|Year : 2014 | Volume
| Issue : 4 | Page : 266-270
Lipid profile in subclinical hypothyroidism: A biochemical study from tertiary care hospital
Mounika Guntaka1, Babulreddy Hanmayyagari2, Manne Rosaline3, V Nagesh4
1 Department of Biochemistry, Prime Hospital, Hyderabad, Andhra Pradesh, India
2 Department of Endocrinology, Employee's State Insurance Hospital, Hyderabad, Andhra Pradesh, India
3 Department of Biochemistry, Deccan College of Medical Sciences, Hyderabad, Andhra Pradesh, India
4 Department of Endocrinology, Care Hospital, Banjara Hills, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||16-Oct-2014|
Dr. Mounika Guntaka
Flat no-A 904, Sri Sai Ram Towers, Beside Alwyn Colony Water Tank, Hafeezpet, Hyderabad - 500 049, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Objective: To study lipid profile in patients of subclinical hypothyroidism and compare the same with matched controls. Materials and Methods: This single exposure observational study was conducted from June 2010 to March 2011 at our department of Biochemistry. Thirty patients with subclinical hypothyroidism were selected after careful exclusion; lipid profile was compared with matched controls. Statistical analysis was done with Student's t test. All values were expressed as mean ± SEM, where value of P ≤ 0.05 was considered statistically significant. Results: Between the two groups (group I - controls vs. group II - cases), the values were as follows: Mean serum total T 3 value was 115.03 ± 28.22 ng/dl vs. 107.13 ± 35.26 ng/dl (P = 0.3474); mean total T 4 was 7.0787 ± 1.6952 μg/dl vs. 6.8633 ± 1.3106 μg/dl (P = 0.532); mean TSH was 3.1730 ± 1.2772 μIU/ml vs. 9.7607 ± 4.1853 μIU/ml (P < 0.0001). Lipid profile pattern (group I vs. group II) was as follows: Mean total cholesterol (TC) 127.50 ± 7.18 mg/dl vs. 163.07 ± 41.32 mg/dl (P < 0.0001), mean triglycerides (TG) is 135.67 ± 13.84 mg/dl vs. 147.90 ± 66.27 mg/dl (P = 0.3231), low-density lipoprotein (LDL)-cholesterol is 61.17 ± 7.60 mg/dl vs. 99.83 ± 32.24 mg/dl (P < 0.0001), high-density lipoprotein (HDL)-cholesterol 39.13 ± 6.66 mg/dl vs. 35.27 ± 8.63 mg/dl (P = 0.0701), very low-density lipoprotein (VLDL) levels are 33.533 ± 14.375 mg/dl vs. 31.077 ± 14.202 mg/dl (P = 0.5235). Conclusion: Subclinical hypothyroidism is associated with increased serum total cholesterol and LDL-Cholesterol levels. Therefore, there is a potential association between Subclinical hypothyroidism and atherosclerosis.
Keywords: Cardiovascular risk, lipid profile, subclinical hypothyroidism, thyroid stimulating hormone
|How to cite this article:|
Guntaka M, Hanmayyagari B, Rosaline M, Nagesh V. Lipid profile in subclinical hypothyroidism: A biochemical study from tertiary care hospital. CHRISMED J Health Res 2014;1:266-70
|How to cite this URL:|
Guntaka M, Hanmayyagari B, Rosaline M, Nagesh V. Lipid profile in subclinical hypothyroidism: A biochemical study from tertiary care hospital. CHRISMED J Health Res [serial online] 2014 [cited 2021 Apr 11];1:266-70. Available from: https://www.cjhr.org/text.asp?2014/1/4/266/143014
| Introduction|| |
Subclinical hypothyroidism (mild hypothyroidism or biochemical hypothyroidism) is defined as normal serum Total T 4 (TT 4 )/free T 4 (FT 4 ) and Total T 3 (TT 3 )/free T 3 (FT 3 ) levels in the presence of elevated serum thyroid stimulating hormone (TSH) levels. ,, The prevalence of this condition in adults is 4-10%. It is higher in women than in men and increases with age, reaching a peak of 21% in women and 16% in men over 74 years of age. , The etiology and nature of SCH are the same as in overt hypothyroidism.
The symptoms pertaining to SCH are nonspecific and depend on individual sensitivity to circulating hormones or tissue level of hormones. 
Though SCH can affect various organ systems, the cardiovascular system is the major target. In SCH patients, the cardiac hemodynamic changes reported are increased systemic vascular resistance (SVR), diastolic dysfunction, and reduced systolic function that are similar to those observed in overt hypothyroidism.  SCH could impair vascular function by inducing an increase in SVR and arterial stiffness and by altering endothelial function and thereby potentially increasing the risk of atherosclerosis and coronary artery disease. , Moreover, an inconsistent change to atherogenic lipids may also add to the cardiovascular risks. 
