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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 30  |  Issue : 4  |  Page : 197-203

Assessment of serum irisin level in thyroid disorder


Department of Internal Medicine, Endocrinology and Metabolism, Ain Shams University Hospital, Cairo, Egypt

Date of Submission18-Jul-2018
Date of Acceptance26-Jul-2018
Date of Web Publication14-Jan-2019

Correspondence Address:
Bassem M Mostafa
Department of Internal Medicine, Endocrinology and Metabolism, Ain Shams University Hospital, Cairo 11566
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejim.ejim_37_18

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  Abstract 

Background Irisin is a newly discovered myokin secreted by myocytes responsible for transmission of signals from muscles to other body tissues. Irisin improves systemic metabolism by increasing the energy expenditure. Owing to numerous similarities in action between irisin and thyroid hormones it seems imperative to explore these substances’ potential mutual influence on the body.
Objective To estimate serum irisin concentration in patients with hypothyroid and hyperthyroid diseases, and to detect the relation of serum irisin in patients with thyroid disorders with creatine kinase (CK), a serum marker of muscle damage.
Patients and methods The study comprised 30 hyperthyroid patients (group 1), 30 hypothyroid patients (group 2), and 30 normal persons (group 3). Irisin was measured using enzyme-linked immunosorbent assay. Thyroid-stimulating hormone, triiodothyronine, and free thyroxine levels were measured using chemiluminescent microparticle immunoassay technology.
Results Irisin hormone level significantly decreased in hypothyroid patients in comparison with hyperthyroid patients. Irisin hormone level increased in hyperthyroid patients in comparison with normal persons, whereas it decreased in hypothyroid patients in comparison with normal persons. CK level significantly decreased in hyperthyroid patients in comparison with hypothyroid patients. CK level significantly increased in hypothyroid patients in comparison with normal persons, whereas it significantly decreased in hyperthyroid patients in comparison with normal persons.
Conclusion Obtained results suggest the influence of thermometabolic state on irisin level.

Keywords: hyperthyroidism, hypothyroidism, irisin


How to cite this article:
Halawa MR, Abdelsalam MM, Mostafa BM, Ahmed AG. Assessment of serum irisin level in thyroid disorder. Egypt J Intern Med 2018;30:197-203

How to cite this URL:
Halawa MR, Abdelsalam MM, Mostafa BM, Ahmed AG. Assessment of serum irisin level in thyroid disorder. Egypt J Intern Med [serial online] 2018 [cited 2019 Jun 24];30:197-203. Available from: http://www.esim.eg.net/text.asp?2018/30/4/197/249961




  Introduction Top


Myokines are specifically defined as cytokines or other peptides that are produced, expressed, and released by muscle fibers and that exert endocrine effects [1].

Irisin is a hormone induced with exercise from the skeletal muscles in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure with no changes in the movement or food intake. This results in improvements in obesity and glucose homeostasis [1].

Irisin improves systemic metabolism by increasing the energy expenditure. Irisin have a significant influence on the body metabolism and thermogensis by acting on adipose tissue and promoting a phenomenon called white adipose tissue browning. Whereas, white adipose tissue is the primary site of triglycerides storage, brown adipose tissue is specialized in energy expenditure to maintain body temperature in a cold environment. Brown adipose tissue oxidizes fatty acids and generates heat by the mitochondrial uncoupling protein [2].

Irisin has also potential antiobesity effects. When irisin levels rise through aerobic exercise the hormone switches on genes that convert white fat into good brown fat. This is beneficial because brown adipose tissue continues to burn off more calories. This helps people to maintain a healthy BMI and avoid obesity [3].

There are other recognized factors that also influence metabolic state, such as thyroid hormones [thyroxine (free T4) and metabolically active triiodothyronine (free T3)] that increase heat production and control the energy balance by stimulating numerous metabolic pathways including the increase on brown adipose tissue mass. Also thyroid hormones increase oxidative phosphorylation and oxygen consumption [4].

Owing to numerous similarities in action between irisin and thyroid hormones it seems imperative to explore these substances’ potential mutual influences on the body.


