Adrenal Dysfunction Management

Diagnostic Approach

The American College of Clinical Oncology recommends AM cortisol as a key diagnostic test for evaluating adrenal function, typically measured between 7:30-8:00 AM when cortisol levels are naturally at their highest 1, 2
Primary and secondary adrenal insufficiency can be distinguished by the relationship between ACTH and cortisol, with low cortisol and high ACTH indicating primary adrenal insufficiency, and low cortisol and low ACTH suggesting secondary adrenal insufficiency 1, 2, 3

For patients with low AM cortisol (adrenal insufficiency), the American College of Clinical Oncology recommends holding immune checkpoint inhibitors until patient is stabilized on replacement hormone, and initiating hormone replacement with hydrocortisone (15-20 mg in divided doses) 1, 3
For patients with high AM cortisol (Cushing syndrome), the National Comprehensive Cancer Network recommends identifying the source through additional testing (24-hour urine cortisol, ACTH levels), and treating based on etiology, such as laparoscopic adrenalectomy for adrenal adenoma, or medical management with adrenostatic agents (ketoconazole 400-1200 mg/day) when surgery is not feasible 4, 5

The American College of Clinical Oncology notes that AM cortisol in patients on corticosteroids is not diagnostic, as therapeutic steroids interfere with cortisol assays, and recommends holding hydrocortisone for 24 hours and other steroids for longer before assessing endogenous function 1, 6
All patients with adrenal insufficiency need education on stress dosing for illness, emergency injectable steroids, and medical alert identification, and should start corticosteroids first when planning hormone replacement therapy for multiple deficiencies to avoid precipitating adrenal crisis 1, 3, 6

Patients with known adrenal insufficiency should not discontinue hydrocortisone for testing without medical supervision due to risk of adrenal crisis 7, 8
For patients undergoing diagnostic evaluation for possible adrenal insufficiency, a standard-dose ACTH stimulation test may be more appropriate than a single cortisol measurement 7, 8

The standard ACTH stimulation test involves administration of 0.25 mg cosyntropin (synthetic ACTH) intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 minutes, with a normal response defined as a cortisol value exceeding 550 nmol/L at either 30 or 60 minutes after ACTH administration 9
If clinical suspicion of impending adrenal crisis exists, treatment with IV hydrocortisone should never be delayed for diagnostic procedures 9

Blood samples for cortisol and ACTH measurement should ideally be secured prior to treatment if possible, but diagnosis can be established later even if treatment has commenced 10