Impact of Levothyroxine Therapy on Lipid Profile Value in Patients of Subclinical Hypothyroidism

INTRODUCTION

The term “subclinical hypothyroidism” is used to describe a state where there is a raised TSH concentrate with a normal concentration of T4. It is common with a prevalence of 7–8% in women and 2–4% in men.¹ Patients with subclinical thyroid disease have a few or no symptoms or signs of thyroid dysfunction and vary in nature, thus, subclinical thyroid disease is a laboratory diagnosis. Levothyroxine therapy in mild elevation of serum TSH is generally agreed to be appropriate.^2,3 Management of patients with a serum TSH level of less than 10 mIU/L is also controversial.⁴ HMG coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol synthesis. In the hypothyroid state, HMGCR mRNA levels are reduced and treatment with thyroid hormone restores it to normal level. Thyroid hormone stimulates HMGCR transcription and increases its stability.⁵ The abnormality of lipid profiles in subclinical hypothyroidism may be related to gradually decreased thyroid hormone (TH) levels in the serum and tissues.⁶ Additionally, high TSH level stimulates HMGCR expression by stimulating the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-responsive element binding protein (cAMP/PKA/CREB) cassette.⁷ Conversion of cholesterol into bile acids is important for maintaining whole body cholesterol homeostasis. The rate-limiting enzyme in bile acid synthesis is controlled by cholesterol 7-hydroxylase which is regulated by thyroid hormone.⁸

Thus, TH also reduces cholesterol through enhancing cholesterol clearance pathway. Over time, the subclinical may develop to overt hypothyroidism. This study will also help patients prevent in the development of overt hypothyroidism

MATERIALS AND METHODS

A randomized control trial, prospective study conducted on 22 cases of subclinical hypothyroidism with 22 control at the Downtown Hospital, Guwahati.

RESULTS

About 22 patients and 22 control were taken in the study. The mean age of patients were 43.22 years and 40.45 years of control. Among cases, the female predominance was 86.36%. The mean value of variables (Table 1) was compared with control (Table 2) after levothyroxine therapy. The mean TSH value was significantly higher, i.e. 7.24 than control i.e. 2.67 after levothyroxine therapy (p value = 0.00091). There was no significant change in the T3 value when compared with control (p value = 0.165746) and T4 value (p value = 0.967266). The mean total cholesterol levels were significantly higher in patients with SH as compared to controls (372.1364 vs 205.5909, p value = <0.0001). The mean LDL levels were reduced from 97.4545 to 85.2727 and the mean VLDL value is decreased from 28.2273 to 27.8636 and is statistically significant when compared with control, p value = 0.003102. The mean triglyceride value decreased from 169.8636 to 166.9545 and is statistically significant when compared with the control, p value < 0.00001. The mean HDL value is increased from 34.7727 to 35.2273 and is statistically significant when compared with the control, p value < 0.00001.

The statistical significance between pretreatment and posttreatment values is found to be in values of TSH, cholesterol, HDL, HDL, LDL, and triglyceride, p < 0.05 (Table 3). There was no significant difference in the pretreatment and posttreatment T3 and T4 values. There was a mild increase in the value of HDL and a significant decrease in the value of TSH, cholesterol, VLDL, and triglyceride.

DISCUSSION

The Colorado study, which screened 25,862 subjects, found that the mean total cholesterol and LDL cholesterol progressively increased with increasing levels of serum TSH and hypercholesterolemia was associated with mild elevations of TSH levels.⁹ In this study, the mean age of patient is 43.22 years which is similar to Rigdway:¹⁰ 44 years, Bell:¹¹ 42 years, and Elder:¹² %3E;40 years. Female predominance in this study 86.36% which is close to study by Bandyopadhyay et al.¹³ where females constituted 78% of study populations. In this study, the mean total cholesterol levels were significantly higher in patients with subclinical hypothyroidism supported by Asranna et al.¹⁴ and Bandyopadhyay et al.¹³ An increased level of LDL and hypertriglyceridemia has been shown to increase the risk of cardiovascular disease. In this study, mean LDL, VLDL, and triglyceride levels were reduced after levothyroxine therapy but only a decreased value of VLDL and triglyceride was statistically significant (p value < 0.05). There was a reduction in the LDL value but this might be due to the presence of confounding factor like low-fat diet intake. Subclinical hypothyroidism was associated with raised LDL levels and, thus, had larger cardiovascular risk (Bakker et al.)¹⁵ and reduced level seen with levothyroxine therapy (Meier et al.).¹⁶ The value of triglyceride is reduced after levothyroxine therapy in this study which is statistically significant. A similar reversal of changes following treatment has shown by Atthans et al.¹⁷ and Monzani et al.¹⁸ A mild increase in the HDL value is also observed which is statistically significance.

There is an increasing prevalence of cardiovascular morbidity. Even a small decrease in the levels of T. cholesterol, LDL, and triglyceride levels results in substantial reductions in cardiovascular morbidity.

CLINICAL SIGNIFICANCE

Levothyroxine therapy is patients of subclinical hypothyroidism reduces the TSH level and, thus, preventing conversion to overt hypothyroidism and also reduces cardiac morbidity.

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