  Aim Top


Detect relation between serum irisin and thyroid disorders with serum creatine kinase (CK) as a marker of muscle damage.


  Patients and methods Top


Type of study

Case control study.

Patients

This study was conducted on 90 Egyptian patients. They were selected from the outpatient’s clinic of Ain Shams University Hospital. The patients were classified into the following.

Group 1 included 30 hyperthyroid patients; nine males and 21 females. Group 2 included 30 hypothyroid patients; seven males and 23 females. Group 3 included 30 healthy volunteers; 13 males and 17 females.

Methods

Both patients and controls were subjected to the following. Full medical history with emphasis in taking (age, duration of the disease, drug intake, and physical exercise); thorough medical examination (height, weight, and BMI); complete evaluation of thyroid functional state [thyroid-stimulating hormone (TSH), free T3, free T4, and thyroid ultrasound examination]; measurement of fasting serum irisin hormone and measurement of serum CK; and lactate dehydrogenase (LDH).

Measurement of fasting serum irisin

Name

Human Irisin ELIZA Kit (2015; SunLong Biotech, China).

Sample preparation

In our study we collected blood after overnight fasting (6–8 h) and allowed samples to clot for 30 min before centrifuging for 15 min at ∼1000g, then samples were stored at −20°C for a month till the time of assay.

Principle of irisin assay

This assay is a competitive enzyme-linked immunosorbent assay for quantitative determination of irisin in human biological fluids (plasma, serum, cell culture supernatant). A polyclonal antibody recognizing native irisin reacts with a series of predetermined recombinant irisin standard proteins or samples under competition in the irisin-coated plate. Their relative reactivity is plotted with that of the standard proteins (normal values, 0.50–30 ng/ml).

Measurement of creatine kinase

Name

Sigma-Aldrich, India (Ref.: MAK116).

Sample preparation

In our study we used blood samples and assayed them directly.

Priniciple of assay

This reaction can be carried out at either room temperature or 37°C. Bring all components to room temperature or 37°C before use. Prepare enough of the Reconstituted Reagent for each sample to be tested. Each sample requires 100 ml of Reconstituted Reagent. Transfer 10 ml of samples into separate wells. Add 100 ml of the Reconstituted Reagent to each sample well and tap plate to mix. Incubate the samples at either room temperature or 37°C. After 20 min, take the initial absorbance measurement at 340 nm (A340) initial. Note: CK is fully activated within 20 min by the glutathione present in the substrate solution. Continue to incubate the plate at either room temperature or 37°C for 20 additional minutes (normal value, 0–171 U/l).


  Results Top


Ninety persons participated in the study. All are age and sex matched. They were divided into three groups: group 1: includes 30 hyperthyroid patients, nine (30%) males and 21 (70%) females ([Table 1]). Their mean age was 40.6±12.5 years. Their mean height was 165.8±7.7 cm. Their mean weight was 76.3±10.8 kg and their mean BMI was 27.7±3.4 kg/m2 ([Table 2]). Group 2: includes 30 hypothyroid patients, seven (23.3%) males and 23 (76.7%) females ([Table 1]). Their mean age was 40.5±12.7 years. Their mean height was 164.8±7.3 cm. Their mean weight was 95.8±9.3 kg and their mean BMI was 35.2±3.01 kg/m2 ([Table 2]). Group 3: includes 30 persons as control group, 13 (43.3%) males and 17 (56.7%) females ([Table 1]). Their mean age was 41.5±15.5 years. Their mean height was 166.7±8.7 cm. Their mean weight was 75.4±12.4 kg and their mean BMI was 27.2±3.2 kg/m2 ([Table 2]).
Table 1 Comparison of Gender between studied groups (using chi-square test)

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Table 2 Comparison of demographic and Anthropometric Measurements between studied groups (using ANOVA and Post Hoc test)

