Abstract
There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a retrospective cohort study using Longitudinal Health Insurance Database (LHID) from Taiwan, R.O.C. We also evaluate the influence of 6-n-propyl-2-thiouracil (PTU) and methimazole (MMI) on hepatic genes to explain changes in blood lipid levels in a hepatic cell line model. The cohort study involved 13,667 patients with hyperthyroidism, and the corresponding comparison cohort had four times as many patients. Using Kaplan-Meier analysis method, the results showed that, compared to patients without hyperthyroidism, the overall incidence of hyperlipidemia was significantly higher in the hyperthyroidism patients (18.7 vs. 11.8 cases/1,000 persons-years; adjusted HR 1.5; 95% CI, 1.41–1.59). With only PTU or MMI/carbimazole (CBM) treatment, patients with hyperthyroidism showed a 1.78-fold (95% CI, 1.50–2.11) and 1.43-fold (95% CI, 1.27–1.60) higher risk of hyperlipidemia than those without hyperthyroidism, respectively. Additionally, hyperthyroidism patients that received surgery only or surgery with I131 therapy tended to have a higher risk of hyperlipidemia. Although PTU and MMI treatment decreased the expression levels of genes responsible for circulating remnant lipoproteins, they increased the levels of lipogenic gene expression in hepatic cells. Thus, treatment of hyperthyroid patients with anti-thyroid drugs (ATDs), I131, or surgery is likely to induce hyperlipidemia. ATDs downregulate the expression of genes involved in lipoproteins clearance; increases lipogenic genes expression, which may partly contribute to abnormal blood lipid profiles.
Highlights
Thyroid is an important organ involved in the regulation of various cellular processes such as cell proliferation and development, control of resting metabolic rate, thermoregulation, and metabolism of carbohydrates, proteins, and lipids [1]
We investigated the correlation between hyperthyroidism and hyperlipidemia in patients under treatments and our study can be summarized in the following major points: [1] this was a nationwide population-based cohort study that comprehensively surveyed the possible association between hyperthyroidism and the development of hyperlipidemia under the anti-thyroid drugs (ATDs), I131, and surgery therapy; [2] after treatment with ATDs, the incidence of hyperlipidemia was higher in patients with hyperthyroidism than in patients without hyperthyroidism; [3]
We investigated the effect of PTU and MMI treatment on the expression of gene expression of hepatic LDL receptorsrelated protein 1 (LRP1), hepatic lipase (HL), lipoprotein lipase (LPL), and cholesteryl ester transfer protein (CETP)
Summary
Thyroid is an important organ involved in the regulation of various cellular processes such as cell proliferation and development, control of resting metabolic rate, thermoregulation, and metabolism of carbohydrates, proteins, and lipids [1]. Dysfunction of thyroid affects appetite, body weight, muscle mass, as well as brings about changes in the adipose tissue by altering lipolysis, resulting in increased incidences of insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) [2]. It has been shown that patients with thyroid dysfunction have significantly altered lipids profiles. Hypo- and hyperthyroidism are two of the most common diseases of the thyroid gland. Hyperthyroidism is a prevalent endocrine disorder, which is characterized by excessive secretion of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4) [1]. Graves’ disease (GD) is an organ-specific autoimmune disorder that is caused by thyroid stimulatory immunoglobulins and it represents the most common type of hyperthyroidism [3]. The autoantibodies produced imitate the thyroid stimulating hormone (TSH) and lead to stimulation of thyroid function and suppress the TSH levels while elevating serum free T4 and T3 levels
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