What should be done for a patient with untreated adrenal insufficiency, particularly one who has undergone recent chemotherapy and immunotherapy for cancer?

Immediate Management of Untreated Adrenal Insufficiency in Cancer Patients

This patient requires immediate initiation of hydrocortisone replacement therapy and urgent endocrine consultation, as untreated adrenal insufficiency in the context of recent chemotherapy and immunotherapy is life-threatening and can precipitate adrenal crisis at any moment.

Assess Clinical Severity and Initiate Treatment Immediately

The management approach depends entirely on the patient's current clinical status:

Grade 3-4: Severe Symptoms or Hemodynamic Instability

If the patient has severe weakness, confusion, persistent vomiting, hypotension, or inability to perform activities of daily living:

• Administer IV hydrocortisone 100 mg immediately—do not delay treatment for any diagnostic procedures 1, 2
• Infuse 0.9% saline at 1 L/hour (at least 2L total) for volume resuscitation 1, 2
• Continue hydrocortisone 200 mg/24 hours as continuous infusion or 50-100 mg IV every 6-8 hours 2
• Hold immune checkpoint inhibitor therapy until patient is stabilized on replacement hormones 1
• Obtain urgent endocrine consultation 1
• Taper stress-dose corticosteroids down to maintenance doses over 7-14 days after clinical stabilization 1

Grade 2: Moderate Symptoms, Able to Perform ADL

If the patient has moderate symptoms but remains ambulatory:

• Consider holding immune checkpoint inhibitor until patient is stabilized on replacement hormones 1
• Initiate outpatient treatment at 2-3 times maintenance dosing: hydrocortisone 20-30 mg in the morning and 10-20 mg in the afternoon (or prednisone 20 mg daily) 1
• Obtain endocrine consultation 1
• Taper stress-dose corticosteroids down to maintenance doses over 5-10 days 1

Grade 1: Asymptomatic or Mild Symptoms

If the patient has minimal symptoms:

• Consider holding immune checkpoint inhibitor until patient is stabilized on replacement hormones 1
• Initiate replacement therapy with hydrocortisone 10-20 mg orally every morning, 5-10 mg orally in early afternoon 1
• For primary adrenal insufficiency, add fludrocortisone 0.1 mg/day for mineralocorticoid replacement 1
• Obtain endocrine consultation 1

Distinguish Primary vs. Secondary Adrenal Insufficiency

The distinction is critical because primary adrenal insufficiency requires both glucocorticoid AND mineralocorticoid replacement, while secondary requires only glucocorticoids 1:

• Primary adrenal insufficiency: High ACTH with low cortisol, often with hyponatremia AND hyperkalemia 1, 3
• Secondary adrenal insufficiency: Low ACTH with low cortisol, hyponatremia WITHOUT hyperkalemia 1, 3, 2

Critical Pitfalls to Avoid

Never Delay Treatment for Diagnostic Testing

• Treatment of suspected acute adrenal insufficiency should NEVER be delayed for diagnostic procedures—mortality is high if untreated 1, 3, 2
• If you need to perform ACTH stimulation testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 1

Do Not Rely on Electrolyte Abnormalities Alone

• Hyperkalemia is present in only ~50% of adrenal insufficiency cases, so its absence does NOT rule out the diagnosis 3, 2
• Hyponatremia is present in 90% of cases and can be indistinguishable from SIADH 3, 2

Start Corticosteroids Before Thyroid Hormone

• If the patient has concurrent hypothyroidism (common with hypophysitis from immunotherapy), always start corticosteroids several days before thyroid hormone replacement to prevent precipitating adrenal crisis 1

Mandatory Patient Education and Safety Measures

All patients with adrenal insufficiency require comprehensive education before discharge 1:

• Stress dosing protocols: Double or triple usual dose during illness, fever, or physical stress 1
• Medical alert bracelet: Must wear identification indicating adrenal insufficiency to trigger stress-dose corticosteroids by emergency medical services 1
• Emergency injectable hydrocortisone kit: Prescribe hydrocortisone 100 mg IM with self-injection training 1
• Warning signs of adrenal crisis: Severe weakness, confusion, persistent vomiting, severe abdominal pain, hypotension, inability to take oral medications 4

Coordination with Oncology Team

Notify the oncology team immediately about the adrenal insufficiency diagnosis 4:

• Establish stress-dosing protocols before any cancer treatment procedures 4
• For surgical resection, administer hydrocortisone 100 mg IV at induction of anesthesia, followed by 200 mg/24 hours as continuous infusion or 50-100 mg IV every 6-8 hours 4
• Chemotherapy complications (fever, infection, severe side effects) require stress-dose adjustments 4
• Psychological stress alone (anxiety about cancer diagnosis) does NOT require increased glucocorticoid dosing 4

Long-Term Maintenance Therapy

Once stabilized, transition to maintenance dosing 1, 3:

• Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7:00 AM, 5 mg at 12:00 PM, 2.5-5 mg at 4:00 PM) 3
• Alternative: Prednisone 4-5 mg daily or cortisone acetate 25-37.5 mg daily 1, 3
• For primary adrenal insufficiency: Add fludrocortisone 50-200 µg daily, adjusted based on blood pressure, salt cravings, and plasma renin activity 3
• This is lifelong replacement therapy—never attempt to discontinue in confirmed adrenal insufficiency 3