Abstract Background Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are associated with immune-related adverse events (irAEs), including life-threatening endocrinopathies. Adrenal insufficiency and thyroiditis are rare complications that may mimic sepsis, leading to diagnostic delay and inappropriate management in critically ill patients. Recognition and treatment in the intensive care unit (ICU) are essential to prevent mortality. Case Presentation A 78-year-old man with recurrent non-small cell lung cancer receiving pembrolizumab presented with progressive weakness, confusion, and hypotension (blood pressure 92/54 mmHg). Laboratory studies revealed hyponatremia (130 mmol/L), hypoglycemia (65 mg/dL), and mild transaminitis. Despite aggressive fluid resuscitation and broad-spectrum antibiotics for presumed sepsis, hypotension persisted, necessitating initiation of norepinephrine for circulatory support. Supplemental oxygen via nasal cannula was also required. Endocrine evaluation demonstrated a random cortisol of 3 µg/dL, adrenocorticotropic hormone (ACTH) 5 pg/mL, low aldosterone, and suppressed thyroid-stimulating hormone (TSH) (0.063 µIU/mL) with elevated free thyroxine (T4) (1.8 ng/dL), findings consistent with secondary adrenal insufficiency and destructive thyroiditis. Initiation of stress-dose hydrocortisone (100 mg IV every eight hours) led to rapid hemodynamic stabilization and improvement in mental status. The patient was transitioned to physiologic steroid replacement and discharged to a skilled nursing facility with outpatient endocrinology follow-up. Discussion ICIs enhance cytotoxic T-cell activation by blocking inhibitory immune pathways but can also provoke autoimmune injury to endocrine organs. The pituitary and thyroid glands are most frequently affected, resulting in hypophysitis, thyroiditis, and secondary adrenal insufficiency. These irAEs may arise weeks to months after therapy initiation and often present with nonspecific symptoms such as fatigue, hypotension, or electrolyte abnormalities. In this case, pembrolizumab-induced hypophysitis caused secondary adrenal insufficiency, manifesting as refractory hypotension initially misattributed to septic shock. Rapid improvement following corticosteroid therapy underscores the importance of early recognition and intervention. Because endocrine irAEs can closely resemble sepsis, clinicians should maintain a high index of suspicion in ICI-treated patients presenting with unexplained shock, hyponatremia, or altered mental status. Prompt administration of empiric stress-dose corticosteroids and close collaboration among critical care, oncology, and endocrinology teams are essential to optimize outcomes and guide decisions regarding continuation of immunotherapy. Conclusions In critically ill patients receiving ICIs, unexplained hypotension, hyponatremia, or confusion should raise suspicion for adrenal insufficiency and thyroid dysfunction. Early evaluation and empiric corticosteroid therapy are lifesaving measures that prevent misclassification of endocrine irAEs as septic shock. This abstract is funded by: None
Formanek et al. (Fri,) studied this question.