Evaluation of serum lipid profile in female patients with hypothyroidism: a rural based study

INTRODUCTION

Hypothyroidism is commonly seen during routine ENT practise. It is more prevelant in women than men by 6 to 8 times and increases with age.^1-4 Hypothyroidism is a disorder of endocrine system in which thyroid gland does not produce enough thyroid hormone due to destruction of thyroid gland. It is associated with many biochemical abnormalities including altered lipid levels which increase the cardiovascular risk. The earliest biochemical abnormality in hypothyroidism is an increase in serum thyroid stimulating hormone (TSH) associated with normal serum free T4 and T3 concentrations (subclinical hypothyroidism), followed by decrease in serum free T4 concentration, at which stage most patients have symptoms and benefit from treatment (overt hypothyroidism).⁵ It is well known that alterations in thyroid function result in changes in the composition and transport of lipoproteins.^6-8 Many studies have reported significant increase in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in hypothyroid patients.^9-11 Hence, hypothyroidism is known to influence lipid metabolism and is considered a significant cause of secondary dyslipidemia. Dyslipidemia is a well-known risk factor for cardiovascular diseases. Early diagnosis and management of hypothyroidism can significantly reduce the mortality and morbidity of dyslipidemic cardiovascular diseases.¹² Numerous studies have shown conflicting results concerning the degree of lipid changes in hypothyroidism and the effect of thyroxine substitution therapy.^13-16 The effect of thyroxine replacement on lipid levels are not completely understood and sufficient studies are currently lacking to substantiate this data with appropriate protocol. So, we have designed this study in our female patients clinically diagnosed with hypothyroidism to investigate lipid abnormalities when TSH <10 mIU/ml and >10 mIU/ml and additionally justify if screening of lipid profile needed with such altered TSH values in hypothyroid individual. Our second aim is to quantify the effect of lipid lowering drug and L-thyroxine therapy on TSH and serum lipid profiles.

METHODS

This prospective observational study was conducted in the out-patient ENT department of district hospital, KIMS, Koppal, Karnataka between January to June 2019. Forty female patients in the age group 35 to 55 yrs having one or more clinical manifestations of hypothyroidism (e.g. - fatigue, weakness, weight gain, hair loss, cold intolerance, muscle cramps, constipation, depression, irritability, memory loss, abnormal menstrual cycle) were selected, furthur divided into group A (n= 20, TSH between 5 and 10 mIU/ml) and group B (n=20, TSH > 10 mIU/ml) based on TSH values and categorised as cases. 20 euthyroid subjects in the same age range between 35 to 55 years were grouped as normal controls. Permission for the study was obtained from the College authorities prior to commencement. Written informed consent was taken for inclusion in the study.

Inclusion criteria

40 patients newly detected hypothyroid with dyslipidemia based on clinical history, biochemical blood serum analysis and Adult Treatment Panel (ATP) III National cholesterol Education Program (NCEP) guidelines and 20 eythroid normal controls

Exclusion criteria

Pregnant women, those with goitre, hyperthyroidism, diabetes, hypertension, coronary artery disease, renal and hepatic failure, obesity, patients exposed to thyroid hormone therapy or lipid lowering agent in the past 6 months, patients on statins, oral contraceptive pills and other medications that alter thyroid functions and lipid profile.

After an overnight fast, venous blood sample from each participant sent for lab and analysed for thyroid profile (TSH, fT3 and fT4) and lipid parameters (TC, LDL, high density lipoprotein (HDL), TG).

Lipid parameters obtained was then compared between the cases (n=40) and euthyroid controls (n=20). Lipid lowering drug was reserved for patients with dyslipidemia in group A and L-thyroxine therapy was initiated for patients in group B. These patients were then followed up after 3 months and with incremental doses of L-thyroxine (if needed) with repeat lipid profile and TSH. In the follow up period, effects of thyroxine substitution and lipid lowering drug on altered lipid profile and TSH was noted between both groups.

Upper limit of normal range of TSH was considered between 0.3 and 4.9 mIU/l. Patients with TSH level above 5 mIU/l was considered to be having hypothyroidism. Patients were considered to have dyslipidemia if the serum values for cholesterol greater than 200 mg%, LDL greater than 130 mg%, TG greater than 250 mg% and HDL less than 35 mg%.

Data analysis

Statistical analysis was done using paired t-test to evaluate the changes in lipid parameters before and after the initiation of L-thyroxine therapy and lipid lowering drug. Analysis of variance (ANOVA) test and Unpaired ‘t’ test were done to assess the significance between cases and controls. Pearson correlation coefficient test was done to evaluate the correlation of biochemical parameters with lipid lowering drug and L-thyroxine therapy. P values <0.05 were considered significant.

RESULTS

During January to June 2019, the patients were chosen among those attending the Outpatient Department (OPD) of ENT of KIMS, Koppal, Karnataka, India, and presenting with the clinical manifestations of hypothyroidism. A total of 60 patients, aged 35 to 55 years, were recruited for the study in which 40 cases were newly diagnosed with hypothyroidism with dyslipidemia (ATP III NCEP guidelines) and 20 euthyroid normal controls. Among these, all were female patients belonging to rural population. 40 cases were furthur classified into group A (TSH <10 mIU/ml) and group B (TSH>10 mIU/ml).

