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Hypertriglyceridemia: Differential Diagnoses & Workup

Author: Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Contributor Information and Disclosures

Updated: Jul 12, 2008

Differential Diagnoses

Other Problems to Be Considered

When triglycerides are noted to be elevated, a fasting blood sugar should always be checked to rule out one of the most frequent causes of hypertriglyceridemia, uncontrolled diabetes.  Management of this condition may make medication to lower the triglycerides unnecessary or, at least, easier to normalize. 

A diet high in refined carbohydrates can cause hypertriglyceridemia. While cakes, candy, cookies, etc. are an obvious source, the quantity of liquid calories (nondiet soda, juice, alcohol) should be determined.

Workup

Laboratory Studies

  • Lipid analysis  
    • Elevated triglycerides are determined by direct laboratory analysis of serum or plasma after a 10- to 12-hour fast. Determining which lipoprotein abnormality is the cause of hypertriglyceridemia is less straightforward.
    • VLDLs are increased and chylomicrons are absent when triglyceride levels are elevated but below 1000 mg/dL. If triglyceride levels are above 1000 mg/dL, both VLDL and chylomicrons are usually present.
    • If the triglycerides are elevated but less than 1000 mg/dL and the total cholesterol is elevated, the lipoprotein abnormality may be caused by either (1) elevations of both LDL and VLDL, which is type IIb or mixed hyperlipoproteinemia, or (2) increased remnant VLDL or IDL, which is type III hyperlipidemia or dysbetahyperlipoproteinemia.
    • The 2 disorders may be distinguished by obtaining a direct LDL-c analysis, which is available at most commercial laboratories. If the direct LDL-c is significantly lower than the calculated LDL-c, a diagnosis of type III hyperlipoproteinemia is likely.
    • The only procedure that reliably distinguishes between a mixed hyperlipoproteinemia (increased LDL-c and triglycerides) and type III hyperlipoproteinemia (increased IDL) is beta quantification. This expensive analysis involves ultracentrifugation followed by electrophoresis. It is not performed by most commercial or hospital laboratories. Specialized lipid centers, such as those at Tufts and JohnsHopkinsMedicalCenters, should be contacted if type IIb or III must be confirmed. In most clinical settings, however, distinguishing between these entities is rarely necessary because the treatment of both conditions is essentially the same. Diet modification, exercise, and appropriate weight loss improve both. Type IIb and III also  respond to the same medications—niacin and/or fibric acid derivatives.7 Therefore, no matter which diagnosis applies to a given patient, the treatment is the same.
  • Chylomicron determination
    •  If the triglyceride levels are greater than 1000 mg/dL and the presence of chylomicrons must be confirmed, the simplest and most cost-effective test involves overnight refrigeration of a tube plasma or serum.
    • If chylomicrons are present, simple inspection reveals a creamy layer overlying either cloudy or clear serum.
    • If the infranatant is cloudy, high levels of VLDL are present (type V hyperlipidemia).
    • If the infranatant is clear, the VLDL content is normal and type I hypercholesterolemia (elevated chylomicrons only) should be suspected.
  • Type I hyperlipoproteinemia (pure hyperchylomicronemia)
    • To make a definitive diagnosis of type I hypercholesterolemia, deficiency of either LPL or apo C-II must be confirmed. The presence of LPL activity may be measured in plasma following intravenous heparin administration (50 IU of heparin per kg body weight) or by analysis of muscle or adipose tissue biopsy samples.
    • Defective or absent apo C-II must be determined at a lipid center that performs 1 of the 3 following assays: (1) gel electrophoresis, (2) radioimmunoassay, or (3) confirmation that LPL added to the patient's plasma is not active.

Other Tests

Rule out secondary causes of hypertriglyceridemia, including diabetes mellitus and hypothyroidism.

Procedures

If the diagnosis of eruptive xanthomas is in doubt, obtaining a biopsy of the suspicious lesions will reveal accumulations of fat (not cholesterol).

More on Hypertriglyceridemia

Overview: Hypertriglyceridemia
Differential Diagnoses & Workup: Hypertriglyceridemia
Treatment & Medication: Hypertriglyceridemia
Follow-up: Hypertriglyceridemia
Multimedia: Hypertriglyceridemia
References
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Further Reading

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Keywords

hTG, chylomicronemia, dysbetalipoproteinemia, familial combined hyperlipoproteinemia, hyperlipidemia, hyperlipoproteinemia, mixed hyperlipidemia, type I hyperlipoproteinemia, type IIb hyperlipoproteinemia, type III hyperlipoproteinemia, type IV hyperlipoproteinemia, type V hyperlipoproteinemia, triglycerides, diabetes mellitus, DM, coronary artery disease, CAD, cardiovascular disease, CVD

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Contributor Information and Disclosures

Author

Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Steven R Gambert, MD, Program Director, Physician-in-Chief, Professor, Department of Internal Medicine, Sinai Hospital, Johns Hopkins University School of Medicine
Steven R Gambert, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Yoram Shenker, MD, Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison
Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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