Case Presentation: A 72 year old woman with a history of recurrent, metastatic breast cancer complicated by pembrolizumab-related immune-mediated colitis presented to our hospital with sudden onset dizziness and shortness of breath. Four weeks prior to presentation, she suffered a colitis flare and was treated with a rapid 40 mg prednisone taper along with dapsone for Pneumocystis jirovecii pneumonia (PJP) prophylaxis. On presentation to the emergency room, the patient was noted to be hypoxic to 86% while breathing ambient air; she was otherwise hemodynamically stable. Computed tomography with administration of intravenous contrast revealed bilateral segmental pulmonary emboli (PE), with laboratory studies only notable for normal cardiac biomarkers. A bedside echocardiogram did not show evidence of right heart strain. The patient was started on enoxaparin and admitted for further management. Over 24 hours, the patient had two episodes of hypotension that improved with intravenous fluid administration. There was no evidence of right heart strain on repeated point-of-care ultrasound or cardiac biomarker testing. At this point, our team took a diagnostic time out to re-evaluate our differential diagnosis. A morning serum cortisol was added to morning labs already drawn and found to be 3.0 mcg/dL. She became increasingly hypoxic despite escalation to high flow nasal cannula. She was noted to have cyanotic lips with a dark arterial blood sample. Arterial blood gas sampling revealed elevated PaO2 of 253 mmHg. A methemoglobin level was obtained and found to be 13.8%. Dapsone was held with resolution of the patient’s peripheral hypoxemia and methemoglobinemia. The patient was started on stress-dose hydrocortisone for suspected secondary adrenal insufficiency and her hypotension resolved. The patient had a reported atovaquone allergy, but tolerated an oral atovaquone challenge. She was discharged on rivaroxaban, a prednisone taper, and atovaquone for PJP prophylaxis.
Discussion: In hospital medicine, our first encounter with a patient is oftentimes in the setting of a predetermined diagnosis. This can make us vulnerable to anchoring bias, particularly in clinical situations where the presentation may not closely align with the supposed diagnosis. The concept of a diagnostic time out has been previously described in the literature. It joins other recommended practices meant to avoid heuristic bias in the diagnostic evaluation of our patients. Bilateral segmental PE was a convincing diagnosis in this patient with dyspnea and hypoxemia given her known malignancy with likely hypercoagulability. However, her recurrent hypotension and unresponsiveness to oxygen supplementation were out of proportion to the clinical findings given no right heart strain or elevated cardiac markers. This incongruity and her history of chronic dapsone and steroid exposure prompted a diagnostic time out and re-assessment of our differential diagnosis. This prompted our evaluation for methemoglobinemia and secondary adrenal insufficiency.
Conclusions: Our presentation of a case of methemoglobinemia and secondary adrenal insufficiency in a patient found to have bilateral segmental pulmonary embolisms highlights the importance of a diagnostic time out to avoid anchoring bias. This practice is useful as part of a routine assessment of a diagnosis, but is of greater significance in cases where the presentation appears incongruent with the leading diagnosis.