Abstract
The implications of subclinical hypothyroidism (SCH) are many amongst which the most important is progression to overt hypothyroidism. Other debatable aspects are its association with cardiovascular risk, neuromuscular and psychiatric dysfunction, increased predisposition to developing metabolic syndrome and an underlying pro-inflammatory state. We aimed to study the lipid profile, lipoprotein(a) [Lp(a)] and hsCRP levels and insulin resistance in a group of patients with SCH in a referral hospital and see if any significant differences exist between them and euthyroids. This is a case–control study where the selection of controls and cases was based on the thyroid profile. Subjects were selected on their visit to clinical biochemistry lab for thyroid function tests. 33 euthyroids were taken as controls (Group I) and 38 patients comprising of subclinical hypothyroids were grouped as cases (Group II). Serum thyroid stimulating hormone (TSH) was in the range of 0.5–5.0 mIU/L for euthyroids and for subclinical hypothyroids the concentration of TSH was more than 5 mIU/L. The concentration of tri-iodothyronine (T3) and thyroxine (T4) were in normal reference range in both the groups. Individual lipid profile parameters failed to show a significant p value between cases and controls. The LDL/HDL ratio was highly significant (p value < 0.0001) and hsCRP was also statistically between the two groups (p value = 0.0054). Lp(a) and insulin resistance did not differ significantly. SCH is a common disorder that frequently progresses to overt hypothyroidism. This study underlines the importance of LDL/HDL ratio rather than measurement of individual lipid profile parameters in bringing to light the dyslipidemic state associated with SCH. Moreover the use of hsCRP to detect an underlying pro-inflammatory state in SCH can also be emphasized.
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References
Biondi B, Cooper DS. The clinical significance of thyroid dysfunction. Endocr Rev. 2008;29(1):76–131.
Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65–71.
Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55–68.
Díez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89(10):4890–7.
Elder J, McClelland A, O’Reilly DS, Packard CJ, Series JJ, Shepherd J. The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. Ann Clin Biochem. 1990;27:110–3.
Staub J-J, Althaus BU, Engler H, et al. Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med. 1992;92:631.
Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. J Am Med Assoc. 2006;295(9):1033–41.
Rodondi N, Aujesky D, Vittinghoff E, Cornuz J, Bauer DC. Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Am J Med. 2006;119(7):541–51.
Ochs N, Auer R, Bauer D, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148(11):832–45.
Hueston WJ, King DE, Geesey ME. Serum biomarkers for cardiovascular inflammation in subclinical hypothyroidism. Clin Endocrinol. 2005;63(5):582–7.
Duntas LH, Wartofsky L. Cardiovascular risk and subclinical hypothyroidism: focus on lipids and new emerging risk factors: what is the evidence? Thyroid. 2007;17(11):1075–84.
Allan WC, Haddow JE, Palomaki GE, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen. 2000;7:127–30.
Leung AS, Miller LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993;81:349–53.
Lincoln SR, Ke RW, Kutteh WH. Screening for hypothyroidism in infertile women. J Reprod Med. 1999;44:455–7.
Baldini IM, Vita A, Mauri MC, et al. Psychopathological and cognitive features in subclinical hypothyroidism. Prog Neuropsychopharmacol Biol Psychiatry. 1997;21:925–35.
Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92(5):1715–23.
Lopez-Majano V, Abraira C. Laboratory diagnosis in thyroid disease. Ill Med J. 1981;159(2):95–101.
Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481–93.
Cooper DS. Subclinical hypothyroidism. N Engl J Med. 2001;345(4):260–5.
Ayala A, Danese MD, Ladenson PW. When to treat mild hypothyroidism. Endocrinol Metab Clin N Am. 2000;29:399–415.
Bhaskaran S, Kumar H, Nair V, et al. Subclinical hypothyroidism: indications for thyroxine therapy. Thyr Res Pract. 2004;1(3):10–4.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1995;7:481–93.
Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489–99.
Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, Braverman LE. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab. 2002;87:3221–6.
Diez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89:4890–7.
Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. J Am Med Assoc. 2004;292:2591–9.
Michalopoulou G, Alevizaki M, Piperingos G, Mitsibounas D, Mantzos E, Adamopoulos P, Koutras DA. High serum cholesterol levels in persons with’ high-normal’ TSH levels: should one extend the definition of subclinical hypothyroidism? Eur J Endocrinol. 1998;138:141–5.
Iqbal A, Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromso Study. J Intern Med. 2006;260:53–61.
Asvold BO, Vatten LJ, Nilsen TI, Bjøro T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur J Endocrinol. 2007;156(2):181–6.
Bakker SJ, ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab. 2001;86:1206–11.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. Lipid profiles and cardiovascular disease in the Whickham area with particular reference to thyroid failure. Clin Endocrinol. 1977;7:495–508.
Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med. 2004;2:351–5.
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.
Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, Usa T, Ashizawa K, Yokoyama N, Maeda R, Nagataki S, Eguchi K, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab. 2004;89:3365–70.
Lindeman RD, Schade DS, LaRue A, Romero LJ, Liang HC, Baumgartner RN, Koehler KM, Garry PJ. Subclinical hypothyroidism in a biethnic, urban community. J Am Geriatr Soc. 1999;47:703–9.
Bindels AJ, Westendorp RG, Frolich M, Seidell JC, Blokstra A, Smelt AH. The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding? Clin Endocrinol. 1999;50:217–20.
Duntas LH. Thyroid disease and lipids. Thyroid. 2002;12:287–93.
Santi A, Duarte MM, Moresco RN, et al. Association between thyroid disease, lipids, oxidative stress biomarkers in overt hypothyroidism. Clin Chem Lab Med. 2010;48(11):1635–9.
Fatourechi V. Subclinical hypothyroidism: when to treat, when to watch? Consultant. 2004;44(4):533–9.
Richmond W. When and how to measure lipids and their role in CHD risk prediction. Br J Diabetes Vasc Dis. 2003;3:191–8.
Fernandez M, Webb D. The LDL to HDL cholesterol ratio as a valuable tool to evaluate coronary heart disease risk. J Am Coll Nutr. 2008;27(1):1–5.
Tian L, Fu M. The relationship between high density lipoprotein subclass profile and plasma lipids concentrations. Lipids Health Dis. 2010;9:118.
Kung AW, Pang RW, Janus ED. Elevated serum lipoprotein(a) in subclinical hypothyroidism. Clin Endocrinol. 1995;43:445–9.
Tsimihodimos V, Bairaktari E, Tzallas C, Miltiadus G, Liberopoulos E, Elisaf M. The incidence of thyroid function abnormalities in patients attending an outpatient lipid clinic. Thyroid. 1999;9:365–8.
Caraccio N, Ferranini 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.
Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol (Oxf). 2004;61:232–8.
Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, Muller B. Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial. Atherosclerosis. 2003;166:379.
Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K. Subclinical hypothyroidism may be associated with elevated high-sensitive creactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J. 2005;52(1):89–94.
Singh S, Singh K. Alterations in lipid fraction levels in subclinical hypothyroidism in north Indian population. Indian J Fundam Appl Life Sci. 2011;1(2):127–32.
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Mahto, M., Chakraborthy, B., Gowda, S.H. et al. Are hsCRP Levels and LDL/HDL Ratio Better and Early Markers to Unmask Onset of Dyslipidemia and Inflammation in Asymptomatic Subclinical Hypothyroidism?. Ind J Clin Biochem 27, 284–289 (2012). https://doi.org/10.1007/s12291-012-0206-y
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DOI: https://doi.org/10.1007/s12291-012-0206-y