Extreme hypertriglyceridaemia

Plasma triglyceride concentrations in excess of 10 mmol/l should be considered extreme. At these concentrations plasma is usually turbid and at very extreme concentrations (30-100 mmol/l) the volume in plasma taken up by the lipid fraction is so much increased as to cause water displacement, giving rise to pseudohyponatremia. Typical clinical signs are lipaemia retinalis and occasionally eruptive xanthomata which are seen as small maculopapular red skin lesions. When these signs are present acute pancreatitis is imminent and immediate safe reduction in plasma triglyceride concentrations is essential.

Pathogenesis

Triglycerides in plasma are carried by chylomicrons, chylomicron remnants and very low density lipoproteins. Hypertriglyceridaemia does not usually become extreme unless there is a triglyceride catabolic defect. Although clearance of triglycerides is conveyed by a singly enzyme (LPL, lipoprotein lipase), the regulation of this enzyme is such that failing function of multiple other proteins, such as APOA5, GPIHBP1 and APOC2 can simulate partial or total LPL deficiency.

Mutations in the genes encoding for all these proteins have been associated with hypertriglyceridaemia. However, unless there is a known complete absence of LPL activity, such as in familial chylomicronaemia or Frederickson’s Type I hyperlipidaemia, the hypertriglycerideamia rarely becomes extreme unless there is an obvious precipitating factor. Poorly controlled diabetes, obesity, lipodystrophy, hypothyroidism, excessive alcohol consumption are all known precipitating factors.

If the cholesterol concentrations is drastically (to more than ~12 mmol/l), together with the raised triglycerides, dysbetalipoproteinamia or Frederickson’s type III hyperlipidaemia should be suspected. A typical clinical sign for this would be tuberoeruptive xanthomata and orange creases in the palm of the hands. Again, the same precipitating factors should be considered.

Complications

The risk of acute pancreatitis is imminent if the triglyceride concentration is greater than 20 mmol/l. Drastically raised triglycerides are probably not closely associated with atheromatous disease.

Management

In the acute setting, it is most important to eliminate dietary fat as far as possible. This eliminates the intestinal secretion of chylomicrons and the plasma triglyceride concentrations will drop rapidly (within days to a week). On a theoretical basis it has been suggested to use more active approaches, such as glucose-insulin infusions, but the efficacy of this is not clear. Clearing triglycerides from the blood plasmapheresis is possible but obviously of little value unless chylomicron production is also eliminated. Long-term treatment involves eliminating the precipitating factors and most often pharmacological triglyceride lowering medication such as fibrates. Nicotinic acid is no longer recommended as a TG-lowering agent. High-dose concentrated fish oil preparations can be used but there is limited evidence in extreme hypertriglyceridaemia.

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