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Current Drug Safety

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ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

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Clinical Trial

The Effect of Levothyroxine in Comparison with Placebo on Serum Osteocalcin Levels in Patients with Subclinical Hypothyroidism

Author(s): Reihaneh Rezaee, Masoud Mohebbi*, Mozhgan Afkhamizadeh, Mohammad Ali Yaghoubi, Mansoureh Hoseinzadeh, Mona Najaf Najafi and Amirhossein Sahebkar*

Volume 17, Issue 1, 2022

Published on: 11 August, 2021

Page: [64 - 69] Pages: 6

DOI: 10.2174/1574886316666210525102230

Price: $65

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Abstract

Background and Objective: Subclinical hypothyroidism can potentially develop into overt hypothyroidism. Thyroid hormones have substantial roles in metabolism and glucose homeostasis and thus, are closely related to determinant factors of metabolic syndromes, such as obesity and insulin resistance. Osteocalcin is considered a predictor of metabolic conditions in thyroid diseases. This study aimed to investigate the effect of levothyroxine vs. placebo on serum osteocalcin levels in patients with subclinical hypothyroidism.

Methods: This randomized clinical trial was performed on 30 patients with subclinical hypothyroidism, who were referred to the endocrine clinics of Ghaem and Imam Reza hospitals in Mashhad, Iran. After giving informed consent, patients were randomly divided into intervention (50 μg/- day levothyroxine for 2 months) and control (placebo) groups. Serum levels of osteocalcin, thyroid hormones, lipid profile, insulin, and fasting glucose, as well as other clinical and anthropometric data, were measured at baseline and at the end of the study. SPSS was used to analyze the data, and p < 0.05 was considered significant.

Results: Mean age in the intervention and control groups was 35.07 ± 9.94 and 31.30 ± 4.30, respectively (p = 0.20). There was no significant difference between osteocalcin levels before and after the intervention in either of the groups (p = 0.54). TSH level was significantly decreased in the levothyroxine group after the intervention (p < 0.01). T4 level was significantly increased in the intervention group (p = 0.02).

Conclusion: Levothyroxine had no significant effect on the increasing levels of serum osteocalcin in patients with subclinical hypothyroidism.

Keywords: Subclinical hypothyroidism, metabolic syndrome, insulin resistance, levothyroxine, osteocalcin, TSH.

