From the Guidelines
Keytruda can cause adrenal insufficiency as a side effect, and patients on this medication should be closely monitored for symptoms of this condition. This occurs because Keytruda is an immune checkpoint inhibitor that works by enhancing the immune system's ability to detect and fight cancer cells, but this enhanced immune response can sometimes attack healthy tissues, including the adrenal glands, as noted in the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update 1. When the immune system attacks the adrenal glands, they may not produce enough cortisol and other essential hormones, resulting in adrenal insufficiency. Symptoms of adrenal insufficiency include fatigue, weakness, dizziness, nausea, vomiting, low blood pressure, and electrolyte abnormalities.
- It is essential to note that the use of corticosteroids for other immune-related adverse events (irAEs) can cause isolated central adrenal insufficiency with a low ACTH, as mentioned in the ASCO guideline update 1.
- The diagnosis of adrenal insufficiency in patients on corticosteroids can be challenging, and laboratory confirmation should not be attempted until treatment is ready to be discontinued, according to the guideline update 1.
- Treatment of adrenal insufficiency typically involves corticosteroid replacement therapy, which may need to be continued long-term, and patients should be educated on stress dosing for sick days, use of emergency steroid injectables, and when to seek medical attention for impending adrenal crisis, as recommended in the guideline update 1.
- Regular monitoring of hormone levels during Keytruda treatment can help detect this condition early, and consulting endocrinology for recovery and weaning protocols using hydrocortisone in patients with symptoms of adrenal insufficiency after weaning off corticosteroids may be necessary, as suggested in the guideline update 1.
From the Research
Adrenal Insufficiency and Keytruda
- Keytruda (pembrolizumab) has been associated with adrenal insufficiency, a rare but potentially life-threatening immune-related adverse event (irAE) 2, 3, 4, 5.
- The incidence of adrenal insufficiency due to pembrolizumab is reported to be between 0.98 and 1.3% 2.
- Adrenal insufficiency can occur during or after treatment with Keytruda, and may be irreversible, requiring long-term glucocorticoid and mineralocorticoid replacement 3, 6.
- Clinical features of adrenal insufficiency include generalized weakness, tachycardia, tachypnea, hypotension, and impaired general health status 2, 4, 5.
- Diagnosis is based on low cortisol levels, measured at any time in case of emergency or else at 8 am, associated with elevated ACTH to rule out pituitary origin 6.
- Treatment with hydrocortisone replacement therapy is essential, and management by an endocrinologist is recommended to adapt hydrocortisone and fludrocortisone replacement therapy 3, 6.
Monitoring and Management
- Provider and patient education are essential in the management of immune checkpoint inhibitor-induced adrenal insufficiency 3.
- Measurements of endocrine function, including cortisol and ACTH levels, should be performed when nonspecific symptoms develop during or after subsequent chemotherapy 4.
- Imaging is recommended to screen for "adrenalitis" or adrenal atrophy and rule out differential diagnosis of adrenal metastasis 6.
- Current data suggest that treatment needs to be life-long, even after termination of immunotherapy 6.