What is the treatment approach for a patient with an Adrenocorticotropic hormone (ACTH) level of 7, indicating potential adrenal insufficiency?

Treatment Approach for ACTH Level of 7

An ACTH level of 7 pg/mL with corresponding low cortisol indicates secondary adrenal insufficiency requiring glucocorticoid replacement therapy with hydrocortisone 15-25 mg daily in divided doses, without the need for mineralocorticoid replacement. 1

Diagnostic Interpretation

• ACTH of 7 pg/mL is inappropriately low or normal in the context of suspected adrenal insufficiency, pointing to secondary (central) adrenal insufficiency rather than primary adrenal disease 1
• Secondary adrenal insufficiency is characterized by low ACTH with low cortisol, distinguishing it from primary adrenal insufficiency which shows high ACTH with low cortisol 1
• You must obtain a paired morning (8 AM) serum cortisol measurement to confirm the diagnosis—if cortisol is <250 nmol/L (<9 μg/dL), this supports adrenal insufficiency 1
• If morning cortisol falls in the indeterminate range (140-400 nmol/L or 5-14 μg/dL), proceed with cosyntropin stimulation test using 250 mcg IV/IM with cortisol measurements at 30 and/or 60 minutes 1

Confirmatory Testing Protocol

• Administer 0.25 mg (250 mcg) cosyntropin intramuscularly or intravenously, preferably in the morning 1
• Measure serum cortisol at baseline and at 30 minutes (and/or 60 minutes) post-administration 1
• A peak cortisol >550 nmol/L (>18-20 μg/dL) is normal, while <500-550 nmol/L is diagnostic of adrenal insufficiency 1
• The high-dose (250 mcg) test is preferred over low-dose (1 mcg) testing due to easier administration, comparable diagnostic accuracy, and FDA approval 1

Treatment Initiation

For mild to moderate symptoms:

• Start hydrocortisone 15-20 mg daily in divided doses (typically 10 mg morning, 5-10 mg afternoon) 1, 2
• Alternative: prednisone 5 mg daily can be used instead of hydrocortisone 1
• Titrate dose based on symptom response, up to maximum of 30 mg hydrocortisone daily 2

For moderate symptoms requiring higher initial dosing:

• Initiate treatment at 2-3 times maintenance dose (30-60 mg hydrocortisone daily) 1, 2
• Taper to maintenance dose over 5-10 days as symptoms improve 2

For severe symptoms or suspected adrenal crisis:

• Immediate IV hydrocortisone 100 mg bolus plus 0.9% saline infusion at 1 L/hour 1
• Do NOT delay treatment for diagnostic testing if the patient is clinically unstable 1

Critical Management Distinctions

• Mineralocorticoid replacement is NOT required in secondary adrenal insufficiency because aldosterone production remains intact (controlled by renin-angiotensin system, not ACTH) 1, 3
• This contrasts with primary adrenal insufficiency, where fludrocortisone 0.1 mg daily is necessary for mineralocorticoid replacement 1, 4
• Hyperkalemia is typically absent in secondary adrenal insufficiency, and hyponatremia—when present—is due to glucocorticoid deficiency affecting free water clearance rather than mineralocorticoid deficiency 1

Workup for Underlying Etiology

• Obtain MRI of the pituitary/hypothalamus to evaluate for structural lesions, masses, or empty sella 1, 5
• Assess other pituitary hormone axes (TSH, LH/FSH, prolactin, IGF-1) as secondary adrenal insufficiency may be part of hypopituitarism 1
• Review medication history for exogenous glucocorticoids (including inhaled steroids like fluticasone) or chronic opioid use, which can suppress the HPA axis 1, 6
• Consider history of traumatic brain injury, pituitary surgery, or radiation therapy 1

Essential Patient Education

• Provide stress-dosing instructions: double or triple maintenance dose during febrile illness, gastroenteritis, or significant physiological stress 1, 7
• Issue medical alert bracelet identifying adrenal insufficiency 1, 7
• Prescribe emergency injectable hydrocortisone (100 mg IM) with training for self/family administration in case of vomiting or inability to take oral medication 7
• Arrange endocrinology consultation prior to any surgical procedures for stress-dose planning 1

Critical Pitfall to Avoid

If the patient has concurrent hypothyroidism requiring thyroid hormone replacement, you MUST start glucocorticoids several days before initiating levothyroxine to prevent precipitating adrenal crisis. 1, 2 Thyroid hormone increases cortisol metabolism and can unmask or worsen adrenal insufficiency if glucocorticoid replacement is not established first.

Follow-Up Monitoring

• Schedule reassessment in 2-4 weeks to evaluate symptom response and adjust dosing 2
• Monitor for signs of over-replacement (weight gain, hypertension, hyperglycemia, insomnia) or under-replacement (persistent fatigue, hypotension, weight loss) 2
• Repeat basic metabolic panel to ensure resolution of hyponatremia if present initially 1
• Long-term monitoring should include annual assessment of other pituitary axes and repeat pituitary imaging if structural lesion was identified 1