Manuscript accepted on :September 19, 2017
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Hemoglobin, Vitamin D, and Lipids in Subclinical Hypothyroid Patients – Do the Anti -Thyroid Autoantibodies Titer Matters?
Jaseem T1, Anupama Hegde1, Chakrapani M2 and Sathish Rao2
1Department of Biochemistry, Kasturba Medical College, Manipal University, Mangaluru, India.
2Department of Internal Medicine, Kasturba Medical College, Manipal University, Mangaluru, India.
Corresponding Author E-mail: email@example.com
Hashimoto's thyroiditis, the commonest cause of hypothyroidism has been proposed as a risk factor for atherosclerosis independent of thyroid function. The aim of this study was to investigate whether Hashimoto's thyroiditis validated by their anti-TPO positivity have any effect on hyperlipidemia, Hemoglobin, vitamin D independent of thyroid function in newly diagnosed subclinical hypothyroid patients (SCH) subjects with TSH < 10µIU/ml. 40 newly diagnosed SCH and 40 healthy euthyroid controls were included in this study. Based on anti-TPO status, the SCH subjects was divided into TPO positive and negative groups. Serum lipid, hemoglobin and vitamin D levels were determined and compared between among the TPO positive and negative SCH subjects. Subjects with and without anti-TPO had significant differences in levels of low-density lipoprotein, total cholesterol, and nonHDL cholesterol. In correlation analysis, anti-TPO showed statistically significant association with Hb, LDL and vitamin D. Subclinical hypothyroidism with thyroid autoimmunity is associated with a marginal decrease in hemoglobin and elevation in LDL. Whether this holds, any bearing on promoting cardiovascular risk needs to be considered further
Anti -Thyroid Autoantibodies; Hemoglobin; Lipids; Subclinical Hypothyroidism; Vitamin DDownload this article as:
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Jaseem T, Hegde A, Chakrapani M, Rao S. Hemoglobin, Vitamin D, and Lipids in Subclinical Hypothyroid Patients – Do the Anti -Thyroid Autoantibodies Titer Matters?. Biomed Pharmacol J 2017;10(3).
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Jaseem T, Hegde A, Chakrapani M, Rao S. Hemoglobin, Vitamin D, and Lipids in Subclinical Hypothyroid Patients – Do the Anti -Thyroid Autoantibodies Titer Matters?. Biomed Pharmacol J 2017;10(3). Available from: http://biomedpharmajournal.org/?p=16793
Subclinical hypothyroidism (SCH) is a common finding discovered during routine thyroid function testing, which is more prevalent than overt dysfunction reaching up to 10-20% worldwide. (1-3) In iodine-replete areas, hypothyroidism is most commonly caused by Hashimoto’s thyroiditis (HT).(4) In HT the immune system attacks the thyroid gland and the resulting inflammation often lead to an underactive thyroid gland. (5) The key biochemical characteristic of HT is the presence of thyroid peroxidase antibody (anti-TPO) in 90-95% subjects. (6) An elevated anti-TPO is reported in 70-80% of SCH subjects. (4)
HT is an independent cardiovascular risk factor in the overt hypothyroid state. (7) SCH with elevated anti-TPO has an increased risk of progression to overt state reinforces its measurement, whether elevated titers influence metabolic markers independent of thyroid function is not clear. The current study was designed to assess the impact of elevated anti-TPO on hemoglobin, vitamin D and lipids in subclinical hypothyroid subjects.
Materials and Methods
A total of 40 newly diagnosed SCH subjects with (TSH<10µIU/ml) and FT4 levels in the normal range and 40 healthy subjects as the control group (group 1) were included in the study. Based on cut-off for positive anti-TPO titer as 34 IU/ml, the patients in the subclinical hypothyroid group were divided into TPO –VE (group 2) and positive +VE (group 3). Patients on medications affecting thyroid function, diabetes mellitus, vitamin supplements and current or previous pregnancy in the last 2 years were excluded from the study. Written informed consent was obtained from all subjects enrolled. The institutional ethical committee approved the work.
