Why should adrenocorticotropic hormone (ACTH) levels be measured every few months in a patient with adrenal insufficiency?

ACTH Monitoring in Adrenal Insufficiency

ACTH levels are generally NOT checked every few months in patients with established adrenal insufficiency on stable replacement therapy—this is a common misconception. The diagnosis is already confirmed, and routine ACTH monitoring does not guide treatment adjustments or improve outcomes 1.

Why ACTH Monitoring Is Not Routinely Recommended

The consensus guidelines explicitly state that serum and urine cortisol measurements are "usually impossible to interpret" in patients on replacement therapy, and the same principle applies to ACTH levels 1. Here's why:

• In primary adrenal insufficiency, ACTH will remain persistently elevated regardless of adequate replacement therapy because the adrenal glands cannot respond—checking it repeatedly provides no actionable information 1
• In secondary adrenal insufficiency, ACTH will remain suppressed due to the underlying pituitary/hypothalamic dysfunction—again, serial measurements don't change management 2
• Morning cortisol measurements in patients actively taking corticosteroids are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids, with cross-reactivity varying by assay 3

What Should Actually Be Monitored

Annual follow-up should focus on clinical assessment and screening for complications, not ACTH levels 1:

Clinical Parameters (Every Visit)

• Blood pressure assessment (supine and standing) to evaluate mineralocorticoid adequacy—postural hypotension reflects insufficient fludrocortisone or low salt intake 1
• Weight stability—weight loss suggests under-replacement, glucocorticoid excess from other causes, or new autoimmune disease 1
• Symptom assessment including energy levels, appetite, salt cravings, and signs of over- or under-replacement 1

Laboratory Monitoring (Annual)

• Serum sodium and potassium to assess mineralocorticoid replacement adequacy 1
• Thyroid function (TSH, FT4, TPO-Ab) every 12 months—hypothyroidism develops frequently in autoimmune adrenal insufficiency 1
• Plasma glucose and HbA1c to screen for diabetes mellitus 1
• Complete blood count and vitamin B12 levels to screen for pernicious anemia 1
• Tissue transglutaminase antibodies and total IgA in patients with frequent diarrhea to screen for celiac disease 1

Specialized Testing (When Indicated)

• Plasma renin activity (PRA) can be valuable in patients with features of mineralocorticoid deficiency to guide fludrocortisone dosing 1
• Morning cortisol day curve (before and 2,4, and 6 hours after morning dose) only when suspecting under-replacement or rapid cortisol clearance—not routinely 1
• Bone mineral density every 3-5 years to monitor for glucocorticoid-related complications 1

When ACTH Measurement IS Useful

ACTH measurement has diagnostic value in specific scenarios, but not for routine monitoring 3:

• Initial diagnosis: Distinguishing primary (high ACTH, low cortisol) from secondary (low ACTH, low cortisol) adrenal insufficiency 3
• Acute presentation: Basal cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1, 3
• Pre-treatment evaluation: Securing ACTH and cortisol levels before initiating emergency treatment in suspected adrenal crisis 1

Common Pitfalls to Avoid

• Don't order serial ACTH levels in patients with confirmed adrenal insufficiency on stable replacement—it provides no clinical benefit and wastes resources 1, 3
• Don't attempt to use cortisol or ACTH levels to "dose-adjust" replacement therapy—clinical assessment (symptoms, blood pressure, electrolytes) is far more reliable 1
• Don't check morning cortisol in patients actively taking hydrocortisone or prednisone—the assay cannot distinguish endogenous from exogenous steroid 3
• Never delay treatment of suspected adrenal crisis to obtain ACTH levels—treat immediately and draw labs beforehand if possible 1, 3

Focus annual monitoring on screening for associated autoimmune conditions (especially hypothyroidism), assessing replacement adequacy through clinical parameters and electrolytes, and reinforcing patient education on stress dosing and emergency management 1, 3.