From the Guidelines
Central adrenal insufficiency can occur with immunotherapy, particularly with immune checkpoint inhibitors, and requires prompt recognition and treatment to prevent life-threatening adrenal crisis. This condition develops when immunotherapy triggers inflammation in the pituitary gland (hypophysitis), disrupting the production of adrenocorticotropic hormone (ACTH), which normally stimulates cortisol production by the adrenal glands 1. Symptoms of central adrenal insufficiency include fatigue, weakness, dizziness, nausea, low blood pressure, and electrolyte abnormalities.
Diagnosis and Treatment
Diagnosis involves measuring morning cortisol and ACTH levels, with low levels of both suggesting central adrenal insufficiency 1. Treatment typically requires corticosteroid replacement, usually with hydrocortisone (15-20 mg daily in divided doses) or prednisone (5 mg daily), and may also involve fludrocortisone replacement for mineralocorticoid deficiency 1. Patients may need lifelong hormone replacement, though some recover pituitary function after immunotherapy discontinuation.
Management Considerations
It's essential to monitor for this complication during immunotherapy treatment, as early recognition and treatment can prevent potentially life-threatening adrenal crisis 1. Patients with central adrenal insufficiency should be educated on stress dosing, emergency injections, and the use of a medical alert bracelet or necklace 1. Endocrine consultation is recommended for all patients with suspected or confirmed central adrenal insufficiency, and hormone replacement should be initiated promptly to prevent adrenal crisis 1.
Key Points
- Central adrenal insufficiency can occur with immunotherapy, particularly with immune checkpoint inhibitors
- Prompt recognition and treatment are essential to prevent life-threatening adrenal crisis
- Diagnosis involves measuring morning cortisol and ACTH levels
- Treatment typically requires corticosteroid replacement, usually with hydrocortisone or prednisone
- Patients may need lifelong hormone replacement, though some recover pituitary function after immunotherapy discontinuation
- Education on stress dosing, emergency injections, and the use of a medical alert bracelet or necklace is crucial for patients with central adrenal insufficiency 1.
From the Research
Central Adrenal Insufficiency and Immunotherapy
- Central adrenal insufficiency (CAI) is a condition where the production of adrenocorticotropin (ACTH) is impaired, leading to reduced cortisol production 2, 3.
- CAI can be caused by various factors, including pituitary tumors, cranial irradiation, surgery, injury, or infections 2.
- Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has been associated with the development of CAI, specifically isolated ACTH deficiency (IAD) 4.
Prevalence and Clinical Characteristics
- The prevalence of IAD induced by ICI therapy is estimated to be around 0.8% in cancer patients 4.
- The most common symptoms of IAD include fatigue, anorexia, and general malaise 4.
- IAD is often diagnosed at a median time of 7 months after starting immunotherapy, and recovery of the corticotropic axis function is not expected 4.
Diagnosis and Treatment
- Diagnosis of CAI is challenging due to its oligosymptomatic presentation and laboratory investigation pitfalls 3.
- Dynamic tests, such as the Short Synacthen Test (SST), are necessary to confirm or exclude CAI 2.
- Glucocorticoid replacement therapy is required in patients with CAI, and short-acting glucocorticoid drugs, such as hydrocortisone or cortisone acetate, are commonly used 2.
- Provider and patient education are essential in the management of immune checkpoint inhibitor-induced adrenal insufficiency, which may be irreversible and require long-term glucocorticoid and mineralocorticoid replacement 5.