Fasting Serum TSH, T3, T4, FT4, anti-TPO, Total cholesterol (TC), High-density lipoprotein (HDL), Triglycerides (TG), low-density lipoprotein (LDL), nonHDL cholesterol (N-HDL-C) Vitamin-D were determined in all subjects using Roche kits in fully automated biochemistry analyzer by the electrochemiluminescence assay (ECLIA).Hb was estimated by Beckman coulter.
All parameters were expressed as Mean ± SD. Statistical analysis was performed by ANOVA followed by Tukey’s multiple comparison test. Correlation of anti- TPO with study parameters analysis by spearman’s correlation. A ‘p‘ value less than 0.05 was considered statistically significant.
Comparison of thyroid profile and study parameters between the study groups, summarized in Table.1 and Table.2 respectively. There was no significant difference in any of the estimated parameters except for TSH between group 1 and 2. TC, LDL, N-HDL-C was significantly higher in patients with elevated anti-TPO (Group 3) than the healthy controls (Group 1). When compared between anti-TPO positive and negative cases (group 2 v/s group 3), TC, LDL, N-HDL was found significantly higher in-group 3. A significant reduction in hemoglobin was observed only in-group 3. Correlations between anti-TPO and other study parameters were summarized in Table 3. Anti-TPO showed a significant positive correlation with LDL and a negative correlation with Vit-D and Hb in the subclinical hypothyroid group.
Table 1: Thyroid profile in Anti-TPO Antibody Negative (TPO – VE), anti-TPO Antibody Positive (TPO + VE) subclinical hypothyroid subjects, and control group
|Parameters||Group 1 control||Group 2 TPO – VE
(< 34 IU/ml ) SCH Subjects
|Group 3 TPO + VE
( ≥ 34 IU/ml ) SCH Subjects
|Age (yrs.)||36 ± 9||34 ±10||34 ± 9|
|TSH (μIU/ml)||2.12 ± 0.78||6.18 ± 1.4||6.10 ± 1.3|
|FT4 (ng/dl)||1.2 ± 0.35||1.1 ± 0.18||1.0 ± 0.25|
|T4 (µg/dL)||7.8 ±1.09||7.6 ± 1.3||7.2 ± 1.5|
|Anti-TPO (IU/ml)||9.8(5.4- 12.7) #||214(107-475) #|
Values represented as mean±SD and #median and interquartile range. Statistical analysis was performed by ANOVA followed by Tukey’s multiple comparison test. * P< 0.05 Group 1 Vs Group 3; # P< 0.05 Group 2 Vs Group 3. T3 -free triiodothyronine; T4-thyroxine; FT4-Free thyroxine; TSH-Thyroid stimulating hormone; TPO Ab – Anti-Thyroid Peroxidase Antibodies.
Table 2: Study Parameters between Anti-TPO Negative (TPO – VE) and Anti-TPO Positive (TPO + VE) cases of subclinical hypothyroid subjects and control group
|Parameters||Group 1 Control||Group 2 TPO – VE
(< 34 IU/ml ) SCH Subjects)
|Group 3 TPO + VE
( ≥ 34 IU/ml ) SCH Subjects
|HB (g/dl)||13.5 ± 1.3||12.9 ± 1.1||12.4 ± 1.1 *|
|TC (mg/dl)||175 ± 23||173 ± 33||194 ± 30 * †|
|TG (mg/dl)||102 ± 37||105 ± 42||108 ± 23|
|HDL (mg/dl)||48 ± 12||47 ± 11||45 ± 16|
|LDL (mg/dl)||112 ± 22||119 ± 34||138 ± 24 * †|
|N-HDL-C (mg/dl)||127 ± 22||126 ±32||149± 31 * †|
|Vitamin – D (ng/ml)||17.3 ± 11||16.2 ± 6.5||14.1 ± 6.3|
Values represented as mean + SD. Statistical analysis was performed by ANOVA followed by Tukey’s multiple comparison test. * P< 0.05 Group 1 Vs Group 3; † P< 0.05 Group 2 Vs Group 3. Hb- hemoglobin ; TC – total cholesterol; LDL-C-low-density lipoprotein cholesterol; HDL-C – high-density lipoprotein cholesterol; TG – triglyceride; N-HDL-C- Non HDL cholesterol. TPO Ab – Anti-Thyroid Peroxidase Antibodies; Vit-D -vitamin D.
