Hypertriglyceridemia

Background

• ~5% of acute pancreatitis caused by high triglycerides
• Etiologies
  • Familial hypertriglyceridemia, autosomal dominant with variable penetrance
  • Secondary forms
    • DM, obesity, EtOH, estrogen therapy
    • Hypothyroidism, ESRD, nephrotic syndrome, HIV, anti-HIV meds
• TG levels > 2000mg/dL almost always have both secondary and genetic form
• 1.7% of US estimated to have [TG] between 500-2000
• May present with normal serum lipase levels

Pathophysiology

• Excess TG hydrolyzed by increased concentration of pancreatic lipase
• Produces increased concentration of free fatty acids that exceeds binding capacity of albumin
• Micelles are formed that attack platelets, vascular endothelium and acinar cells
• Ischemia and pancreatic injury result
• An acidic environment potentiates free fatty acid toxicity

Clinical Features

General

A pediatric patient's knee showing multiple xanthoma tuberosum (i.e. xanthoma located over a joint).

• Most are generally asymptomatic until sequelae present
• Eruptive xanthoma may be found on dermatologic exam

Hypertriglyceridemic Pancreatitis

Signs/symptoms of pancreatitis

• Pain is the most common symptom and is often characterized by:
  • Persistent
  • Localizes to epigastric area, around waist, RUQ, or occasionally LUQ
  • Radiates to back
  • The onset may be less abrupt and the pain poorly localized
• Nausea/vomiting noted in most
• Abdominal distention is frequent complaint
• Cullen sign (ecchymosis of periumbilical region) - intrabdominal hemorrhage
• Turner sign (ecchymosis of flanks) - retroperitoneal hemorrhage
• Pulmonary Findings
  • Hypoxemia, ARDS, tachypnea
  • Indicates severe pancreatitis
    • Diaphragmatic inflammation, pancreatico-pleural fistula

Differential Diagnosis

Epigastric Pain

• Gastroesophageal reflux disease (GERD)
• Peptic ulcer disease with or without perforation
  • Zollinger-Ellison syndrome
• Gastritis
• Pancreatitis
• Gallbladder disease
  • Acute cholecystitis
  • Cholangitis
  • Symptomatic cholelithiasis
  • Acalculous cholecystitis
• Myocardial Ischemia
• Splenic Infarctionenlargement/rupture/aneurysm
• Pericarditis/Myocarditis
• Aortic dissection
• Hepatitis
• Pyelonephritis
• Pneumonia
• Pyogenic liver abscess
• Fitz-Hugh-Curtis Syndrome
• Hepatomegaly due to CHF
• Bowel obstruction
• SMA syndrome
• Pulmonary embolism
• Bezoar
• Ingested foreign body

Evaluation

• Triglycerides; Severely elevated (at least >500 mg/dL, generally >1,000 mg/dL)
  • Lipids in serum may interfere with other lab tests
    • Falsely low Na+, amylase

Pancreatitis workup

• Rule out other causes of pancreatitis (e.g. gallstone pancreatitis)
• In general, if triglycerides >1000, can assume this is cause of pancreatitis
• Lipase level >3x upper limit of normal
  • Sensitivity 82-100%, specificity 82-100%
  • Negative lipase does not exclude pancreatitis in chronic/recurrent disease
  • Absolute value not associated with prognosis or severity
• Characteristic findings on ultrasound or CT

Management

Management of acute pancreatitis in the setting of hypertriglyceridemia

• Evidence for management based on case series and reports
• Insulin drip - most dramatic and rapid intervention, with reduction within 24 hrs
  • Initiate at 0.1 units/kg/hr (similar to treatment for DKA)
  • Goal is to reduce triglycerides to < 500
  • Add D5NS if glucose drops < 200
  • Monitor BMP q2 hr
  • Manage potassium
    • K < 3.2 stop insulin and replete K
    • K 3.3 to 5 add 20 mEq K/Lto IVF
    • K > 5 no extra potassium
• IVF as for standard pancreatitis treatment, add potassium as per above
• Treat concurrent hypothyroidism if present
• Pain control
• Niacin 500mg QD
• Gemfibrozil or fenofibrate
• Max dose statin, 81mg ASA
• Heparin q8 SC, effect short-lived
• NPO initially
• May advance diet starting at TG level < 1000mg/dL with resolution of abdominal pain/pancreatitis symptoms
  • No fat diet
  • Low calorie diet

Plasma exchange

• Therapeutic plasma exchange, for 1-3 days (sickest patients)
  • Generally indicated for hypocalcemia, persistent elevated lactic acidosis, other signs of worsening organ dysfunction
• For euglycemic patients, not routine first line
• Requires central venous access

Disposition

• Asymptomatic hypertriglyceridemia is treated as an outpatient
• For acute pancreatitis, ICU or step-down for frequent labs, insulin drip

See Also

• Acute pancreatitis