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Immune-related Adverse Events from Immune Checkpoint Inhibitor Therapy

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32 Treatment Table 4. Endocrine Toxicities G2: Moderate symptoms, able to perform ADL • Consider holding ICPi until patient is stabilized on replacement hormone. • Endocrine consultation. • See in clinic to assess need for hydration, supportive care, and hospitalization. • Initiate outpatient corticosteroid treatment at 2–3 times maintenance (e.g., hydrocortisone 30–50 mg totally dose or prednisone 20 mg daily) to manage acute symptoms. • Initiate fludrocortisone (0.5–0.1 mg/day). • Decrease stress dose corticosteroids down to maintenance doses after 2 days. • Maintenance therapy as in G1. G3–4: Severe symptoms, medically significant or life- threatening consequences, unable to perform ADL • Hold ICPi until patient is stabilized on replacement hormone. • Endocrine consultation. • Inpatient management may be needed to provide: ▶ Normal saline (at least 2L). ▶ IV Stress dose steroids: Hydrocortisone 50–100 mg q6–8h initial dosing. • Taper stress dose corticosteroids down to oral maintenance doses over 5–7 days. • Maintenance therapy as in G1. Additional considerations: • Primary and secondary adrenal insufficiency can be distinguished by the relationship between ACTH and cortisol. If the ACTH is low with low cortisol, then management is as per hypophysitis in section 4.3 for secondary (central) adrenal insufficiency. • Using hydrocortisone allows for re-creation of the diurnal rhythm of cortisol. Typically, 2/3 of the dose is given in the morning and 1/3 in the early afternoon. Long-acting steroids such as prednisone, rather than short-acting hydrocortisone, carries risk of over replacement but can be used in special circumstances, for example, if a patient is not able to adhere to a short-acting steroid regimen. Hydrocortisone 20 mg is equivalent to prednisone 5 mg. • DHEA replacement is controversial but deficiency can be tested and replacement considered in women with low libido and/or energ y who are judged to be otherwise well replaced. • All patients need education on stress dosing for sick days, use of emergency injectables, when to seek medical attention for impending adrenal crisis, and a medical alert bracelet/necklace for adrenal insufficiency to trigger stress dose corticosteroids by emergency medical personnel. Therefore, early endocrinolog y consultation is appropriate. • Endocrine consultation should be part of planning prior to surgery or high-stress treatments such as cytotoxic chemotherapy at any time during a patient's care. (cont'd)

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