Is an Adrenocorticotropic hormone (ACTH) level of 10 considered low?

Is an AM ACTH of 10 Considered Low?

An AM ACTH level of 10 pg/mL (approximately 2.2 pmol/L) is definitively low and indicates secondary (central) adrenal insufficiency when accompanied by a low morning cortisol level. 1, 2

Understanding ACTH Interpretation

The interpretation of ACTH depends critically on the corresponding cortisol level, as these must be measured together to distinguish primary from secondary adrenal insufficiency:

Secondary Adrenal Insufficiency Pattern

• Low ACTH with low cortisol is the hallmark of secondary (central) adrenal insufficiency, indicating pituitary or hypothalamic dysfunction 1, 2
• An ACTH of 10 pg/mL falls well below the normal range and suggests inadequate ACTH production from the pituitary 2
• This pattern occurs with pituitary tumors, hypophysitis (including immune checkpoint inhibitor-induced), or iatrogenic suppression from exogenous corticosteroids 1, 3

Primary Adrenal Insufficiency Pattern (For Contrast)

• High ACTH (typically >80 pg/mL or >17.6 pmol/L) with low cortisol indicates primary adrenal insufficiency, where the adrenal glands themselves are failing 2, 4
• The pituitary appropriately increases ACTH production in response to low cortisol feedback 2

Critical Diagnostic Steps

Paired Morning Measurements Are Essential

• Always obtain both morning (8 AM) serum cortisol and plasma ACTH simultaneously 2
• A morning cortisol <250 nmol/L (<9 μg/dL) with low ACTH confirms secondary adrenal insufficiency 2, 4
• A morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH is highly suggestive of secondary adrenal insufficiency 2

Confirmatory Testing

• If morning cortisol is indeterminate (not clearly normal or clearly low), proceed with ACTH stimulation testing using 250 mcg cosyntropin 2
• A peak cortisol <500 nmol/L (<18 μg/dL) at 30 or 60 minutes confirms adrenal insufficiency 1, 2
• The high-dose (250 mcg) test is preferred over low-dose (1 mcg) due to easier administration, FDA approval, and comparable diagnostic accuracy 2

Common Pitfalls to Avoid

Exogenous Steroid Interference

• Patients taking exogenous corticosteroids will have low morning cortisol and low ACTH due to iatrogenic secondary adrenal insufficiency 1, 3
• This includes oral steroids (≥20 mg/day prednisone for ≥3 weeks), inhaled corticosteroids (even at standard doses), and topical/intranasal preparations 2, 3
• Diagnosis of adrenal insufficiency is challenging in these patients—you cannot rely on a simple morning cortisol alone 1
• If you need to treat suspected adrenal crisis but still want diagnostic testing, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone doesn't interfere with cortisol assays 1, 2

Don't Delay Treatment for Testing

• Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures 2, 4
• If the patient is clinically unstable with hypotension, give IV hydrocortisone 100 mg immediately plus 0.9% saline infusion 2
• Draw blood for cortisol and ACTH before treatment if possible, but don't wait for results 2

Electrolytes Are Unreliable

• Unlike primary adrenal insufficiency, secondary adrenal insufficiency typically does not cause hyperkalemia because aldosterone production (controlled by the renin-angiotensin system) remains intact 1, 3
• Hyponatremia may still occur in 90% of cases, but normal electrolytes cannot rule out the diagnosis 2

Clinical Context Matters

High-Risk Scenarios for Secondary Adrenal Insufficiency

• Any patient on ≥20 mg/day prednisone or equivalent for ≥3 weeks who develops unexplained hypotension 2
• Patients with pituitary tumors or history of pituitary surgery/radiation 3
• Patients on immune checkpoint inhibitors who develop hypophysitis 1
• Asthmatic patients on chronic inhaled steroids (35% may have subclinical adrenal suppression) 5

Additional Pituitary Hormone Deficiencies

• When ACTH is low, evaluate for other pituitary hormone deficiencies: TSH, LH, FSH, and consider MRI of the pituitary 1
• Always start corticosteroids several days before thyroid hormone replacement to prevent precipitating adrenal crisis 1, 2

Management Implications

If secondary adrenal insufficiency is confirmed with low ACTH and low cortisol:

• Lifelong glucocorticoid replacement therapy is required: hydrocortisone 15-25 mg daily (divided doses) or prednisone 4-5 mg daily 2
• No mineralocorticoid replacement (fludrocortisone) is needed, unlike primary adrenal insufficiency 2
• Mandatory patient education on stress dosing (doubling doses during illness) 1, 2
• Medical alert bracelet for adrenal insufficiency 1, 2
• Endocrine consultation for ongoing management and pre-operative stress-dose planning 1, 2