Case Presentation: A 69yo man was seen in preop clinic before cystoprostatectomy for a very large bladder tumor that had excellent radiographic response to pembrolizumab. His recent history was notable for an episode of witnessed syncope 5 weeks prior attributed to dehydration in the setting of baseline, long-standing intermittent episodes of SVT. Outpatient ECHO and nuclear medicine stress tests were normal. At his dedicated preop clinic visit, he reports no interval recurrent syncope but confirmed ongoing generalized weakness and fatigue. He had no dyspnea, chest pain, or sensations of palpitations or tachyarrhythmias. Initial vitals were normal including blood pressure and heart rate. In preop clinic, he had a witnessed syncopal episode with BP 81/54 and dropping further to 66/42 despite starting IV fluids in clinic and elevating his legs. HR remained 60bpm. He was transferred to the ED. Because of his immunotherapy, concern for pembrolizumab-induced adrenal insufficiency was signed out to the ED team by the physician in preop clinic. A random midday cortisol level was low at 0.7. ACTH stimulation test showed cortisol undetectable, 2.1, and 3.6 at zero, 30, and 60 minutes respectively, confirming the diagnosis of adrenal insufficiency. He was diagnosed with pembrolizumab-induced adrenal insufficiency with rapid resolution of his symptoms after starting hydrocortisone. His surgery course was smooth, and he received DOS stress-dosed steroids.

Discussion: Syncope can be a very challenging entity in both the outpatient and inpatient setting. Reports of syncope in the preoperative setting must focus its very broad differential on pathologies that also carry an association with increased perioperative risk. Emphasis on cardiac evaluations often supersedes assessment for other organ system pathology. With the heavy emphasis on cardiac assessment in the preop setting, preop clinicians run the risk of anchoring on ruled in or ruled out cardiac pathology yet need to maintain a broad and non-cardiac differential diagnosis list. Similarly, fatigue is a challenging outpatient symptom to evaluate and similarly carries a broad differential applicable to the periop risk evaluation setting including anemia, cardiac or thyroid disease as well as deconditioning and frailty. Screening protocols for adrenal insufficiency for patients on pembrolizumab vary, and perioperative clinicians must remain aware of the inherent risk of this medication as well as the potential for no antecedent screening for endocrine complications of the therapy.

Conclusions: Preoperative clinicians should have a very low threshold of suspicion to evaluate for pembrolizumab-induced adrenal insufficiency in the preoperative setting.