What is the relationship between thyroid hormone and cholesterol levels?

Relationship Between Thyroid Hormone and Cholesterol Levels

Thyroid hormones play a critical role in regulating cholesterol metabolism, with hypothyroidism causing increased serum cholesterol levels (particularly total cholesterol, LDL cholesterol, and triglycerides) and hyperthyroidism causing decreased cholesterol levels. 1

Thyroid Hormone Effects on Lipid Metabolism

Hypothyroidism and Cholesterol

• Hypothyroidism is strongly associated with dyslipidemia, characterized by:
  • Increased total cholesterol
  • Elevated LDL cholesterol
  • Higher triglyceride levels
  • Potential increase in HDL cholesterol 1, 2

The relationship is dose-dependent, with more severe hypothyroidism typically causing more pronounced lipid abnormalities. Even subclinical hypothyroidism (elevated TSH with normal free T4) can cause lipid alterations, though the evidence is less consistent than with overt hypothyroidism 2, 3.

Hyperthyroidism and Cholesterol

• Hyperthyroidism has the opposite effect:
  • Decreased total cholesterol
  • Reduced LDL cholesterol
  • Potentially lower HDL cholesterol 1, 4

Mechanisms of Action

Thyroid hormones regulate cholesterol metabolism through several mechanisms:

1. Cholesterol synthesis regulation: Thyroid hormones stimulate cholesterol synthesis, but their overall effect is to lower serum cholesterol through enhanced clearance mechanisms 4

2. LDL receptor expression: Thyroid hormones increase LDL receptor expression in the liver, enhancing LDL cholesterol clearance from circulation 3

3. Bile acid production: Thyroid hormones may enhance conversion of cholesterol to bile acids, though human studies have not consistently demonstrated this effect 4

4. Lipoprotein metabolism: Thyroid hormones affect various aspects of lipoprotein metabolism, including VLDL production and HDL metabolism 3

Clinical Implications

Screening Recommendations

• Thyroid function should be assessed in patients with unexplained dyslipidemia 1
• TSH is the most sensitive initial test for detecting thyroid dysfunction

Treatment Effects

• Treatment of hypothyroidism with levothyroxine typically improves lipid parameters:
  • Reduces total cholesterol
  • Lowers LDL cholesterol
  • Decreases triglycerides
  • May reduce lipoprotein(a) levels 5

The improvement in lipid profile after achieving euthyroid status may reduce cardiovascular risk in patients with hypothyroidism 2.

Cardiovascular Risk Assessment

• Untreated hypothyroidism increases cardiovascular disease risk partly through elevated LDL cholesterol 1
• The relationship between TSH and lipid profile appears to be continuous, with no clear threshold for association 6
• Even within the euthyroid range, variations in thyroid hormone levels can affect lipid parameters 7

Common Pitfalls and Considerations

• Overlooking thyroid dysfunction: Failing to check thyroid function in patients with unexplained dyslipidemia can lead to missed diagnoses 1

• Interpretation challenges: Non-thyroid illness can affect TSH results and complicate interpretation 1

• Subclinical hypothyroidism: The impact on lipids may be more subtle but still clinically relevant, especially with TSH levels >10 mIU/L 2

• Monitoring: After initiating thyroid hormone replacement, lipid profiles should be reassessed once euthyroid status is achieved 1

• Medication interactions: Some lipid-lowering medications may affect thyroid hormone absorption, requiring monitoring and potential dose adjustments