Severe Hypertriglyceridemia Causing Pseudo-acidosis: A Case Report

Pseudo hypobicarbonatemia is a rare phenomenon associated with spuriously low bicarbonate levels in the presence of elevated triglycerides (TG). TG’s interfere with commonly used enzymatic assays in basic metabolic panel (BMP), giving falsely low bicarbonate levels. It adds to the diagnostic dilemma and possible extensive workup to identify the cause. Previous case reports have used plasmapheresis in these settings. We report the successful use of insulin infusion in managing a case of pseudo-acidosis secondary to severely high TG levels. Our patient was a 53-year-old female who presented with complaints of progressive fatigue. Her bicarbonate was 5 mmol/L on workup, anion gap was 30 mmol/L, with elevated TG levels (5904 mg/dL). Arterial blood gas analysis showed normal pH (7.32) and normal calculated bicarbonate (22.8 mmol/L). Insulin infusion was started along with adding fenofibrate and atorvastatin. TG levels decreased progressively to 509 mg/dL with an associated normalization of bicarbonate levels and anion-gap acidosis on BMP. The patient was discharged on day 8 of her hospital stay. Hyper TG can lead to pseudo hypobicarbonatemia, presenting as pseudo anion gap metabolic acidosis. It is essential to correlate the lab findings in the perspective of clinical findings to avoid over-testing and clinical misdiagnosis. In addition, these patients can be managed safely with insulin infusion in resource-limited settings.


Introduction
Hypertriglyceridemia (HTG) is associated with the risk of stroke, pancreatitis, and coronary artery disease, especially in young patients. Elevated triglycerides (TG) can alter routine labs, leading to a diagnostic dilemma requiring high clinical suspicion for efficient and accurate diagnosis. Strong family history is often a diagnostic clue. The management of these patients is equally challenging. Few case reports have described the use of plasmapheresis in managing such patients; however, cost-efficiency, invasiveness, and availability may limit its use. We present a 53-year old female admitted with severe HTG levels (> 5000 mg/ dL), serum bicarbonate of 5 mmol/l, anion gap of 30 and managed with insulin infusion.

Case Presentation
The patient is a middle-aged female, who presented to the emergency department with complaints of progressive fatigue, and occasional blurring of vision for 3 weeks. She also complained of nausea and vomiting for the last three weeks. There were no additional complaints.
The patient's past medical history was significant for type 2 diabetes mellitus on metformin, diagnosed at 35 years of age. The last HbA1c, 4 months prior to presentation, was 7.1. The patient also had a history of hypercholesterolemia, diagnosed ten years back, on atorvastatin 20 mg, which was increased to 80 mg 4 months prior to admission.
She also had hypertriglyceridemia (HTG), which was progressively worsening. Before admission, the last lipid level showed cholesterol of 883 mg/dL, TG 5336 mg/ dL, and very low HDL. Other history was significant for hypertension, hypothyroidism, asthma, chronic tobacco use, and bipolar disorder. She had a positive family history of high triglycerides and lipids in her grandfather and paternal uncle but she is unaware of the type and severity of hyperlipidemia. She did endorse having a fat-rich diet including regular consumption of cream cheese, cookies, chips, pizzas, and beef. She has at least four cups of coffee, with 44 oz. of diet soda daily.
The patient's weight was 113 kg, height was 162.6 cm, and body mass index (BMI) was 42.76 kg/m 2 at the presentation time. Vital signs included a blood pressure of 202/95 mmHg, a pulse of 89 bpm, respiratory rate of 18 bpm, a temperature of 97.7° F, and oxygen saturation of 97% on room air. Physical examination was unremarkable. She did not have any hypertriglyceridemia-associated clinical features.
The patient had hyponatremia, low bicarbonate, and a high anion gap on the metabolic panel. Contrary to that, the patient had a slightly low pH and normal calculated bicarbonate levels on the ABG. The metabolic abnormalities were assumed to be spurious and related to the high TG levels. Her symptoms of fatigue and occasional blurring of vision were attributed to chylomicronemia syndrome. Due to risk of pancreatitis associated with such high TG levels, she was started on insulin infusion at 2U/h, gradually increasing to 7U/h with a strict low-fat diet. Atorvastatin 80 mg and fenofibrate were also added. Patients' triglyceride improved to 1071 on day 7 of hospitalization, measured bicarbonate improved to 23, serum sodium to 141, anion gap to 11. She was subsequently transitioned to subcutaneous insulin on day 7 of her hospital stay and discharged on 20U long-acting insulin twice daily with 6U mealtime insulin on day 8. TG levels at the time of discharge were 1071. On follow-up a month later, the patient was feeling better, and her fatigue had resolved. She complied with her medications, and triglyceride levels had decreased to 506. There were no adverse events on the follow-up.

Discussion
Triglyceride levels below 150 mg/dL are considered normal. High triglyceride levels > 150 mg/dL are strongly associated with cardiovascular disease. With further increases in TG levels, the risk of pancreatitis increases. Severe HTG (> 1000 mg/dL) is associated with a 10-19% incidence of acute pancreatitis [1].
HTG is a common lipid abnormality, but the presentation is generally asymptomatic. They are commonly identified on routine lipid testing. Severely high TG levels can interfere with laboratory testing of sodium, potassium, and chloride ions. The lipemic sample leads to volume displacement reducing the aqueous phase of the sample, giving factitiously low values [2]. Interference with the bicarbonate ions is unusual. Bicarbonate levels are either calculated in the arterial blood gas analysis using the Henderson-Hasselbach equation or measured as total carbon dioxide. TG can affect the measured bicarbonate ions in several ways, by increasing the turbidity in spectrophotometric analyzers as well as an increase in the nonaqueous phase of the sample or partitioning between the polar and nonpolar phases, leading to spuriously low reading of the measured bicarbonate ions, in the setting of a normal bicarbonate ion levels in the ABG, which is calculated and remains unaffected by the laboratory interference. 3 Hence, high TG levels lead to a false impression of increased anion gap metabolic acidosis in a seemingly normal-appearing patient. This can add to  All the cases describing the management of severe hypertriglyceridemia with associated low measured bicarbonate levels have successfully used plasmapheresis [3,4]. However, it is expensive and may not always be available like in our case. We started insulin infusion for our patients while supplementing dextrose in maintenance fluid. Insulin activates lipoprotein lipase and inhibits hormone-sensitive lipase. Lipoprotein lipase metabolizes chylomicrons and very low-density lipoproteins into free fatty acids and glycerol. Therefore, it ultimately decreases serum triglyceride levels [5]. In our patient, with the start of insulin therapy, patient's TG levels started to normalize, and with that, measured bicarbonate levels in her daily BMP started to improve, confirming our diagnosis. One limitation of this case report is that we did not measure apo-E genotype, which could explain the high levels of TGs, especially with the patient's positive family history. Irrespective, this would not have changed the overall treatment.
In conclusion, HTG can lead to pseudohypobicarbonatemia, presenting as pseudo anion gap metabolic acidosis. For physicians, it is essential to correlate the lab findings in the perspective of clinical findings. Moreover, for labs, to possibly red flag such samples and make warning comments making clinicians aware of possible measurement errors.