Is hypothyroidism associated with hypertriglyceridemia?

From the Guidelines

Yes, hypothyroidism is associated with elevated triglyceride levels, as stated in the 2019 guideline by the American College of Cardiology/American Heart Association task force on clinical practice guidelines 1. Patients with an underactive thyroid often experience lipid abnormalities, including increased triglycerides, elevated total cholesterol, and higher LDL cholesterol levels. This occurs because thyroid hormones play a crucial role in lipid metabolism by regulating the expression of genes involved in lipid synthesis and clearance. In hypothyroidism, there is decreased activity of lipoprotein lipase, an enzyme responsible for breaking down triglycerides, as well as reduced clearance of triglyceride-rich lipoproteins from the bloodstream. Additionally, hypothyroidism leads to decreased expression of LDL receptors in the liver, impairing cholesterol removal from circulation. Some key points to consider in the management of hypertriglyceridemia include:

• Evaluating patients for secondary causes of hyperlipidemia, such as hypothyroidism, and treating them accordingly 1
• Assessing patients for other cardiovascular risk factors, such as central obesity, hypertension, abnormal glucose metabolism, and liver dysfunction
• Initial treatment of patients with mild to moderate hypertriglyceridemia should include dietary counseling and weight loss in patients who are overweight or obese Treatment of the underlying thyroid condition with levothyroxine (typically starting at 25-50 mcg daily and titrating based on TSH levels) often improves the lipid profile, including triglyceride levels. However, some patients may require additional lipid-lowering therapy if their triglycerides remain elevated despite achieving normal thyroid function. It is essential to address and treat lifestyle factors, secondary factors, and medications that increase triglycerides, as recommended in the 2019 guideline 1.

From the Research

Association between Hypothyroidism and Triglyceride Levels

• Hypothyroidism is closely associated with increased serum triglyceride (TG) levels, as well as total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) 2.
• The thyroid gland plays a crucial role in modulating cholesterol production, transformation, and clearance, with thyroid hormones (THs) regulating these processes 2.
• Down-regulated THs and up-regulated thyroid-stimulating hormone (TSH) in serum are associated with the pathologic development of hypothyroidism-related hyperlipidemia, including elevated triglyceride levels 2.

Mechanisms underlying the Association

• Thyroid dysfunction, including hypothyroidism, negatively affects lipid metabolism, leading to hypercholesterolemia and increased risk of cardiovascular disease 3.
• The reduction in low-density lipoprotein (LDL) receptor activity and diminished control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2) contribute to hypercholesterolemia in hypothyroidism 3.
• Thyroid hormone administration may reverse the dyslipidemic profile commonly occurring in hypothyroidism, including elevated triglyceride levels, although the potency of the effects may be age- and sex-dependent 3.

Clinical Implications

• Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis 4.
• Guidelines for the management of severe hypertriglyceridemia recommend immediate use of triglyceride-lowering agents, while statins remain the first line of therapy for mild to moderate hypertriglyceridemia 4.
• Subclinical hypothyroidism has been associated with risk factors for cardiovascular disease, including hypertension and dyslipidemia, although the use of levothyroxine to reduce CVD risk is not clearly beneficial 5.