What is the relationship between thyroid function and cholesterol levels?

Relationship Between Thyroid Function and Cholesterol Levels

Thyroid dysfunction significantly impacts cholesterol metabolism, with hypothyroidism causing increased total and LDL cholesterol levels, while hyperthyroidism typically leads to decreased cholesterol levels. 1, 2

Thyroid Hormones and Lipid Metabolism

• Thyroid hormones play a crucial regulatory role in cholesterol production, transformation, and clearance throughout the body 1
• In normal thyroid function, thyroid hormones help maintain healthy cholesterol levels by regulating hepatic LDL receptors and various enzymes involved in lipid metabolism 2
• Both TSH and thyroid hormones themselves participate in lipid regulation, with genetic studies confirming a causal relationship between thyroid function and lipid levels 3

Effects of Hypothyroidism on Cholesterol

• Overt hypothyroidism is characterized by hypercholesterolemia with marked increases in LDL cholesterol and apolipoprotein B 2
• The primary mechanism involves decreased fractional clearance of LDL due to reduced LDL receptors in the liver 2
• A one standard deviation increase in genetically predicted TSH levels is associated with a 0.037 SD increase in total cholesterol levels and 0.026 SD increase in LDL cholesterol 3
• HDL levels may be normal or even elevated in severe hypothyroidism due to decreased activity of cholesteryl-ester transfer protein (CETP) and hepatic lipase (HL) 2
• Hypothyroidism increases oxidation of plasma cholesterol, creating additional cardiovascular risk 2

Effects of Subclinical Hypothyroidism on Lipids

• Subclinical hypothyroidism (elevated TSH with normal T4) is associated with lipid abnormalities including normal or slightly elevated total cholesterol, increased LDL, and lower HDL 2
• Evidence on treatment effects is mixed - in 8 trials (n=597), only 3 showed statistically significant improvements in lipid profiles with levothyroxine treatment 4
• When significant, treatment differences ranged from -0.7 to 0 mmol/L (-28 to 0 mg/dL) for total cholesterol and -0.6 to 0.1 mmol/L (-22 to 2 mg/dL) for LDL cholesterol 4
• No studies reported statistically significant differences in HDL cholesterol or triglyceride levels with treatment 4

Effects of Hyperthyroidism on Cholesterol

• Hyperthyroidism leads to enhanced excretion of cholesterol and increased turnover of LDL 2
• This results in decreased total and LDL cholesterol levels 2
• HDL levels are typically decreased or not significantly affected in hyperthyroidism 2

Clinical Implications

• Thyroid function should be evaluated in patients with unexplained dyslipidemia, as treating underlying thyroid dysfunction may improve lipid profiles 1, 2
• Thyroxine therapy in appropriate doses usually leads to considerable improvement in lipid profiles in hypothyroid patients 2
• The relationship between TSH and lipids appears to have no clear cutoff threshold, suggesting a continuous relationship 5
• Subclinical hypothyroidism has been associated with endothelial dysfunction, aortic atherosclerosis, and increased myocardial infarction risk, possibly related to lipid abnormalities 2

Important Considerations and Pitfalls

• TSH levels can vary by up to 50% day-to-day, with 40% variation even at the same time of day, making serial measurements essential 4, 6
• A single abnormal TSH value is insufficient to establish thyroid dysfunction; confirmation with repeat testing is necessary 4
• When interpreting thyroid function tests in relation to lipids, consider that medications, acute illness, pregnancy, and other conditions can affect TSH levels 4
• While treatment of subclinical hypothyroidism may improve lipid profiles, it remains unclear whether these changes translate to reduced cardiovascular morbidity or mortality 4
• Individual variability in lipid responses to thyroid dysfunction is considerable 2

Emerging Research

• Thyromimetics represent a potential new class of hypolipidemic drugs that may improve lipid profiles while potentially accelerating energy expenditure 5
• Recent Mendelian randomization studies provide stronger evidence for causal relationships between thyroid function and cardiovascular risk factors including cholesterol levels 3
• The lowest quartile of normal FT4 levels is associated with 1.3 times higher risk of metabolic syndrome compared to the highest quartile, suggesting that even variations within the normal range may be clinically relevant 7