What is the appropriate management for a patient with low morning adrenocorticotropic hormone (ACTH) and borderline low morning cortisol levels?

Management of Low ACTH with Borderline Morning Cortisol (12.4 µg/dL)

This patient has secondary (central) adrenal insufficiency and requires glucocorticoid replacement therapy with hydrocortisone 15-20 mg daily in divided doses (10-15 mg in the morning, 5-10 mg in early afternoon). 1, 2

Diagnostic Interpretation

Your patient's laboratory findings are diagnostic:

• Low ACTH with borderline-low morning cortisol (12.4 µg/dL or ~342 nmol/L) confirms secondary adrenal insufficiency, distinguishing this from primary adrenal insufficiency which would show high ACTH with low cortisol 1, 2
• Morning cortisol between 5-10 µg/dL (140-275 nmol/L) with low or inappropriately normal ACTH is the classic pattern for secondary adrenal insufficiency, though your patient's value at 12.4 µg/dL is borderline 3, 4
• While some sources suggest ACTH stimulation testing for cortisol values in the "gray zone" (5-18 µg/dL), the combination of low ACTH with this borderline cortisol is sufficient for diagnosis in the appropriate clinical context 3, 5

Immediate Management Steps

1. Initiate Glucocorticoid Replacement

• Start hydrocortisone 15-20 mg daily in divided doses: 10-15 mg upon waking and 5-10 mg in early afternoon 1, 2, 4
• This mimics the physiologic diurnal cortisol rhythm 1
• Alternative: Prednisone 3-5 mg daily if adherence to twice-daily dosing is problematic, though hydrocortisone is preferred 1, 4
• No mineralocorticoid (fludrocortisone) is needed since aldosterone production is preserved in secondary adrenal insufficiency 1, 5

2. Evaluate for Additional Pituitary Hormone Deficiencies

• Measure TSH, free T4, LH, FSH, and testosterone (males) or estradiol (premenopausal females) to assess for hypopituitarism 1, 2
• Check basic metabolic panel for hyponatremia (present in 90% of newly diagnosed cases) 3
• If multiple hormone deficiencies are identified, always start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1, 2

3. Determine Underlying Etiology

• Obtain detailed medication history, particularly recent or current glucocorticoid use (including inhaled steroids like fluticasone), which is the most common cause of secondary adrenal insufficiency 3, 6, 4
• Assess for immune checkpoint inhibitor therapy causing hypophysitis 1, 2
• Consider MRI brain with pituitary/sellar cuts if multiple endocrine deficiencies are present, or if patient has new severe headaches or vision changes 1, 2
• Evaluate for opioid use, pituitary tumors, hemorrhage, or infiltrative conditions 4

Critical Patient Education (Non-Negotiable)

Stress Dosing Protocol

• Double or triple the daily hydrocortisone dose during febrile illness, significant infection, or gastrointestinal illness with vomiting/diarrhea 1, 2, 3
• For minor illness: increase to 40-60 mg/day in divided doses 1
• For severe illness, vomiting, or inability to take oral medications: administer hydrocortisone 100 mg intramuscular injection and proceed immediately to emergency department 1, 4

Emergency Preparedness

• Prescribe injectable hydrocortisone 100 mg (Solu-Cortef Act-O-Vial) for home emergency use 4
• Obtain medical alert bracelet or necklace stating "adrenal insufficiency - requires stress-dose corticosteroids" 1, 2
• Provide written instructions on when to self-inject and seek emergency care 1, 2

Surgical/Procedural Planning

• Mandatory endocrinology consultation before any surgery or high-stress procedure for stress-dose planning 1, 2
• Typical perioperative dosing: hydrocortisone 100 mg IV at induction, then 50 mg IV every 6-8 hours, tapering over 2-3 days 1

Monitoring and Follow-Up

• Arrange endocrinology consultation within 2-4 weeks for optimization of therapy and long-term management 1, 2
• Monitor for signs of under-replacement: persistent fatigue, nausea, poor appetite, weight loss, morning symptoms 3
• Monitor for signs of over-replacement: weight gain, hypertension, hyperglycemia, insomnia, mood changes 6
• Follow free T4 (not TSH) if thyroid hormone replacement is also needed, as TSH is unreliable in central hypothyroidism 1

Common Pitfalls to Avoid

• Never delay treatment in symptomatic patients to perform additional testing - if clinical suspicion for adrenal crisis exists (hypotension, altered mental status, severe nausea/vomiting), give hydrocortisone 100 mg IV immediately 1, 3, 7
• Do not start thyroid hormone before corticosteroids in patients with concurrent hypothyroidism - this can precipitate adrenal crisis 1, 2, 8
• Do not rely on absence of hyperkalemia to rule out adrenal insufficiency - hyperkalemia occurs in only ~50% of cases and is more common in primary than secondary adrenal insufficiency 3
• Recognize that patients on chronic glucocorticoids for other conditions will have iatrogenic secondary adrenal insufficiency with low morning cortisol and low ACTH - diagnosis is challenging in this setting 1
• If using dexamethasone 4 mg for emergency treatment when diagnosis is uncertain, ACTH stimulation testing can still be performed afterward (unlike with hydrocortisone) 1, 3