SAT-437 - Secondary Adrenal Insufficiency as an Immune-Related Adverse Event to Pembrolizumab in A Patient with Breast Cancer

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including endocrinopathies such as adrenal insufficiency. Secondary adrenal insufficiency, though less common than primary, may be overlooked, particularly in acutely ill patients with overlapping complications. We present a case of pembrolizumab-induced secondary adrenal insufficiency in a patient with breast cancer.
A female in her 80s with osteoporosis and triple-negative invasive ductal breast carcinoma was receiving neoadjuvant chemotherapy with weekly paclitaxel and pembrolizumab every three weeks. A random cortisol level prior to initiation of immunotherapy was normal at 14.5 µg/dL (reference range 5–23 µg/dL). However, the day before her eighth cycle of pembrolizumab, a morning cortisol level had decreased to 1.5 µg/dL.
Four days later, she was admitted after a fall with increasing fatigue, lightheadedness, and generalized weakness and was found to have a right fibular fracture. During hospitalization, she developed persistent hypotension, metabolic encephalopathy, episodes of hypoglycemia, and worsening hyponatremia, with serum sodium declining from 133 to 126 mmol/L. She was empirically treated with broad-spectrum antibiotics, a broad diagnostic evaluation, including blood cultures, urinalysis, chest radiography, CT of the abdomen and pelvis, and CT and MRI of the brain, was unrevealing. She was concurrently treated with fluconazole for oral candidiasis.
Endocrinology was consulted for evaluation of persistent hypotension and hyponatremia. Repeat morning cortisol levels were low at 1.2 and 0.8 µg/dL, with a suppressed adrenocorticotropic hormone (ACTH) level < 5.0 pg/mL. A cosyntropin stimulation test showed a baseline cortisol of 0.5 µg/dL, with 30-minute cortisol of 2.1 µg/dL and 60-minute cortisol of 2.8 µg/dL. Her TSH was 1.57 μIU/L, and FT4 was 1.1 ng/dL; electrolyte abnormalities included hyponatremia without hyperkalemia or metabolic acidosis.
Based on the clinical presentation, biochemical findings, and temporal association with pembrolizumab therapy, secondary adrenal insufficiency was suspected, with possible contribution from concomitant fluconazole therapy. Treatment with intravenous hydrocortisone 100 mg followed by oral replacement dosing , resulted in rapid clinical improvement and gradual normalization of serum sodium levels.
This case illustrates secondary adrenal insufficiency as a potentially life-threatening irAE of pembrolizumab. A normal baseline cortisol level before immunotherapy supports a treatment-induced etiology. Clinicians should maintain a high index of suspicion for adrenal insufficiency in ICI-treated patients presenting with hypotension, hyponatremia, and nonspecific symptoms, as early corticosteroid replacement is critical to prevent adrenal crisis and improve outcomes.

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