In the current study SCH subjects with and without autoimmunity as categorized by the presence of anti-TPO, titers were enrolled to compare their thyroid profile and metabolic parameters. Findings related to lipid parameters in SCH are highly inconsistent in earlier studies with values either higher or similar to the euthyroid group.(8-10) Earlier studies have reported that thyroid autoimmunity may have effects on hyperlipidemia independent of thyroid function. (11, 12) Whereas Mazaheri et al (13) observed lipid alterations in relation to autoimmunity only in subjects with anti-TPO levels higher than 1000 IU/ml. In this study, TC, LDL, and N-HDL-C levels of TPO (+) patients were found to be significantly higher when compared to TPO (-) cases and controls (Table 2).
Current guidelines endorse the assessment of thyroid status in the work-up of anemia (14, 15) Hypothyroidism adversely affects hematological system causing anemia by its effects on erythropoiesis. (16, 17) The frequency of anemia in SCH is as high as that in the overt state. In the present study, the mean Hb percentage was significantly decreased in TPO (+) SCH (Table 2). Wang et al (18) have also reported significantly severe Hb deficiency in Anti-TPO positive patients.
There has been growing evidence of the relationship between vitamin D insufficiency and autoimmune thyroid diseases.(19) We observed lower mean vitamin D levels in TPO (+) SCH, however, the difference did not reach statistical significance. Studies (20, 21) have reported a higher prevalence (92%) of vitamin D insufficiency in HT and its correlation with anti-TPO. In contrast, studies (22, 23) hypothesized that vitamin D deficiency can trigger the autoimmune process resulting in the pathogenesis of underactive thyroid condition. Randomized placebo-controlled trials demonstrated the ameliorative effects of vitamin D supplementation on anti-TPO in autoimmune thyroiditis. (24,25) Even though the exact mechanisms responsible were not clear, the results highlighted the beneficial effects of vitamin D supplementation in attenuation of the risk and adverse outcomes. SCH groups 2 and 3 were merged and analyzed. (Table 3) anti-TPO showed a significant negative correlation with Hb, vitamin D and a positive correlation with LDL.
Table 3: Correlation of anti- TPO with study parameters in subclinical hypothyroid subjects (n=40)
|Vitamin – D (ng/ml)||-0.476||0.002*|
T3 -free triiodothyronine; T4-thyroxine; FT4-Free thyroxine; TSH-Thyroid stimulating hormone; Hb- hemoglobin ; TC – total cholesterol; LDL-C-low-density lipoprotein cholesterol; HDL-C – high-density lipoprotein cholesterol; TG – triglyceride; N-HDL-C- Non HDL cholesterol. TPO Ab – Anti-Thyroid Peroxidase Antibodies; Vit-D -vitamin D. * ‘p‘ value less than 0.05.
The current study differs from the earlier studies with respect to the TSH cutoff considered for SCH (4.12-9.9 μIU/ml) and recruitment of relatively young subjects. The primary limitation of this study is the small sample size and measurement of anti-TPO in euthyroid subjects would have added further information on thyroid autoimmunity.
Earlier studies showed that patients with autoimmune-mediated clinical and subclinical hypothyroidism display significantly elevated circulating inflammatory markers, (26,27) Oxidative stress markers, (28) Lipid Parameters and Lipoprotein (a), (29) carotid intima-media thickness (CIMT) (30) Insulin and obesity (11) suggesting that, autoimmune processes by itself may employ a major impact on endothelial dysfunction. We believe that the combined results of earlier studies on and the present work, provide compelling evidence for the association of elevated anti-TPO with intermediate cardiovascular risk biomarkers. This would be an indication for therapy with levothyroxine replacement and its effects on these biomarkers.
Subclinical hypothyroidism with thyroid autoimmunity is associated with a marginal decrease in hemoglobin and elevation in LDL. Whether this holds, any bearing on promoting cardiovascular risk needs to be considered further
The authors thank all the patients and hospital staffs for their cooperation during the study.
Conflict of Interest
Authors declare that they have no conflict of interest.
- Canaris GJ,Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.
- Surks MI,Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004;291:228-38.
- Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian J Endocrinol Metab 2011;15:78-81.
- Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 2012;22:1200-35.
- Zaletel, K. Determinants of thyroid autoantibody production in Hashimoto’s thyroiditis. Expert Rev Clin Immunol 2007;3:217-23.
