In a 22‑year‑old patient who presented with an acute hypoglycemic episode, was stabilized with glucose, and had a random cortisol of 8 µg/dL during the event (inappropriately low for stress), should empiric glucocorticoids be started from an oncology standpoint?

Should Empiric Steroids Be Started From an Oncology Standpoint?

No, empiric glucocorticoids should NOT be started from an oncology standpoint in this 22-year-old patient with a single hypoglycemic episode and a random cortisol of 8 µg/dL, because this cortisol level does not meet diagnostic criteria for adrenal insufficiency, the patient is not on immune checkpoint inhibitor therapy, and starting steroids without confirmed adrenal insufficiency can cause significant harm including steroid-induced hyperglycemia and suppression of the hypothalamic-pituitary-adrenal axis. 1

Diagnostic Threshold Not Met

• A random cortisol of 8 µg/dL during acute hypoglycemia is inappropriately low but not diagnostic of adrenal insufficiency, as the diagnostic threshold requires a morning cortisol <3 µg/dL to confirm primary adrenal insufficiency. 1
• For definitive diagnosis, an AM cortisol with concurrent ACTH level is required, along with consideration of a standard-dose ACTH stimulation test for indeterminate results (AM cortisol >3 µg/dL and <15 µg/dL). 1
• The cortisol response to hypoglycemia can be blunted or inappropriately low in various conditions including hyperinsulinemic states, without indicating true adrenal insufficiency. 2

No Oncologic Indication for Empiric Steroids

• From an oncology standpoint, empiric glucocorticoids are indicated specifically for immune checkpoint inhibitor (ICI)-related endocrinopathies, particularly hypophysitis with central adrenal insufficiency or severe immune-related adverse events. 1
• There is no mention of ICI therapy in this patient, which is the primary oncologic context where empiric steroids would be considered. 1
• For ICI-related hypophysitis with Grade 1 symptoms (asymptomatic or mild), the recommendation is to hold ICI and start replacement hormones (hydrocortisone 10-20 mg in morning, 5-10 mg in early afternoon), not high-dose empiric steroids. 1
• High-dose empiric steroids (prednisone 1-2 mg/kg daily) are reserved for Grade 3-4 symptoms (severe, life-threatening, unable to perform activities of daily living) in the ICI context. 1

Risks of Empiric Steroid Therapy

• Steroid-induced hyperglycemia occurs in 35-39.5% of patients on glucocorticoids, with the degree of hyperglycemia correlating with steroid dose. 1
• Glucocorticoid use can cause isolated central adrenal insufficiency, making subsequent diagnostic workup impossible until steroids are discontinued. 1
• Laboratory confirmation of adrenal insufficiency cannot be performed in a patient already on corticosteroids for other conditions. 1
• Starting steroids empirically may mask the underlying diagnosis and create iatrogenic complications. 3

Appropriate Next Steps Instead

• Complete the diagnostic workup first: Obtain AM cortisol and ACTH levels, basic metabolic panel (sodium, potassium, CO₂, glucose), and consider ACTH stimulation test. 1
• Investigate the cause of hypoglycemia: This young patient's hypoglycemia requires evaluation for other etiologies including insulinoma, insulin autoimmune syndrome, medication effects, or reactive hypoglycemia. 4, 5
• Verify glucose readings with laboratory venous samples, as capillary readings can be inaccurate. 4
• Immediate hypoglycemia management: Administer 15-20 grams of oral glucose if symptomatic and conscious, recheck in 15 minutes, and provide education on carrying fast-acting glucose sources. 6, 7

When Steroids Would Be Indicated

• If confirmed primary adrenal insufficiency (AM cortisol <3 µg/dL with elevated ACTH >2-3× ULN), start hydrocortisone 15-20 mg daily in divided doses (two-thirds in morning, one-third in early afternoon). 1
• If Grade 2-3 adrenal crisis develops (moderate to severe symptoms, unable to perform ADL), initiate stress-dose corticosteroids: hydrocortisone 50-100 mg IV every 6-8 hours initially, then taper to maintenance over 5-7 days. 1
• If on ICI therapy with confirmed hypophysitis, start replacement therapy and consider pulse-dose prednisone only for Grade 3-4 symptoms. 1

Critical Pitfall to Avoid

• Do not start empiric steroids based solely on a single inappropriately low cortisol during hypoglycemia in a patient without confirmed adrenal insufficiency or ICI therapy, as this creates diagnostic confusion, potential harm from steroid side effects, and delays identification of the true underlying cause. 1, 3