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
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.