PROSTATE LACTATE: A CASE OF SEVERE LACTIC ACIDOSIS WITH AN INTERESTING MECHANISM OF ACTION

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: In the era of the surviving sepsis campaign, there is mounting pressure for early detection and escalation of care for patients with sepsis and septic shock; obtaining serum lactate is recommended in the Hour-1 Bundle as an early indicator of inadequate tissue perfusion from shock. However, there are many other causes of lactic acidosis that are often overlooked during the initial evaluation. We present a rare case of severe lactic acidosis due to metastatic prostate cancer and the Warburg Effect. CASE PRESENTATION: An 85-year-old man with prostate cancer, coronary artery disease, and atrial fibrillation was admitted with two days of fatigue and generalized weakness. He was hemodynamically stable but initial labs revealed a serum lactate of 9.2 mmol/L, triggering the hospital’s “Sepsis Bundle” and leading to transfer to the Intensive Care Unit. Fluid resuscitation and empiric antibiotics were started with blood cultures later positive for sensitive enterococcus faecalis. After resolution of his bacteremia, the lactate level remained elevated at 6-9 mmol/L, and transiently increased to 20 mmol/L following a ureteral stent exchange, despite normal blood pressures and urine output and warm, dry skin. There was no reported history of metformin use or other toxic etiology. Cross-sectional imaging obtained to evaluate for localized tissue ischemia only showed progression of his metastatic prostate cancer with diffuse lymphadenopathy and osseous metastases. No liver metastases were identified. The persistent, severe lactic acidosis was thought to be due to metastatic prostate cancer and the patient elected to focus on comfort care. DISCUSSION: With increased emphasis on early detection of sepsis, serum lactate has become a common marker of inadequate tissue perfusion. However, clinicians must also consider other causes to include mitochondrial dysfunction, severe liver disease, and medications. More rarely, it can be caused by cancer, most commonly leukemia and lymphoma, but also some solid malignancies. Multiple mechanisms have been proposed to include impaired lactate metabolism and clearance due to liver metastases as well as the Warburg Effect, which is the likely etiology in this case. First described in 1920, it describes how cancer cells have increased glucose uptake with preferential use of glycolysis, leading to increased lactate production, even in the presence of adequate oxygen and functioning mitochondria. Unfortunately, the only therapeutic option is treatment of the underlying malignancy and both patients died in the only two other case reports of prostate cancer related lactic acidosis. CONCLUSIONS: With increased utilization of serum lactate levels, being mindful of the broad differential is critical in addressing the underlying cause. Providers should exercise pause when treating patients with elevated lactate who are hemodynamically stable without evidence of poor perfusion. Reference #1: Munoz J, Mohd K, Amr H, Stoltenberg M. Severe lactic acidosis in a patient with metastatic prostate cancer. J Can Res Ther. 2011;7:201-2. Reference #2: Van der mijn JC, Kuiper MJ, Siegert CEH, Wassenaar AE, Van noesel CJM, Ogilvie AC. Lactic Acidosis in Prostate Cancer: Consider the Warburg Effect. Case Rep Oncol. 2017;10(3):1085-1091. Reference #3: Vander heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029-33. DISCLOSURES: No relevant relationships by Kimberly Fabyan, source=Web Response No relevant relationships by Arthur Holtzclaw, source=Web Response No relevant relationships by John Sherner, source=Web Response