Assessment and Investigations:

• Adrenalitis Unlikely
  • 8 am or random cortisol >160 µg/L
• Possible
  • 8 am cortisol 70-160 µg/L
  • Or random cortisol 30-160 µg/L
• Likely
  • 8 am cortisol <70 µg/L
  • Or random cortisol <30 µg/L

Management

1. Await hormonal assessment (<24h)
2. Start physiological substitution with hydrocortisone 10-5-5mg if adrenalitis possible or likely
3. Continue ICPI once adequately substituted

Assessment and Investigations

1. Adrenal crisis, rule out sepsis

• Adrenalitis Unlikely: Random cortisol >160 µg/L
• Likely: Random cortisol <160 µg/L

Management

1. Urgent hydrocortisone stress dose of hydrocortisone 100mg IV (or IM)
2. Intravenous hydration
3. Hold ICPI
4. Taper to physiological substitution in consultation with Endocrinology
5. Measure renin-aldosterone and start fludrocortisone in consultation with Endocrinology
6. Restart ICPI once adequately substituted

Purple: general categories or stratification; turquoise: combination of treatments or other systemic treatments; white: other aspectsof management. ACTH, adrenocorticotrophic hormone; HRT, hormone replacement therapy; ICI, immune checkpoint inhibitor; i.v. intravenous; K,potassium; LLN, lower limit of normal; MRI, magnetic resonance imaging; Na, sodium; q.d.s., four times a day.

a  Maintenance HRT in divided doses: 15-20 mg hydrocortisone; if intercurrent illness, higher doses will be required; if symptomatic,initiation at double the standard dose may be required, with a plan to wean down over 7 days, if a patient is not able to adhere to a short-acting steroid regimen. Hydrocortisone 20 mg is equivalent to prednisone 5 mg. Diagnostic measures should never delay the initiation of steroid replacement therapy in suspected adrenal insufficiency. In primary adrenal insufficiency, mineralocorticoid replacement is also indicated (0.1 mg per day of fludrocortisone) — seek endocrinologist advice.

b Differential diagnoses of low cortisol, i.e. with high ACTH: adrenalitis; with low ACTH: hypophysitis, pituitary tumour or exogenousadrenal suppression, e.g. from concurrent steroid use (e.g. dexamethasone >0.75 mg, prednisolone >3 mg; also consider steroidinhalers).

c Dexamethasone emergency replacement may be useful in cases where the diagnosis of primary adrenal insufficiency issuspected as it will interfere less with assessment of an ACTH stimulation test.