« Previous Next »
[1]
Peeters RP. Subclinical hypothyroidism. N Engl J Med 2017; 376(26): 2556-65.
[http://dx.doi.org/10.1056/NEJMcp1611144] [PMID: 28657873]
[2]
Baumgartner C, Blum MR, Rodondi N. Subclinical hypothyroidism: Summary of evidence in 2014. Swiss Med Wkly 2014; 144: w14058.
[http://dx.doi.org/10.4414/smw.2014.14058] [PMID: 25536449]
[3]
Gao C, Wang Y, Li T, Huang J, Tian L. Effect of subclinical Hpothyroidism on the skeletal system and improvement with short-term thyroxine therapy. Oncotarget 2017; 8(52): 90444-51.
[http://dx.doi.org/10.18632/oncotarget.19568] [PMID: 29163843]
[4]
Blum MR, Bauer DC, Collet TH, et al. Thyroid Studies Collaboration. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 2015; 313(20): 2055-65.
[http://dx.doi.org/10.1001/jama.2015.5161] [PMID: 26010634]
[5]
Rodondi N, Newman AB, Vittinghoff E, et al. Subclinical Hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005; 165(21): 2460-6.
[http://dx.doi.org/10.1001/archinte.165.21.2460] [PMID: 16314541]
[6]
Parle J, Roberts L, Wilson S, et al. A randomized controlled trial of the effect of Thyroxine replacement on cognitive function in community-living elderly subjects with subclinical Hypothyroidism: The Birmingham Elderly Thyroid study. J Clin Endocrinol Metab 2010; 95(8): 3623-32.
[http://dx.doi.org/10.1210/jc.2009-2571] [PMID: 20501682]
[7]
Aronow MA, Gerstenfeld LC, Owen TA, Tassinari MS, Stein GS, Lian JB. Factors that promote progressive development of the Osteoblast Phenotype in cultured fetal rat Calvaria cells. J Cell Physiol 1990; 143(2): 213-21.
[http://dx.doi.org/10.1002/jcp.1041430203] [PMID: 2332447]
[8]
Yoneda M, Takatsuki K, Yamauchi K, et al. Influence of Thyroid function on serum bone Gla protein. Endocrinol Jpn 1988; 35(1): 121-9.
[http://dx.doi.org/10.1507/endocrj1954.35.121] [PMID: 3260858]
[9]
Kojima N, Sakata S, Nakamura S, et al. Serum concentrations of Osteocalcin in patients with Hyperthyroidism, Hypothyroidism and subacute Thyroiditis. J Endocrinol Invest 1992; 15(7): 491-6.
[http://dx.doi.org/10.1007/BF03348786] [PMID: 1447487]
[10]
Leger J, Ruiz JC, Guibourdenche J, Kindermans C, Garabedian M, Czernichow P. Bone mineral density and metabolism in children with congenital Hypothyroidism after prolonged L-thyroxine therapy. Acta Paediatr 1997; 86(7): 704-10.
[http://dx.doi.org/10.1111/j.1651-2227.1997.tb08572.x] [PMID: 9240877]
[11]
Reinehr T, Roth CL. A new link between skeleton, obesity and insulin resistance: Relationships between Osteocalcin, Leptin and Insulin resistance in obese children before and after weight loss. Int J Obes 2010; 34(5): 852-8.
[http://dx.doi.org/10.1038/ijo.2009.282] [PMID: 20065970]
[12]
Polgreen LE, Jacobs DR Jr, Nathan BM, Steinberger J, Moran A, Sinaiko AR. Association of Osteocalcin with obesity, Insulin resistance, and cardiovascular risk factors in young adults. Obesity (Silver Spring) 2012; 20(11): 2194-201.
[http://dx.doi.org/10.1038/oby.2012.108] [PMID: 22573135]
[13]
Wei J, Karsenty G. An overview of the metabolic functions of Osteocalcin. Rev Endocr Metab Disord 2015; 16(2): 93-8.
[http://dx.doi.org/10.1007/s11154-014-9307-7] [PMID: 25577163]
[14]
Shea MK, Gundberg CM, Meigs JB, et al. γ-carboxylation of Osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 2009; 90(5): 1230-5.
[http://dx.doi.org/10.3945/ajcn.2009.28151] [PMID: 19776145]
[15]
Bassett JH, Williams GR. Role of Thyroid hormones in skeletal development and bone maintenance. Endocr Rev 2016; 37(2): 135-87.
[http://dx.doi.org/10.1210/er.2015-1106] [PMID: 26862888]
[16]
Tsevis K, Trakakis E, Pergialiotis V, et al. The influence of Thyroid disorders on bone density and biochemical markers of bone metabolism. Horm Mol Biol Clin Investig 2018; 35(1): 35.
[http://dx.doi.org/10.1515/hmbci-2018-0039] [PMID: 30218603]
[17]
Navikala K, Vasudha K, Kalra P, Radhika K. Can serum osteocalcin level be used as a marker to assess bone remodeling status in hyperthyroidism? Int J Biochem Res Rev 2016; 10: 1-9.
[http://dx.doi.org/10.9734/IJBCRR/2016/23450]
[18]
Kindblom JM, Ohlsson C, Ljunggren O, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009; 24(5): 785-91.
[http://dx.doi.org/10.1359/jbmr.081234] [PMID: 19063687]
[19]
Redford C, Vaidya B. Subclinical hypothyroidism: Should we treat? Post Reprod Health 2017; 23(2): 55-62.
[http://dx.doi.org/10.1177/2053369117705058] [PMID: 28406057]
[20]
Azim S, Nasr C. Subclinical hypothyroidism: When to treat. Cleve Clin J Med 2019; 86(2): 101-10.
[http://dx.doi.org/10.3949/ccjm.86a.17053] [PMID: 30742580]
[21]
Javed Z, Sathyapalan T. Levothyroxine treatment of mild subclinical Hypothyroidism: A review of potential risks and benefits. Ther Adv Endocrinol Metab 2016; 7(1): 12-23.
[http://dx.doi.org/10.1177/2042018815616543] [PMID: 26885359]
[22]
Saleem U, Mosley TH Jr, Kullo IJ. Serum Osteocalcin is associated with measures of Insulin resistance, Adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 2010; 30(7): 1474-8.
[http://dx.doi.org/10.1161/ATVBAHA.110.204859] [PMID: 20395593]
[23]
Zoch ML, Clemens TL, Riddle RC. New insights into the biology of Osteocalcin. Bone 2016; 82: 42-9.
[http://dx.doi.org/10.1016/j.bone.2015.05.046] [PMID: 26055108]
[24]
Meier C, Beat M, Guglielmetti M, Christ-Crain M, Staub JJ, Kraenzlin M. Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: A randomized controlled trial. Osteoporos Int 2004; 15: 209-16.
[http://dx.doi.org/10.1007/s00198-003-1527-8]
[25]
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and β-cell function from fasting Plasma Glucose and Insulin concentrations in man. Diabetologia 1985; 28(7): 412-9.
[http://dx.doi.org/10.1007/BF00280883] [PMID: 3899825]
[26]
Gouveia CH, Schultz JJ, Bianco AC, Brent GA. Thyroid hormone stimulation of Osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms. J Endocrinol 2001; 170(3): 667-75.
[http://dx.doi.org/10.1677/joe.0.1700667] [PMID: 11524248]
[27]
Yeap BB, Chubb SA, Flicker L, et al. Reduced serum total Osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia and triglyceride levels. Eur J Endocrinol 2010; 163(2): 265-72.
[http://dx.doi.org/10.1530/EJE-10-0414] [PMID: 20501596]
[28]
Polovina S, Popovic V, Duntas L, Milic N, Micic D. Frax score calculations in postmenopausal women with subclinical hypothyroidism. Hormones (Athens) 2013; 12(3): 439-48.
[http://dx.doi.org/10.1007/BF03401309] [PMID: 24121385]
[29]
Saggese G, Bertelloni S, Baroncelli GI, Costa S, Ceccarelli C. Bone mineral density in adolescent females treated with L-thyroxine: A longitudinal study. Eur J Pediatr 1996; 155(6): 452-7.
[http://dx.doi.org/10.1007/BF01955180] [PMID: 8789760]
[30]
Ross DS, Ardisson LJ, Nussbaum SR, Meskell MJ. Serum Osteocalcin in patients taking L-thyroxine who have subclinical hyperthyroidism. J Clin Endocrinol Metab 1991; 72(2): 507-9.
[http://dx.doi.org/10.1210/jcem-72-2-507] [PMID: 1991818]
[31]
Lecomte P, Lecureuil N, Osorio-Salazar C, Lecureuil M, Valat C. Effects of suppressive doses of levothyroxine treatment on sex-hormone-binding globulin and bone metabolism. Thyroid 1995; 5(1): 19-23.
[http://dx.doi.org/10.1089/thy.1995.5.19] [PMID: 7787428]

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