The epidemiological data about cardiovascular risk in SCH is controversial, as some of the studies have shown an increase in myocardial infarction  and heart failure,  whereas others did not find any increase in cardiovascular disease or mortality.  This discrepancy could be due to differences in study population (viz. age, sex), TSH range that defines SCH, methods of evaluation of cardiovascular disease, and differences in adjustments for known risk factors for cardiovascular disease.
As SCH is being diagnosed more frequently in young and middle-aged people, there is a need to know the effect of SCH on cardiovascular risk factors in young South Indians. Therefore, the objective of this study is to analyze the relation between SCH and serum lipid parameters in this subgroup.
| Materials and Methods|| |
This single exposure observational study was conducted from June 2010 to March 2011 at our Department of Biochemistry, in subjects diagnosed with SCH [defined as normal TT 3 /FT 3 , normal TT 4 /FT 4 , and with increased TSH]. As our hospital does not have an Endocrinology department, we pooled treatment naive SCH patients to the Endocrinology departments of other hospitals after obtaining informed consent.
Patients with history of diabetes mellitus, coronary heart disease, pregnancy, obesity, post-menopausal status, acute illness, and other disorders that affect lipid metabolism were excluded. Patients who were exposed to thyroid hormone therapy or lipid-lowering agent in the past 6 months were also excluded.
Thirty patients (27 females and 3 males) were included in the present study and thirty age- and sex-matched and regularly menstruating healthy controls, who were evaluated for Thyroid Function test were randomly recruited from staff and volunteers. Informed consent was obtained from both cases and controls; this study was approved by the ethical committee.
Blood samples were drawn at 08:00 h after an overnight fast in a sterile bottle. Serum was separated for the estimation of serum TSH, TT 3 , TT 4 , and total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), which were derived from TC and TG, using Friedwald's Formula [LDL = TC - (HDL + TG/5)], , Very low-density lipoprotein (VLDL) derived from TG.
T 3 , T 4 , and TSH were estimated by using quantitative solid phase enzyme-linked immune sorbent assay (ELISA), whereas TC was estimated with photometric determination according to the CHOD PAP method; TG and HDL were estimated by using the enzymatic colorimetric method.
Normal reference values are as follows: TT 3 : 60-200 ng/dl, TT 4 : 5-12 μg/dl, TSH: 0.3-5.5 μIU/ml, Total cholesterol: 100-200 mg/dl, TG: 150-199 mg/dl, LDL: 100-130 mg/dl, VLDL: 6-35 mg/dl, HDL: 40-60 mg/dl.
Statistical analysis was done with the Student t test, where all values were expressed as mean ± SEM, and value of P ≤ 0.05 was considered statistically significant.
| Results|| |
As SCH is defined as elevated levels of TSH with respect to normal levels of T 3 and T 4 ; hence, T 3 and T 4 levels were matched with a group I (controls) and group II (cases).
In group I individuals, the mean serum T 3 level was 115.03 ± 28.22 ng/dl. In group II individuals, the mean serum T 3 level is 107.13 ± 35.26 ng/dl (P = 0.3474).
In group I individuals, the mean serum T 4 level is 7.0787 ± 1.6952 μg/dl. In group II individuals, the mean serum T 4 level is 6.8633 ± 1.3106 μg/dl (P = 0.5352).
The levels of TSH are significantly higher in group II (9.7607 ± 4.1853 μIU/ml) compared to group I (3.1730 ± 1.2772 μIU/ml), P < 0.0001, which is considered to be statistically significant.
There is a significant increase in the serum TC level in group II individuals (163.07 ± 41.32 mg/dl) when compared to group I (127.50 ± 7.18 mg/dl), P < 0.0001; this difference is considered to be statistically significant.
There is also a significant increase in serum LDL-Cholesterol in group II individuals (99.83 ± 32.24 mg/dl) when compared to group I individuals (61.17 ± 7.60), P < 0.0001, which is statistically significant.
There is no significant difference in serum HDL-Cholesterol among the group I (39.13 ± 6.66 mg/dl) and group II (35.27 ± 8.63 mg/dl), P = 0.0701, which is not quite statistically significant.
In group I individuals, the mean serum TG is 135.67 ± 13.84 mg/dl. In group II individuals, the levels are 147.90 ± 66.27, P = 0.3231, which is not statistically significant. A small increase in serum TG level in group II compared to group I may be noted [Table 1] and [Figure 1].
There is no significant difference in serum VLDL levels among the group I (33.533 ± 14.375) and group II (31.077 ± 14.202) P = 0.5235, which is statistically insignificant.
| Discussion|| |
The present study was conducted among the subclinical hypothyroid patients attending various tertiary care hospitals. The possible correlation between SCH and serum concentrations of lipids was evaluated.
The pathophysiology of dyslipidemia in hypothyroidism is not exactly known. However, the proposed mechanisms for dyslipidemia in hypothyroidism are as follows:
- Primary accumulation of LDL cholesterol due to reduction in the number of cell surface receptors for LDL results in decreased catabolism of LDL 
- Diminished secretion of cholesterol into bile has been demonstrated in hypothyroid rats 
- Reduced cholesteryl ester transfer (the net transfer of cholesterol from HDL to LDL and VLDL) in hypothyroidism may minimize the increase in serum LDL cholesterol concentrations 
- Reduced lipoprotein lipase activity is responsible for the development of hypertriglyceridemia in hypothyroidism although the rate of TG synthesis is normal. 
