What is the significance of checking Adrenocorticotropic hormone (ACTH) levels in a patient with central adrenal insufficiency on hydrocortisone (cortisol) replacement therapy?

ACTH Monitoring in Central Adrenal Insufficiency on Hydrocortisone Replacement

Checking ACTH levels in a patient with established central adrenal insufficiency already on hydrocortisone replacement therapy is not clinically useful and should not be routinely performed.

Why ACTH Testing is Not Indicated

Morning cortisol and ACTH measurements in patients actively taking hydrocortisone are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids, with cross-reactivity varying by assay. 1 This creates several critical problems:

• Hydrocortisone must be held for 24 hours before any meaningful cortisol testing can be performed 1
• Laboratory confirmation of adrenal insufficiency should not be attempted in patients given corticosteroids until treatment is ready to be discontinued 2
• If the patient is on established replacement therapy for confirmed adrenal insufficiency, there is usually no reason to check cortisol or ACTH levels—the diagnosis is already made 1

Understanding Central vs. Primary Adrenal Insufficiency

The distinction matters for what you should monitor:

• Central (secondary) adrenal insufficiency is characterized by low ACTH with low cortisol, distinguishing it from primary adrenal insufficiency which presents with high ACTH and low cortisol 1, 3
• In central adrenal insufficiency, ACTH levels will be low or inappropriately normal by definition of the disease 1
• Patients on hydrocortisone for central adrenal insufficiency will have iatrogenic suppression of their already-deficient ACTH production, making the test result meaningless 1

What You Should Monitor Instead

Focus on clinical assessment and practical management rather than biochemical monitoring:

• Assess for signs of under-replacement: lethargy, nausea, poor appetite, weight loss, morning fatigue, orthostatic hypotension 1, 4
• Assess for signs of over-replacement: weight gain, glucose intolerance, hypertension, cushingoid features 1
• Monitor electrolytes periodically to detect hyponatremia which occurs in 90% of adrenal insufficiency cases 1
• Adjust hydrocortisone dosing based on clinical symptoms and timing of symptom occurrence throughout the day 1

Specific Clinical Scenarios Where ACTH Might Be Relevant

There are only two situations where ACTH measurement has clinical utility:

1. Uncertain Diagnosis Requiring Confirmation

• If diagnostic confirmation is still needed and you want to perform testing, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 1
• Paired measurement of early morning (8 AM) serum cortisol and plasma ACTH is the first-line diagnostic test when the diagnosis is uncertain 1

2. Assessing HPA Axis Recovery After Steroid-Induced Suppression

• In patients with isolated central adrenal insufficiency from prior steroid use and no other central hormone deficiencies, the HPA axis should be tested for recovery after 3 months of maintenance therapy with hydrocortisone 2, 1
• Wait until the patient has been weaned off corticosteroids before performing definitive HPA axis testing 1
• In cases of clinical uncertainty with ongoing steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids 1

Common Pitfalls to Avoid

• Do not attempt to use morning cortisol levels to guide hydrocortisone dosing adjustments—the assay cannot distinguish therapeutic from endogenous cortisol 1
• Do not check ACTH levels to assess adequacy of replacement therapy—ACTH will be suppressed by the exogenous hydrocortisone regardless of dose adequacy 1
• Do not delay treatment of suspected adrenal crisis to obtain diagnostic testing—treatment should never be delayed for diagnostic procedures 1

Practical Management Approach

Base hydrocortisone dose adjustments on clinical parameters:

• Standard maintenance dosing is hydrocortisone 15-25 mg daily in divided doses, typically 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM 1
• Educate patients on stress dosing (doubling or tripling doses during illness, surgery, or significant stress) 1, 3
• Ensure patients wear a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by emergency services 1, 3
• Provide emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1