Mean total cholesterol (241.56±23.21), LDL cholesterol (151.96±29.60) and triglyceride level (212.28±21.73) in cases were higher than controls. HDL cholesterol was found significantly decreased in cases (49.59±11.69) Compared to controls (55.89±11.70) (Table 1).

Lipid lowering drug was started for group A (n=20; TSH< 10mIU/ml) as their lipid profile was altered and they had borderline TSH increase. None of the patients in this group had any symptom of hypothyroidism and so levothyroxine was not started for this grooup. We observed that there was significant reduction in the mean values of TSH from baseline (6.2±4.07) to (2.60±3.09) 3 month follow-up. Similarly, reduction was noted in the mean values of TC, LDL and TG from baseline to follow-up. However, a statistically significant increase in the mean values of HDL from baseline (35.5±6.73) to follow-up (46.45±4.64) was noted (Table 2).

SD: Standard deviation.

SD: Standard deviation.

Levothyroxine sodium is the hormone of choice for thyroid hormone replacement therapy. The daily replacement dose is usually 1.5 µg/kg (typically 100-150 µg). Based on weight of the patient, dose was titrated before initiation of therapy and given accordingly to patients. For group B (TSH>10 mIU/ml), 12 patients out of 20 had one or the other symptoms of hypothyroidism and also had altered lipid profile. Remaining 8 patients did not have symptoms of hypothyroidism though TSH was > 10mIU/ml but their lipid profile was deranged. So, we started for all 20 patients in group B, levothyroxine therapy by titrating the dose according to their weight. There was statistically significant reduction in the mean values of TSH from baseline (68.45±42.07) to 3 month (7.42±9.44) follow-up. Similarly, a statistically significant reduction in the mean values of TC from baseline (256±27.84) to 3 month (177.33±23.17) follow-up is depicted in Table 3. Moreover, a statistically significant reduction in the mean values of TG and LDL was observed from baseline to follow-up. But, in contrast to the above lipid parameters, HDL showed a statistically significant increase in the mean values from baseline (35.42±6.73) to (46.86±8.53) follow-up (Table 3).

DISCUSSION

Our study involved 60 female patients in the age group ranging from 35-55 years with mean age 42 years. Out of 60 female patients, 40 were cases and 20 were euthyroid controls. 40 cases were furthur divided into group A (TSH<10 mIU/ml) and group B (TSH>10 mIU/ml) based on TSH values.

In our study, mean total cholesterol, LDL cholesterol and triglycerides were found significantly increased whereas HDL cholesterol was found significantly decreased in cases compared to controls. Our findings were consistent with previous studies done by other investigators: Laway et al, Das et al, Saxena et al and Sharma et al.^17-20

Results of our study suggest the findings of dyslipidemia in hypothyroid patients. Correction of hypothyroidism rectifies the lipid abnormalities thereby decrease the cardiovascular complications.¹² Levothyroxine sodium is the hormone of choice for thyroid hormone replacement therapy. The daily replacement dose is usually 1.5 µg/kg (typically 100-150 µg).

We observed in our study a statistically significant reduction in the mean values of TC, TGs and LDL from baseline to 3 months follow-up following replacement therapy with lipid lowering drug in Group A (TSH<10 mIU/ml) and levothyroxine therapy in group B (TSH>10 mIU/ml). Various other authors (Monzani et al and Akbar et al) also reported significant reduction in the levels of lipid parameters following levothyroxine replacement therapy, thus supporting our observations.^21,22 Ineck et al and Meier et al did not observe any change in TG levels following levothyroxine replacement therapy contrary to our findings.^23,24 The response of HDL-C levels to thyroid substitution remains obscure. Few studies have shown an increase in HDL-C levels, whereas others showed either no change or decreases.^25,26 Our study also depicted a significant increase in mean HDL-C following replacement therapy with lipid lowering drug in group A and levothyroxine therapy in group B. Our finding regarding increase in HDL was supported by Asranna et al, who also observed a mild increase HDL from mean pretreatment levels of 41.14 to 43.43 mg/dl after replacement therapy with levothyroxine.²⁷ In contrast to our findings, Tanis et al reported that HDL-C levels decreased in few patients where TSH >10 mIU/ml.²⁸

CONCLUSION

The study has demonstrated and has furthur proved that hypothyroidism is an important cause of dyslipidemia. Therefore, patients diagnosed with hypothyroidism aged 35 years and above should be screened for dyslipidemia as it is one of the significant cardiovascular risk factor and if not treated at the appropriate time may give rise to life threatening cardiac complications much early in life. It was deduced from our study that, In hypothyroid patients with TSH <10 mIU/ml, Lipid lowering drug seemed to be sufficient to treat dyslipidemia and hence it can also be inferred that there is no role of L-thyroxine therapy in these patients except in symptomatic individuals, while in all hypothyroid patients with TSH >10 mIU/ml, it’s imperative to institute L-thyroxine therapy for restoration of TSH and altered lipids back to normal levels. However, as our sample size was small and duration of study was limited, other studies with larger sample size and of longer duration are required.

ACKNOWLEDGEMENTS

I would like to express my profound gratitude to all the participants.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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