How should a patient with an ACTH stim test showing cortisol levels of 1.8, 5.3, and 7.8 mcg/dL at baseline, 30 minutes, and 60 minutes after cosyntropin administration be managed?

ACTH Stimulation Test Results Interpretation

Test Results Indicate Adrenal Insufficiency

Your patient has adrenal insufficiency based on a peak cortisol of 7.8 mcg/dL (215 nmol/L) at 60 minutes, which is well below the diagnostic threshold of 18 mcg/dL (500 nmol/L). 1

Diagnostic Interpretation

• The baseline cortisol of 1.8 mcg/dL is severely low, strongly suggesting adrenal insufficiency even before stimulation testing 1
• The 60-minute peak of 7.8 mcg/dL is diagnostic of adrenal insufficiency, as values <18 mcg/dL (500 nmol/L) confirm the diagnosis 1, 2
• The delta cortisol (change from baseline) is only 6.0 mcg/dL, which is also below the threshold of 9 mcg/dL used in some contexts for critical illness-related corticosteroid insufficiency 3
• Both the 30-minute (5.3 mcg/dL) and 60-minute (7.8 mcg/dL) values are inadequate, with 54% of patients reaching peak cortisol at 60 minutes rather than 30 minutes 4

Determine Primary vs. Secondary Adrenal Insufficiency

Immediately measure baseline ACTH and electrolytes to differentiate the etiology:

• If ACTH is elevated with low cortisol: Primary adrenal insufficiency (Addison's disease) 1, 2

  • Check for hyperkalemia and hyponatremia (though hyperkalemia occurs in only ~50% of cases) 2
  • Measure 21-hydroxylase autoantibodies (positive in ~85% of Western cases) 2
  • If autoantibodies negative, obtain adrenal CT imaging to evaluate for hemorrhage, tumor, or infiltrative disease 2

• If ACTH is low or inappropriately normal with low cortisol: Secondary adrenal insufficiency 1, 2

  • Obtain pituitary MRI to evaluate for pituitary or hypothalamic pathology 5
  • Assess other pituitary hormone axes (TSH, LH/FSH, prolactin, IGF-1) 2

Immediate Management

Start glucocorticoid replacement therapy immediately—do not delay treatment for additional diagnostic workup if the patient is symptomatic:

For Stable Outpatients:

• Hydrocortisone 15-25 mg daily in divided doses (typical: 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 2
• Alternative: Prednisone 4-5 mg daily in the morning 2

For Primary Adrenal Insufficiency (once confirmed):

• Add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 1, 2
• Titrate based on blood pressure, salt cravings, orthostatic symptoms, and plasma renin activity 2
• Encourage unrestricted salt intake 2

For Moderately Symptomatic Patients:

• Start at 2-3 times maintenance dosing (hydrocortisone 30-50 mg daily or prednisone 20 mg daily) 2
• Taper to maintenance over several days as symptoms improve 2

For Critically Ill or Suspected Adrenal Crisis:

• Hydrocortisone 100 mg IV bolus immediately 1, 2
• 0.9% saline infusion at 1 L/hour (at least 2L total) 2
• Continue hydrocortisone 50 mg IV every 6 hours or 200 mg/24-hour continuous infusion 2
• Never delay treatment for diagnostic procedures in suspected adrenal crisis 3, 1, 2

Critical Patient Education and Safety Measures

All patients with confirmed adrenal insufficiency require:

• Medical alert bracelet or necklace indicating adrenal insufficiency 2
• Stress-dose education: Double or triple dose during illness, fever, or physical stress 2
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training 2
• Written sick-day management plan with specific instructions on when to increase doses 2

Important Pitfalls to Avoid

• Do not rely on electrolyte abnormalities alone—hyperkalemia is present in only ~50% of primary adrenal insufficiency cases, and secondary adrenal insufficiency typically has normal potassium 2
• Do not use dexamethasone for chronic replacement therapy—it lacks mineralocorticoid activity and cannot replicate physiologic cortisol rhythm 2
• If treating concurrent hypothyroidism, start corticosteroids several days before thyroid hormone replacement to prevent precipitating adrenal crisis 2
• Avoid testing for adrenal function while patient is on exogenous steroids—this will yield false results showing expected HPA suppression 2
• Check for drug interactions: Anti-epileptics, rifampin, and antifungals increase hydrocortisone requirements; grapefruit juice and licorice decrease requirements 2

Follow-Up and Monitoring

• Endocrinology consultation is mandatory for newly diagnosed adrenal insufficiency, pre-operative planning, and stress-dose protocols 2
• Annual screening for associated autoimmune conditions: thyroid function, diabetes, vitamin B12 deficiency, celiac disease 2
• Reassess adequacy of replacement based on symptom control, blood pressure (supine and standing), weight, and energy levels 2
• For primary adrenal insufficiency: Monitor plasma renin activity to guide fludrocortisone dosing 2