Background: Subclinical hypothyroidism (SCH) is defined as high TSH and normal thyroxine. Data on the effects of early substitution by levothyroxine on psychophysical health in SCH are still not consistent enough to support its introduction.
Methods: Clinical parameters, biochemical data and quality of life (Short Form 36 questionnaire) were measured before the intervention and 3 months after the euthyroid state had been achieved in SCH patients.
Results: Significant reduction in body weight (p=0.030), systolic and diastolic blood pressure (p=0.024, p=0.019), homocysteine (p<0.001), leukocytes and neutrophils (p=0.011, p=0.001), INR (p=0.049), K levels (p=0.040, p=0.013), HbA1c (p=0.001), fasting insulin (p<0.001) and insulin resistance measured by HOMA index (p<0.001), lipid parameters (total cholesterol (p<0.001), LDL-cholesterol (p<0.001), triglycerides (p=0.007), apoB (p=0.022), Lp(a) (p<0.001), LDL/HDL (p=0.008), LAP (p=0.04) and apoB/apoA1 ratios (p<0.023)), TSH (p<0.001) and tAbs (p<0.001) was recorded. Frequency of fatty liver (20% to 2.9%, p=0.016), hyperlipidemia (85% to 65.7%, p=0.001) and metabolic syndrome (34.3% to 2.9%, p=0.070) significantly decreased. A statistically significant positive association was found between the average dose of levothyroxine and changes in physical functioning (r=0.391, p=0.020), vitality (r=0.393, p=0.020), mental health (r=0.374, p=0.027) and overall dimensions of mental health (r=0.376, p=0.026). With increasing doses of levothyroxine, the previously listed scores of SF 36 grew (r=0.296, p=0.084).
Conclusions: Early substitution of SCH improved the many clinical and biochemical parameters related to cardiovascular risk. Quality of life was also improved, and correlated only with thyroxine doses suggesting an indirect relationship between the degree of hypothyroidism and quality of life.
1. Hennessey JV, Espaillat R. Subclinical hypothyroidism: a historical view and shifting prevalence. Int J Clin Pract 2015; 69(7): 771-82.
2. Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J 2013; 2(4): 215-28.
3. Pesic MM, Radojkovic D, Antic S, Kocic R, Stankovic- Djordjevic D. Subclinical hypothyroidism: association with cardiovascular risk factors and components of metabolic syndrome. Biotechnol Biotechnol Equip 2015; 29(1): 157-63.
4. Pyati A, Dhuttargi S, Das D. Assessment of the Cardiovascular Risk in Subclinical Hypothyroidism. Int J Pharm Biol Sci 2012; 2230-7605.
5. Karmisholt J, Andersen S, Laurberg P. Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy. Eur J Endocrinol 2011; 164(3): 317-23.
6. Li M, Tang Z. Subclinical hypothyroidism: to treat or not to treat? Med Princ Pract. Karger Publishers 2015; 24(1): 99-100.
7. Zhao M, Tang X, Yang T, Zhang B, Guan Q, Shao S, et al. Lipotoxicity, a Potential Risk Factor for the Increasing Prevalence of Subclinical Hypothyroidism? J Clin Endocrinol Metab 2015; 100(5): 1887-94.
8. Andersen MN, Olsen A-MS, Madsen JC, Faber J, Torp- Pe dersen C, Gislason GH, et al. Levothyroxine Substitution in Patients with Subclinical Hypothyroidism and the Risk of Myocardial Infarction and Mortality. Eugenin EA, editor. PLoS One. Public Library of Science 2015; 10(6): e0129793.
9. Walsh JP, Ward LC, Burke V, Bhagat CI, Shiels L, Henley D, et al. Small Changes in Thyroxine Dosage Do Not Pro duce Measurable Changes in Hypothyroid Symptoms, Well-Being, or Quality of Life: Results of a Double- Blind, Randomized Clinical Trial. J Clin Endocrinol Metab 2006; 91(7): 2624-30.
10. Carr D, McLeod DT, Parry G, Thornes HM. Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment. Clin Endocrinol (Oxf) 1988; 28(3): 325-33.
11. Nyström E, Caidahl K, Fager G, Wikkelsö C, Lundberg PA, Lindstedt G. A double-blind cross-over 12-month study of l-thyroxine treatment of women with ≫subclinical ≪ hypothyroidism. Clin Endocrinol (Oxf). Blackwell Publishing Ltd; 1988; 29(1): 63-76.
12. Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC. L-Thyroxine therapy in subclinical hypothyroidism. A double- blind, placebo-controlled trial. Ann Intern Med 1984; 101(1): 18-24.
13. Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, et al. Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment. Clin Investig 1993; 71(5): 367-71.
14. Kaur V, Singh K, Verma M. Changes in biochemical markers of renal function in subclinical and overt hypo - thyroidism. Int J Bioassays 2015; 4(4): 3799-802.
15. Gullu S, Sav H, Kamel N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism. Eur J Endocrinol 2005; 152(3): 355-61.
16. Kahn HS. The Lipid Accumulation Product Is Better Than BMI for Identifying Diabetes. Diabetes Care 2005; 29(1).
17. Lakka H-M, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288(21): 2709-16.
18. Wallace TM, Matthews DR. The assessment of insulin resistance in man. Diabet Med 2002; 19(7): 527-34.
19. Pekmezovic T, Kisic Tepavcevic D, Kostic J, Drulovic J. Validation and cross-cultural adaptation of the diseasespecific questionnaire MSQOL-54 in Serbian multiple sclerosis patients sample. Qual Life Res 2007; 16(8): 1383-7.
20. Basta I, Pekmezović T, Padua L, Stojanović V, Stević Z, Nikolić A, et al. Validation of Serbian version of the disease- specific myasthenia gravis questionnaire. Acta Neurol Scand 2010; 122(2): 110-4.
21. Bose A, Sharma N, Hemvani N, Chitnis DS. A Hospital Based Prevalence Study on Thyroid Disorders in Malwa region of Central India. Int J Curr Microbiol App Sci 2015; 4(6): 604-11.
22. Cerit ET, Akturk M, Altinova AE, Tavil Y, Ozkan C, Yayla C, et al. Evaluation of body composition changes, epicardial adipose tissue, and serum omentin-1 levels in overt hypothyroidism. Endocrine 2015; 49(1): 196-203.
23. Erdogan M, Canataroglu A, Ganidagli S, Kulaksizoglu M. Metabolic syndrome prevalence in subclinic and overt hypothyroid patients and the relation among metabolic syndrome parameters. J Endocrinol Invest. Springer International Publishing; 34(7): 488-92.
24. Kottagi SS, Rathi DB, Dongre NN. Evaluation of LDLCholesterol / HDL-Cholesterol Ratio as Predictor of Dyslipidemia in Subclinical Hypothyroidism. Journal of Krishna Institute of Medical Sciences University 2014; 3(1): 34-40.
25. Marchiori RC, Pereira LAF, Naujorks AA, Rovaris DL, Meinerz DF, Duarte MMMF, et al. Improvement of blood inflammatory marker levels in patients with hypothyroidism under levothyroxine treatment. BMC Endocr Disord 2015; 15(1): 32.
26. Aksoy DY, Cinar N, Harmanci A, Karakaya J, Yildiz BO, Usman A, et al. Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy. Med Sci Monit. International Scientific Literature, Inc.; 2013; 19: 210-5.
27. Monzani F, Caraccio N, Kozàkowà M, Dardano A, Vittone F, Virdis A, et al. Effect of Levothyroxine Replacement on Lipid Profile and Intima-Media Thickness in Subclinical Hypothyroidism: A Double- Blind, Placebo-Controlled Study. J Clin Endocrinol Metab 2004; 89(5): 2099-106.
28. Gunduz M, Gunduz E, Kircelli F, Okur N, Ozkaya M. Role of surrogate markers of atherosclerosis in clinical and subclinical thyroidism. Int J Endocrinol. Hindawi Pu - blishing Corporation 2012; 2012: 109797.
29. Yadav A, Arora S, Saini V, Arora MK, Singh R, Bhattacharjee J. Influence of thyroid hormones on biochemical parameters of liver function: a case-control study in North Indian population. Internet J Med Updat 2013; 8(1): 4-8.
30. Christ-Crain M, Meier C, Huber P, Zulewski H, Staub J-J, Müller B. Effect of restoration of euthyroidism on peripheral blood cells and erythropoietin in women with subclinical hypothyroidism. Hormones (Athens) 2(4): 237-42.