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There was a highly significant difference between the studied groups with respect to TSH, free T3, and free T4 (P<0.01). Post-hoc test reveals that there was a highly significant difference between normal and hyperthyroid groups, hyperthyroid and hypothyroid groups with respect to TSH, free T3, and free T4 (P<0.01) and a highly significant difference between normal and hypothyroid groups with respect to TSH (P<0.01) ([Table 3]).
Table 3 Comparison of TSH, Free T3 and Free T4 between studied groups using ANOVA and Post Hoc test)

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There is a high significant difference between the studied groups with respect to thyroid ultrasound findings (P<0.01); in hyperthyroid patients (46.7%), show multinodular goiter, whereas 33.3% show generalized enlargement, and 20.0% show normal gland finding; in hypothyroid patients, 26.7% show multinodular goiter; whereas the majority (73.3%) show normal gland finding, and 100.0% of controls show normal gland by thyroid ultrasound ([Table 4]).
Table 4 Comparison of thyroid Ultrasound between studied groups (using Chi-square test).

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There was a high significant difference between the studied groups with respect to CK, LDH, and irisin (P<0.01). Post-hoc test reveals that there was a highly significant difference between normal and hypothyroid groups, hyperthyroid and hypothyroid groups, and normal and hyperthyroid groups with respect to CK (P<0.01). In addition to that; there was a high significant difference between normal and hyperthyroid groups and normal and hypothyroid groups with respect to LDH (P<0.01). Moreover, there was a high significant difference between normal and hypothyroid groups and hyperthyroid and hypothyroid groups with respect to irisin (P<0.01) ([Table 5]).
Table 5 Comparison of CK, LDH and Irisin between studied groups (using ANOVA and Post Hoc test)

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Comparing all of the studied parameters between hyperthyroidism and normal, there was a high significant difference of TSH, free T3, free T4, CK, and LDH between hyperthyroid group and normal group (P<0.01) ([Table 6]).
Table 6 Comparison of all studied parameters between hyperthyroidism and normal (student-test)

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Comparing all of the studied parameters between hypothyroidism and normal. There was a high significant difference of TSH, CK, and LDH between hypothyroid group and normal group (P<0.01) ([Table 7]).
Table 7 Comparison of all studied parameters between hypothyroidism and normal (student-test)

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Our correlation study with irisin in hyperthyroid group found a high significant negative correlation with TSH, weight, BMI, and CK (P<0.01), whereas there is a high significant positive correlation with free T3 and free T4 ([Table 8]).
Table 8 Shows Correlation between (TSH, Free T3, Free T4, CK, LDH, Age, Weight, Height and BMI) and Irisin in Patients with Hyperthyroidism (Using Pearson Correlation Coefficient)

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Our correlation study with irisin in hypothyroid group found a significant positive correlation with LDH (P<0.05) ([Table 9]), whereas there was insignificant correlation between irisin and other studied variables in the control group (P>0.05) ([Table 10]).
Table 9 Correlation between Irisin and (TSH, Free T3, Free T4, CK, LDH, Age, Weight, Height and BMI) in Patients with Hypothyroidism (Using Pearson Correlation Coefficient)

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Table 10 Correlation between Irisin and (TSH, Free T3, Free T4, CK, LDH, Age, Weight, Height and BMI) in controls (Using Pearson Correlation Coefficient)

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With respect to the multiple linear regression analysis, it displays that CK are independent predictor of serum irisin in patients (hyperthyroid and hypothyroid) ([Table 11]).
Table 11 Regression analysis showing independent predictors for Serum Irisin in patients (Hyper and Hypothyroid) (Using Multiple Linear Regression analysis)

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  Discussion Top


Irisin is a newly discovered myokin secreted by myocytes responsible for transmission of signals from muscles to other body tissues [5].

Irisin improves systemic metabolism by increasing energy expenditure. Irisin have a significant influence on the body metabolism and thermogensis by acting on adipose tissue and promoting a phenomenon called white adipose tissue browning. Whereas, white adipose tissue is the primary site of triglycerides storage, brown adipose tissue is specialized in energy expenditure to maintain the body temperature in a cold environment. Brown adipose tissue oxidizes fatty acids and generates heat by the mitochondrial uncoupling protein [2].

