Is There a Connection Between Hypothyroidism and High Cholesterol?

Written by Nicole Ducharme, DO Endocrinologist

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Hypothyroidism slows metabolism, which compromises how cholesterol is used by the body. But treatments are available to help your levels get back on track.

When someone is affected by hypothyroidism, their metabolism is decreased, including the breakdown of cholesterol and triglycerides. This leads to elevated levels of those fatty substances in the bloodstream, which puts patients at risk of cardiovascular disease.

Thyroid replacement therapy reduces LDL (bad cholesterol), total cholesterol, HDL (good cholesterol), and triglycerides. Here’s how.

How are Hypothyroidism and Cholesterol Connected?

The main role of thyroid hormone is to regulate the body’s metabolism, and therefore it plays an important role in lipid metabolism—the use or storage of fats for energy.

If your metabolism is slowed, which is what occurs in hypothyroidism, the breakdown or elimination of cholesterol is also reduced, which leads to higher circulating cholesterol levels in the bloodstream. These elevated circulating levels then put one at increased risk of cardiovascular disease.

The correlation between hypothyroidism and abnormal cholesterol metabolism was first reported in 1930.¹ Since that time, there has been a gradual recognition of hypothyroidism and its negative impact on cholesterol metabolism, in particular total cholesterol, LDL (bad cholesterol), and triglycerides.

The prevalence of hypothyroidism (marked by elevated TSH and low free T4) and subclinical hypothyroidism (marked by elevated TSH and a normal free T4) is 4.3% and 11.1%, respectively, of hyperlipidemic patients.¹ This indicates that both thyroid hormone and TSH play an integral part in the development of abnormally elevated levels of lipids (fats, cholesterol, triglycerides).

Can Hypothyroidism Cause High Cholesterol Levels?

Yes, hypothyroidism is a secondary cause of high cholesterol levels. The effect of hypothyroidism on lipid metabolism occurs through several different mechanisms due to low T4 and T3 and to the elevation of TSH directly.

Firstly, the LDL receptor is protein that sits on the surface of the liver. Its job is to recognize and take up lipoproteins (certain cholesterol particles) and remove them from the bloodstream. Thyroid hormone serves to increase these receptors.

However, when thyroid hormone is decreased, as it is in hypothyroidism, the number of LDL receptors on the liver surface and the ability to clear out cholesterol are both decreased, which leads to increased cholesterol.

Secondly, the reduction of thyroid hormone also promotes the absorption of cholesterol in the intestine through Niemann-Pick C1-like 1 protein (NPC1L1) and it decreases the breakdown of free fatty acids, which leads to an increase in serum triglycerides.³ In addition, a group of proteins called angiogenin-like proteins (ANGPTL), have been shown to inhibit lipoprotein lipase, an enzyme required to degrade circulating triglycerides.²

Thirdly, there is data that having low T3 levels decreases control of sterol regulatory element-binding protein 2 (SREBP-2), which is essential to activate the LDL receptor.³

More recent data suggests that thyroid hormone may play a role in how bile acids are used by the liver. This process (bile acid synthesis) helps to deplete cholesterol stored in the liver and increase the liver’s uptake of cholesterol from blood circulation. When thyroid hormone is not available, this cannot occur.³

Interestingly, serum concentrations of CETP (cholesteryl ester transfer protein), which plays an important role in suppressing HDL (good cholesterol) levels, has been found to be decreased in patients with hypothyroidism. Therefore, HDL is increased in patients with hypothyroidism.⁵

Not only does a decrease in thyroid hormone lead to the above changes, but the elevation in TSH (independent of thyroid hormone) also stimulates cholesterol production, lipolysis (breakdown of triglycerides into fatty acids released from fat cells into the bloodstream), and a decrease in cholesterol clearance.

Can Levothyroxine Treatment Help to Reduce Cholesterol in Hypothyroidism?

Yes, thyroid replacement has been shown to decrease cholesterol and even normalize cholesterol levels in patients with overt hypothyroidism.

It is not recommended to start treatment in those older than 65 with TSH levels below 10 mlU/L because of the risk of increased mortality with thyroid treatment in this patient population.²

In addition, all patients diagnosed with high cholesterol should have a screening of TSH and free T4 levels before starting treatment.

Can Dietary Changes Reduce High Cholesterol in Hypothyroidism?

The cornerstone of high cholesterol treatment is diet and exercise. However, in patients with secondary hyperlipidemia, such as those with hypothyroidism, diet alone is not likely to significantly decrease cholesterol levels until the underlying disorder is treated.

Therefore, getting the thyroid level into optimal range in those with hypothyroidism is essential to getting cholesterol levels optimally treated.

References:

1. Hixing Liu, Daoquan Peng. Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism. Endocrine Connections. 2022, 11:e210002

2. Xin Su, Hua Peng, Xiang Chen, Xijie Wu, Bin Wang. Hyperlipidemia and hypothyroidism. Clinica Chimica Acta. 2022, 527:61-70

3. Leonidas H. Duntas, Gabriela Brenta. Thyroid hormones: a potential ally to LDL-cholesterol-lowering agents. Hormones. 2016, 15(4):500-510

4. Angeliki Stamatouli, Pablo Bedoya and Sahzene Yavuz. Hypothyroidism: Cardiovascular Endpoints of Thyroid Hormone Replacement. Frontiers in Endocrinology. 2020, 10:1-8

5. Xin Su, Xiang Chen, Hua Peng, Jingjin Song, Bin Wang, Xijie Wu. Novel insights into the pathological development of dyslipidemia in patients with hypothyroidism. Bosn J Basic Med Sci. 2022, 22(3):326-339