31. Chadarevian R, Bruckert E, Giral P, Turpin G. Relationship between thyroid hormones and fibrinogen levels. Blood Coagul Fibrinolysis 1999; 10(8): 481-6.
32. Chadarevian R, Bruckert E, Leenhardt L, Giral P, Ankri A, Turpin G. Components of the Fibrinolytic System Are Differently Altered in Moderate and Severe Hypo thyroidism. J Clin Endocrinol Metab 2001; 86(2): 732-7.
33. Cantürk Z, Çetinarslan B, Tarkun I, Canturk NZ, Özden M, Duman C. Hemostatic System as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism. Thyroid 2003; 13(10): 971-7.
34. Lioudaki E, Mavroeidi NG, Mikhailidis DP, Ganotakis ES. Subclinical hypothyroidism and vascular risk: an update. Hormones (Athens) 12(4): 495-506.
35. Al Sayed A, Al Ali N, Bo Abbas Y, Alfadhli E. Subclinical hypothyroidism is associated with early insulin resistance in Kuwaiti women. Endocr J 2006; 53(5): 653-7.
36. Dessein PH, Joffe BI, Stanwix AE. Subclinical Hypo - thyroidism is Associated with Insulin Resistance in Rheuma toid Arthritis. Thyroid. Mary Ann Liebert, Inc.; 2004; 14(6): 443-6.
37. Tuzcu A, Bahceci M, Gokalp D, Tuzun Y, Gunes K. Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia. Endocr J 2005; 52(1): 89-94.
38. Wang C-Y, Chang T-C, Chen M-F. Associations between subclinical thyroid disease and metabolic syndrome. Endocr J 2012; 59(10): 911-7.
39. Anagnostis P, Efstathiadou ZA, Slavakis A, Selalmatzidou D, Poulasouchidou M, Katergari S, et al. The effect of Lthyroxine substitution on lipid profile, glucose homeostasis, inflammation and coagulation in patients with subclinical hypothyroidism. Int J Clin Pract 2014; 68(7): 857-63.
40. Garduno-Garcia J d. J, Alvirde-Garcia U, Lopez-Carrasco G, Padilla Mendoza ME, Mehta R, Arellano-Campos O, et al. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol 2010; 163(2): 273-8.
41. Priyanka G. Rakshasmare PNJ. Apolipoprotein b / apo - lipo protein a1 ratio: an improved marker of cardiovascular risk in hypothyroidism. Int J Curr Res Rev 2014; 6(10): 86-9.
42. Cheserak MJ, Wu GR, Ntazinda A, Shi YH, Shen LY, Le GW. Association between thyroid hormones, lipids and oxidative stress markers in subclinical hypothyroidism. J Med Biochem 2015; 35: 323-31.
43. Tsimihodimos V, Bairaktari E, Tzallas C, Miltiadus G, Liberopoulos E. The Incidence of Thyroid Function Abnormalities in Patients Attending an Outpatient Lipid Clinic. Thyroid 1999; 9(4): 365-8.
44. Tzotzas T, Krassas GE, Konstantinidis T, Bougoulia M. Changes in Lipoprotein(a) Levels in Overt and Subclinical Hypothyroidism Before and During Treatment. Thyroid 2000; 10(9): 803-8.
45. Waring AC, Rodondi N, Harrison S, Kanaya AM, Simo n - sick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study. Clin Endocrinol (Oxf). NIH Public Access 2012; 76(6): 911-8.
46. Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, et al. A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol (Oxf) 2010; 72(5): 696-701.
47. Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M, et al. Health-related quality of life in patients with thyroid disorders. Qual Life Res 2004; 13(1): 45-54.
48. Harris B, Othman S, Davies JA, Weppner GJ, Richards CJ, Newcombe RG, et al. Association between postpartum thyroid dysfunction and thyroid antibodies and depression. BMJ. BMJ Group 1992; 305(6846): 152-6.
49. Park YJ, Lee EJ, Lee YJ, Choi SH, Park JH, Lee SB, et al. Subclinical hypothyroidism (SCH) is not associated with metabolic derangement, cognitive impairment, depression or poor quality of life (QoL) in elderly subjects. Arch Gerontol Geriatr 50: e68-73.
50. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt- Rasmussen U, Henry J-F, et al. Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Thyroid 2003; 13(1): 3-3.