not directly inform the cortisol axis evaluation 5

Diagnostic Workup Priority

Immediate testing should include:

• ACTH stimulation test (cosyntropin 250 mcg IV/IM with cortisol measurements at 0,30, and 60 minutes) to assess adrenal reserve—a peak cortisol <18-20 μg/dL confirms adrenal insufficiency 1, 5
• Simultaneous plasma ACTH measurement before stimulation to differentiate primary (elevated ACTH) from secondary (low/normal ACTH) adrenal insufficiency 5
• Basic metabolic panel to evaluate for electrolyte abnormalities, particularly hyponatremia which can occur in adrenal insufficiency 2

Important Caveat About ACTH Stimulation Testing

• ACTH stimulation can give false-negative results early in secondary adrenal insufficiency (such as hypophysitis) because adrenal reserve declines slowly after loss of pituitary stimulation 1
• In the presence of clinical uncertainty with borderline cortisol values and symptoms, opt for initiating replacement therapy and retest for ongoing need at 3 months 1

Clinical Assessment While Awaiting Results

Evaluate symptom severity to guide urgency:

• Mild symptoms (fatigue, nausea, poor appetite): Outpatient workup is appropriate with close follow-up 1, 2
• Moderate symptoms (significant weakness, orthostatic symptoms, weight loss): Consider same-day endocrine consultation and possible empiric treatment 1, 2
• Severe symptoms (hypotension, altered mental status, severe weakness): Immediate hospitalization with IV stress-dose steroids (hydrocortisone 50-100 mg IV Q6-8 hours) and IV normal saline (at least 2L) before confirmatory testing 1, 2

If Adrenal Insufficiency is Confirmed

Initiate glucocorticoid replacement based on severity:

• For confirmed diagnosis with mild-moderate symptoms: Start hydrocortisone 15-20 mg daily in divided doses (typically 10 mg upon awakening, 5 mg at noon, and 2.5-5 mg in mid-afternoon) 1, 2
• The total daily dose range is 15-25 mg hydrocortisone, individualized by weight and clinical response 1, 6
• Critical safety principle: Always start corticosteroids first before initiating any other hormone replacement (such as thyroid hormone) to prevent precipitating adrenal crisis 1, 2

Patient Education Requirements

• All patients with confirmed adrenal insufficiency need education on stress dosing for sick days (double or triple the usual dose during illness) 1, 2
• Provide instruction on use of emergency injectable hydrocortisone and when to seek immediate medical attention 1
• Recommend obtaining a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by emergency medical services 1, 2

Follow-up Monitoring

• Schedule endocrinology consultation for all patients with confirmed adrenal insufficiency 1, 2
• Clinical assessment is the primary monitoring tool—symptoms of over-replacement include weight gain, insomnia, and peripheral edema; under-replacement presents as lethargy, nausea, poor appetite, and weight loss 1
• Plasma ACTH and serum cortisol are not useful for dose adjustment once on replacement therapy 1