What are the next steps for a female patient with a functional neurological disorder and a low serum cortisol level of 3, with the sample collected at 10 am?

Management of Low Serum Cortisol in a Patient with Functional Neurological Disorder

Immediate Next Steps

You must immediately repeat the cortisol measurement with a simultaneous ACTH level to distinguish between primary and secondary adrenal insufficiency, as a single morning cortisol of 3 µg/dL (83 nmol/L) is diagnostic for adrenal insufficiency and requires urgent evaluation. 1, 2

Diagnostic Workup

• Obtain morning (8 AM) cortisol and ACTH simultaneously to determine the etiology: low cortisol with low ACTH indicates secondary (central) adrenal insufficiency, while low cortisol with elevated ACTH indicates primary adrenal insufficiency 3, 1

• Check basic metabolic panel to assess for electrolyte abnormalities (hyponatremia, hyperkalemia) that would suggest primary adrenal insufficiency 2

• Consider ACTH stimulation testing if the diagnosis remains unclear, though with a morning cortisol of 3 µg/dL (83 nmol/L), dynamic testing may not be necessary as this level is diagnostic for adrenal insufficiency 3, 4

• Order pituitary MRI with contrast and sellar cuts if ACTH is low, to evaluate for hypophysitis or other pituitary pathology causing secondary adrenal insufficiency 3, 2

Important Diagnostic Considerations

The morning cortisol of 3 µg/dL is particularly concerning because:

• Research demonstrates that morning cortisol <126.4 nmol/L (~3.6 µg/dL) predicts adrenal insufficiency with 98.7% specificity 4
• A morning cortisol <275 nmol/L (~7.9 µg/dL) identifies subnormal adrenal function with 96.2% sensitivity 5
• Your patient's value falls well below these thresholds, making adrenal insufficiency highly likely 5, 4

Treatment Algorithm Based on Symptom Severity

Grade 1 (Mild Symptoms: fatigue, nausea, poor appetite)

Initiate hydrocortisone 15-20 mg daily in divided doses (typically 10 mg upon awakening, 5 mg in early afternoon) 3, 1, 2

• This mimics the physiological diurnal rhythm with 2/3 of the dose in the morning and 1/3 in the afternoon 3
• Do not use long-acting steroids like prednisone initially as they carry higher risk of over-replacement and don't recreate normal cortisol rhythm 3, 2

Grade 2 (Moderate Symptoms: significant weakness, orthostatic symptoms, able to perform ADLs)

Start hydrocortisone 30-50 mg total daily dose or prednisone 20 mg daily if needed 1, 2

• Consider clinic evaluation for volume repletion if orthostatic symptoms present 3
• Taper to maintenance doses (15-20 mg hydrocortisone) over 5-10 days once stabilized 3

Grade 3-4 (Severe Symptoms: unable to perform ADLs, life-threatening)

Hospitalize immediately for IV hydrocortisone 100 mg bolus, followed by 50-100 mg every 6-8 hours 3, 2

• Administer at least 2 liters normal saline for volume repletion 3
• Taper stress-dose corticosteroids to maintenance over 7-14 days after stabilization 3

Critical Management Principles

If Primary Adrenal Insufficiency (High ACTH)

Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 1, 2

• Higher doses up to 0.2 mg may be needed in younger adults 3
• Advise unrestricted sodium intake and avoid potassium-containing salt substitutes 3

If Secondary Adrenal Insufficiency (Low ACTH)

• No fludrocortisone needed as mineralocorticoid function is preserved 3
• Evaluate other pituitary hormones (TSH, free T4, LH, FSH, estrogen/testosterone) for additional deficiencies 3
• If thyroid replacement is also needed, always start hydrocortisone first and wait at least 1 week before initiating thyroid hormone to prevent precipitating adrenal crisis 3, 1, 2

Essential Patient Education

All patients with confirmed adrenal insufficiency require immediate education on the following life-saving measures:

• Stress dosing: Double or triple hydrocortisone dose during illness, injury, or significant stress 1, 2
• Emergency injectable hydrocortisone with clear instructions for use during vomiting or inability to take oral medications 3, 1
• Medical alert bracelet or necklace identifying adrenal insufficiency to trigger emergency treatment 3, 1, 2
• Signs of adrenal crisis: severe weakness, confusion, abdominal pain, vomiting—seek emergency care immediately 3, 1

Urgent Endocrinology Referral

Refer to endocrinology immediately for:

• Confirmation of diagnosis and etiology 3
• Optimization of replacement therapy 3
• Stress-dose planning before any future procedures or surgeries 3, 6
• Long-term monitoring and management 3

Monitoring for Treatment Adequacy

Signs of Under-Replacement

• Persistent lethargy, nausea, poor appetite, weight loss 3
• Increased skin pigmentation (in primary adrenal insufficiency) 3
• Orthostatic hypotension, salt craving 3

Signs of Over-Replacement

• Weight gain, insomnia, peripheral edema 3
• Bruising, thin skin, hypertension, hyperglycemia 1, 2
• Features of iatrogenic Cushing's syndrome 1, 2

Note: Plasma ACTH and serum cortisol are not useful for monitoring glucocorticoid replacement adequacy—rely on clinical assessment 3

Special Consideration for Functional Neurological Disorder

While the functional neurological disorder may have prompted the initial cortisol testing, the low cortisol finding represents a separate, potentially life-threatening condition that requires immediate treatment regardless of the underlying psychiatric diagnosis. 1, 2 Do not attribute symptoms of adrenal insufficiency (fatigue, weakness, nausea) solely to the functional disorder—these require urgent hormonal replacement.