Should Adrenocorticotropic Hormone (ACTH) levels be monitored in patients with adrenal insufficiency?

ACTH Monitoring in Adrenal Insufficiency

ACTH should be measured at initial diagnosis to distinguish primary from secondary adrenal insufficiency, but routine ACTH monitoring during ongoing treatment is not recommended for most patients—instead, focus on clinical assessment and electrolyte monitoring.

Initial Diagnostic Role of ACTH

ACTH measurement is essential at diagnosis to differentiate the type of adrenal insufficiency:

• Morning serum cortisol and plasma ACTH measurements together distinguish primary from secondary adrenal insufficiency and establish baseline values 1
• Primary adrenal insufficiency shows high ACTH with low cortisol, while secondary adrenal insufficiency demonstrates low ACTH with low cortisol 2, 3
• A basal cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 2
• This distinction is clinically critical because primary adrenal insufficiency requires both glucocorticoid and mineralocorticoid replacement, whereas secondary adrenal insufficiency typically requires only glucocorticoid replacement 2

ACTH Monitoring During Treatment

Routine ACTH monitoring during established treatment has limited clinical utility:

• Research shows large inter-individual variations in ACTH levels (ranging from 2-2,249 ng/L) even on standardized replacement therapy, indicating varying individual sensitivity to cortisol 4
• ACTH levels correlate negatively with plasma cortisol at specific time points, but this relationship is highly variable between patients 4
• The primary value of ACTH monitoring appears to be in dose titration for individual patients with primary adrenal insufficiency, where persistently elevated ACTH may suggest under-replacement 4

Recommended Ongoing Monitoring Strategy

For patients on established replacement therapy, focus on these parameters instead:

• Serum electrolytes (sodium, potassium) should be monitored regularly to assess mineralocorticoid replacement adequacy in primary adrenal insufficiency and detect over-replacement 1
• Morning cortisol levels can be measured periodically to assess if replacement dosing is appropriate, though interpretation is complex in patients on exogenous steroids 1
• Clinical assessment remains paramount—monitor for signs of under-replacement (fatigue, hypotension, weight loss) or over-replacement (weight gain, hypertension, hyperglycemia) 2, 3

Important Caveats

Key pitfalls to avoid:

• Laboratory confirmation should not be attempted in patients on high-dose corticosteroids for other conditions until treatment is ready to be discontinued, as results will be uninterpretable 1
• Exogenous steroid use (prednisolone, dexamethasone, inhaled fluticasone) can affect test results 2
• Never delay treatment of suspected acute adrenal crisis to obtain diagnostic tests, as adrenal crisis is life-threatening and requires immediate IV hydrocortisone and fluid resuscitation 1, 3

Special Situations Requiring ACTH Assessment

Consider ACTH measurement in these clinical scenarios:

• When symptoms suggest inadequate replacement despite seemingly appropriate dosing—ACTH can help identify under-replacement in primary adrenal insufficiency 4
• When transitioning from secondary to possible primary adrenal insufficiency (e.g., progressive pituitary disease affecting the adrenal glands directly) 2
• Before surgery or procedures requiring stress-dose planning, ensure endocrine consultation for adequate cortisol coverage verification 1