Can cancer or cancer treatment precipitate an adrenal crisis in patients with adrenal insufficiency or those on long-term corticosteroid (cortico-steroid) therapy?

Can Cancer or Cancer Treatment Precipitate Adrenal Crisis?

Yes, cancer and cancer treatment are recognized precipitating factors for adrenal crisis in patients with adrenal insufficiency or those on long-term corticosteroid therapy.

Cancer as a Direct Cause of Adrenal Insufficiency

Secondary adrenal insufficiency can result directly from brain tumors and their treatment, particularly in pediatric populations where pituitary or hypothalamic tumors cause ACTH deficiency 1. In adults, excess mortality in patients with adrenal insufficiency is attributable to malignant diseases, among other causes 1.

• Metastatic disease to the adrenal glands can cause primary adrenal insufficiency and should be evaluated with adrenal CT imaging when autoantibodies are negative 1, 2.
• Brain tumors affecting the hypothalamus or pituitary can cause secondary adrenal insufficiency through ACTH deficiency 1.

Cancer Treatment as a Precipitating Factor

Chemotherapy and Corticosteroid Exposure

Cancer patients receiving chemotherapy that includes corticosteroids are at significant risk for adrenal suppression and subsequent crisis. A landmark study demonstrated that 13 of 14 cancer patients (93%) had suppressed adrenal function for at least 24 hours after short-term high-dose prednisone courses, with five patients remaining suppressed for 7 days or more 3. Critically, four of five patients receiving only 5 days of steroid therapy showed adrenal suppression 3.

• Approximately seven in 1000 people are prescribed long-term oral corticosteroid therapy, creating a population 100 times larger than those with intrinsic adrenal insufficiency and at substantial risk for adrenal crisis 1.
• Glucocorticoid therapy across all routes of administration (oral, inhaled, topical, intranasal, intra-articular) can suppress the hypothalamo-pituitary-adrenal axis 1.

Procedural Stress

Invasive cancer treatments such as transarterial chemoembolization constitute physiological stressors that can trigger adrenal crisis. A fatal case report documented a patient with metastatic sarcoma who died from unrecognized adrenal crisis two days after hepatic artery chemoembolization when stress-dose glucocorticoids were not administered and chronic replacement therapy was accidentally discontinued 4.

• Embolization procedures must be recognized as stressors requiring continuation of chronic corticosteroid replacement and consideration of supplemental stress-dose therapy 4.
• Surgical episodes for cancer treatment are documented precipitating factors for adrenal crisis 1.

Clinical Recognition and Management

High-Risk Scenarios

Any cancer patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise 2.

• Unexplained collapse, hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal crisis 2.
• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases, though hyperkalemia occurs in only ~50% of cases and its absence cannot rule out the diagnosis 2.

Emergency Treatment Protocol

Treatment of suspected acute adrenal insufficiency should NEVER be delayed for diagnostic procedures 1, 2, 5.

• Immediate management: Administer hydrocortisone 100 mg IV bolus immediately without waiting for test results 1, 5.
• Fluid resuscitation: Infuse 0.9% saline at 1 L/hour (at least 2L total) 1, 5.
• Draw blood for cortisol, ACTH, and electrolytes before treatment if possible, but do not delay therapy 1, 5.

Continued Hospital Management

• Continue IV hydrocortisone at 50-100 mg every 6-8 hours for the first 24 hours 5.
• Taper stress-dose corticosteroids over 3-5 days after clinical improvement 5.
• Transition to oral maintenance therapy with hydrocortisone 15-20 mg daily in divided doses 5.

Prevention Strategies

Patient education is critical but current concepts are not sufficiently effective 6.

• Every patient should carry an emergency card and be provided with an emergency kit for parenteral hydrocortisone self-administration 6.
• Patients must wear a medical alert bracelet indicating adrenal insufficiency 1, 5.
• Educate patients to double or triple their dose during illness, fever, or physical stress 7, 5.
• Provide training on emergency injectable hydrocortisone 100 mg IM kit with self-injection instruction 7, 5.

Critical Pitfalls to Avoid

• Never discontinue corticosteroids abruptly in cancer patients, even after short-term therapy, as adrenal suppression can persist for days to weeks 8, 3.
• Do not rely solely on electrolyte abnormalities to make or exclude the diagnosis—some patients have normal electrolytes at presentation 2.
• Mortality from adrenal crisis is high if untreated, with studies suggesting a mortality rate of 0.5/100 patient years 6.
• The symptoms of adrenal crisis are non-specific and can be mistaken for cancer progression or chemotherapy side effects 4.