- Erdogan M, Erdem N, Cetinkalp S, et al. “Demographic, clinical, laboratory, ultrasonographic, and cytological features of patients with Hashimoto’s thyroiditis: results of a university hospital of 769 patients in Turkey.”Endocrine 2009;36:486-90.
- Mohammed NA, Rawhia E, Akram D, et al. Hashimoto thyroiditis is an independent cardiovascular risk factor in clinically hypothyroid patients. Alexandria Journal of Medicine 2011;47:267–76.
- Peppa M, Betsi G, Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids. 2011;2011:1-9.
- Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007;CD003419.
- Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J 2011;5:76-84.
- Tamer G, Mert M, Tamer I, Mesci B, Kilic D, Arik S. Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia. Endokrynol Pol 2011;62:421-8.
- Topaloglu O, Gokay F, Kucukler K, Burnik FS, Mete T, Yavuz HC, Berker D, Guler S. Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status? Endocrine 2013;44:145-51.
- Mazaheri T, Sharifi F, Kamali K. Insulin resistance in hypothyroid patients under Levothyroxine therapy: a comparison between those with and without thyroid autoimmunity. J Diabetes Metab Disord 2014;13:103.
- Erdogan M, Kösenli A, Ganidagli S, Kulaksizoglu M. Characteristics of anemia in subclinical and overt hypothyroid patients. Endocr J 2012;59:213-20.
- M’Rabet-Bensalah K, Aubert CE, Coslovsky M, Collet TH, Baumgartner C, den Elzen WP, et al. Thyroid dysfunction and anemia in a large population-based study. Clin Endocrinol (Oxf) 2016;84:627-31.
- Haamid B, Mohammad HB, Sheikh S, Rabia F, Rabia H, Sabhiya M. Hypothyroidism: its screening and management and role in erythrocyte abnormalities: a systematic review. Int J Med Pharm Sci. 2013;03:18-24
- Golde DW, Bersch N, Chopra IJ, Cline MJ. Thyroid hormones stimulate erythropoiesis in vitro. Br J Haematol 1977;37:173-7.
- Wang YP, Lin HP, Chen HM, Kuo YS, Lang MJ, Sun A. Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels in patients with anti-thyroid autoantibodies. J Formos Med Assoc 2014;113:155-60.
- Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, Szekanecz Z, Langevitz P, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8:243-7.
- Tamer G, Arik S, Tamer I, Coksert D. Relative vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid. 2011;21:891-6.
- Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J.2014;55:476-81.
- Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J Nucl Med. 2015; 18(3):222-7.
- Bozkurt NC, Karbek B, Ucan B, Sahin M, Cakal E, Ozbek M, Delibasi T. Vitamin D and thyroiditis. J Endocr Pract. 2013;19:479-84.
- Krysiak R, Szkróbka W, Okopień B. The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto’s Thyroiditis and Normal Vitamin D Status. Exp Clin Endocrinol Diabetes.2017. PubMed PMID: 28073128.
- Włochal M, Kucharski MA, Grzymisławski M. The effects of vitamins and trace minerals on chronic autoimmune thyroiditis. Journal of Medical Science. 2016 Feb 17;83:167-72.
- Jublanc C, Beaudeux JL, Aubart F, Raphael M, Chadarevian R, Chapman MJ, Bonnefont-Rousselot D, Bruckert E. Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid disorders: relevance to vascular inflammation. Nutr Metab Cardiovasc Dis. 2011;21:817-22.
- Turemen EE,Cetinarslan B, Sahin T, et al. Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr J.2011; 58:349-54.
- Nanda N, Bobby Z, Hamide A. Oxidative stress in anti thyroiperoxidase antibody positive hypothyroid patient. Asian J Biochem. 2012;7:54-8.
- Yetkin DO, Dogantekin B. The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis. Int J Endocrinol. 2015;2015:952729.
- Ciccone MM, De Pergola G, Porcelli MT, Scicchitano P, Caldarola P, Iacoviello M, Pietro G, Giorgino F, Favale S. Increased carotid IMT in overweight and obese women affected by Hashimoto’s thyroiditis: an adiposity and autoimmune linkage? BMC Cardiovasc Disord. 2010;10:22.