The relationship between subclinical hypothyroidism and serum lipids remains controversial.  In several cross-sectional studies, subclinical hypothyroidism was found to be associated with a variable and somewhat inconsistent increase in TC and in LDL-C, ,, higher plasma oxidized LDL-C levels,  and inconsistent changes in serum levels of HDL-C.  As expected, the lipid pattern is more abnormal in individuals with serum TSH greater than 10 mIU/liter,  and it is more deranged in those who smoke. 
In our study, TC and LDL-C were significantly increased and non-significantly elevated serum TG levels were seen in group II subjects when compared to group I. There was no significant difference in the levels of HDL-C and VLDL-C in two groups. These results correlated well with the Colorado thyroid disease prevalence study, which showed that TC and LDL-C in SCH were significantly higher than that in euthyroidism but TG and HDL-C were not significantly different.  Whereas the results are consistent with few of the available Indian studies in terms of LDL, TC levels and not with TG and VLDL levels. , These differences could be a result of our small sample size, difference in age, ethnicity, and dietary habits of selected samples.
The sample size of this study was small. We did not carry out anti-TPO antibody or serum lipoprotein (a) test in our patients. T 3 , T 4 , and TSH were estimated using ELISA as new generation assay was not available at our centre, and we did not observed the effect of thyroxine therapy on this lipid profile.
| Conclusion|| |
Subclinical hypothyroidism is associated with increased serum TC and LDL-C levels. Therefore, there is a potential association between subclinical hypothyroidism and atherosclerosis. Larger studies are needed to prove this association in Indian patients.
| References|| |
Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 2003;88:2438-44.
Singh K, Singh S. Alterations in lipid fraction levels in subclinical hypothyroidism in north Indian population. Indian J Fundam Appl Life Sci 2011;1:127-32.
Verma A, Harikumar KV, Muthukrishnan J, Modi KD. Obesity and subclinical hypothyroidism. Saudi Med J 2008;29:1135-8.
Surks MI, Ocampo E. Subclinical thyroid disease. Am J Med 1996;100:217-23.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.
Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76-131.
Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: Response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002;87:1533-8.
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam study. Ann Intern Med 2000;132:270-8.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al.
The spectrum of thyroid disease in a community: The Whickham survey. Clin Endocrinol (Oxf) 1977;7:481-93.
Ladenson PW, Wilson MC, Gardin J, Kronmal R, Kuller L, Tracy R, et al.
Relationship of subclinical hypothyroidism to cardiovascular risk factors and disease in an elderly population. Thyroid 1994;4:S-18.
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001;344:501-9.
Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, et al.
Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol 2008;52:1152-9.
Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al
. The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55-68.
Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB. Defects of receptor mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo
. Proc Natl Acad Sci U S A 1981;78:2591-5.
Gebhard RL, Prigge WF. Thyroid hormone differentially augments biliary sterol secretion in the rat. II. The chronic bile fistula model. J Lipid Res 1992;33:1467-73.
Ritter MC, Kannan CR, Bagdade JD. The effects of hypothyroidism and replacement therapy on cholesteryl ester transfer. J Clin Endocrinol Metab 1996;81:797-800.
Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB. Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo.
Proc Natl Acad Sci U S A 1981;78:2591-5.
Duntas LH. Thyroid disease and lipids. Thyroid 2002;12:287-93.
Lindeman RD, Schade DS, LaRue A, Romero LJ, Liang HC, Baumgartner RN, et al
. Subclinical hypothyroidism in a biethnic, urban community. J Am Geriatr Soc 1999;47:703-9.
Bauer DC, Ettinger B, Browner WS. Thyroid function and serum lipids in older women: A population-based study. Am J Med 1998;104:546-51.
Duntas LH, Mantzou E, Koutras DA. Circulating levels of oxidized low-density lipoprotein in overt and mild hypothyroidism. Thyroid 2002;12:1003-7.
Pirich C, Mullner M, Sinzinger H. Prevalence and relevance of thyroid dysfunction in 1922 cholesterol screening participants. J Clin Epidemiol 2000;53:623-9.
Miura S, Iitaka M, Yoshimura H, Kitahama S, Fukasawa N, Kawakami Y, et al.
Disturbed lipid metabolism in patients with subclinical hypothyroidism: Effect of L-thyroxine therapy. Intern Med 1994;33:413-7.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.
Bandyopadhyay SK, Basu AK, Pal SK, Roy P, Chakrabarti S, Pathak HS, et al.
A study on dyslipidaemia in subclinical hypothyroidism. J Indian Med Assoc 2006;104:622-4, 626.
Asranna A, Taneja RS, Kulshreshta B. Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile. Indian J Endocrinol Metab 2012;16:347-9.