Hypercholesterolemia and anorexia

I saw a thin young woman with chronic weight loss to rule out adrenal insufficiency or other endocrine disorder. Her morning cortisol was high normal, adrenocorticotropic hormone was normal, and thyroid studies were optimal. Evaluation for celiac or other gastrointestinal malabsorptive disorders was negative. There was no reason to suspect central adrenal insufficiency. However, she had been amenorrheic for years. Synthetic ACTH testing demonstrated a robust response ruling out adrenal insufficiency.

The most striking laboratory abnormality was her lipid profile. The total cholesterol was 311 mg/dL, triglycerides 46 mg/dL, HDL 82 mg/dL and LDL 224 mg/dL. She denied history of hypercholesterolemia. There was no family history of severe hypercholesterolemia or premature cardiovascular disease. Additional studies did not reveal any causes of secondary dyslipidemia.

She had mentioned a previous diagnosis of anorexia nervosa but said it was no longer a problem. When I questioned her more directly about this, she admitted to avoiding food and eating sparingly because she did not feel hungry.

Hypercholesterolemia has long been known to be associated with anorexia nervosa. Typically total cholesterol and LDL are elevated; HDL may be high also. With refeeding, cholesterol levels return to baseline. Other forms of malnutrition are not usually associated with high cholesterol. However, until recently the underlying mechanism has not been clearly delineated. A PubMed search revealed only a handful of articles reviewing hypercholesterolemia due to anorexia.

There have been several theories regarding the pathophysiology. These include reduced cholesterol metabolism, starvation-induced increased flux of peripheral cholesterol to the liver, decreased LDL-receptor activity and/or decreased triiodothyronine associated with a starvation state.

Our current understanding is that the hypercholesterolemia is due to increased cholesterol ester transfer protein (CETP) activity in patients who are malnourished but have preserved levels of free fatty acids. In contrast to normal controls and individuals with hypothyroidism, patients with anorexia have higher levels of CETP. Patients who binge have higher cholesterol than those with the purely restrictive form. Those with more severe malnutrition and the lowest BMI often have low rather than high cholesterol.

I found little published regarding potential cardiovascular risk associated with hypercholesterolemia due to anorexia. Given the transient nature and rapid improvement with refeeding, high HDL levels and otherwise low cardiovascular risk of the population most commonly afflicted with eating disorders, I would be surprised if it were elevated. Still, it would be interesting if this population were studied prospectively over the long term regarding this issue.

Rigaud D. Diabete Metab. 2009;35:57-63.

Ohwada R. Int J Eat Disord. 2006;39:598-601.