Irisin has also a potential antiobesity effect. When irisin levels rise through aerobic exercise the hormone switches on genes that convert white fat into good brown fat. This is beneficial because brown adipose tissue continues to burn off more calories. This helps people to maintain a healthy BMI and avoid obesity [3].

There are other recognized factors that also influence metabolic state, such as thyroid hormones (free T4 and metabolically active free T3), which increase heat production and control the energy balance by stimulating numerous metabolic pathways including the increase on brown adipose tissue mass [4]. Also thyroid hormones increase oxidative phosphorylation and oxygen consumption [6].

The aim of this study is the evaluation of serum irisin concentration in patients with thyroid dysfunction and its correlation with CK levels as a serum marker of muscle damage.

Our study showed that hyperthyroid patients had higher irisin level (26.83±7.95 pg/ml) than hypothyroid patient (16.60±4.07 pg/ml) with a high significant difference (P<0.01).

These results are in agreement with those reported by Ruchala et al. [7] who studied 10 patients with hypothyroidism and 10 patients with hyperthyroidism, and found that irisin is lower in hypothyroid patients compared with hyperthyroid patients with a bordering statistical significance of P=0.0725. Lower irisin hormone level found in patients with hypothyroidism might be explained with muscles destruction, however the higher level of irisin in hyperthyroidism might be explained by hypermetabolic state.

In our results we found CK level were significantly higher in hypothyroid patients (196.26±4.53 μ/l) when compared with hyperthyroid patients (33.80±1.49 μ/l) with a high statistical significance (P<0.01).

High CK found in hypothyroidism may be explained by muscle destruction characteristic of hypothyroidism and therefore irisin is low in hypothyroid patient.

These results agreed with McGrowder et al. [8] who studied serum CK and LDH in 68 hypothyroid patient and 92 hyperthyroid patient and found that CK level were significantly higher in hypothyroid patients when compared with hyperthyroid patients (P=0.0004) as hypometabolic state of hypothyroidism, which can cause a reduction in glycolysis and oxidative phosphorylations and thus reduce ATP concentrations beyond a critical limit. The alteration in sarcolemmal membranes can cause increased cell permeability and the leakage of CK from cells. Another possibility is reduced turnover of CK because of hypothyroidism allowing serum activities to rise generating a marked release of CK through the altered sarcolemmal membranes. Hypermetabolic state in hyperthyroidism increased enzyme degradation, which may have contributed to these low CK activity, so muscle cell is less permeable than normal to efflux of CK. Also agreed with Prakash et al. [9] who studied 30 hypothyroid and 20 hyperthyroid and found CK levels in hyperthyroid patients (54.80±22.30 IU/l) are significantly lower as compared with hypothyroid patients (186.53±34.79 IU/l) Hypothyroid patients have increased concentration of CK, which is mostly due to increased CK-MM.

In our study, LDH increased in both hypothyroid group (245.60±9.64 μ//l) and hyperthyroid group (252.40±7.03 μ/l) with no significant difference (P>0.05). This agreed with McGrowder and colleagues who found that LDH activity was increased in the hypothyroid and hyperthyroid states. This elevations of LDH levels could reflect increased release and/or decreased clearance from the liver.

Our study showed high significant positive correlation between irisin, free T3, and free T4, highly significant negative correlation between irisin, TSH, weight, BMI, and CK (P<0.01), in hyperthyroid patients.

These results agreed with Ruchala et al. [7] who found positive correlation between irisin and free T4 (P=0.036), negative correlation between irisin and CK (P=0.014), this indicate the profound influence of disturbed thyroid function on irisin levels.

Multivariate regression analysis found that CK are independent predictors of serum irisin in hyperthyroid and hypothyroid patients.


  Conclusion Top


Obtained results suggest the influence of thermometabolic state on irisin concentration. Lower irisin hormone level found in patients with hypothyroidism might be explained with muscles destruction demonstrating with high CK levels. However, the higher level of irisin in hyperthyroidism might be explained by hypermetabolic state.

Recommendations

Further in depth studies are needed to study the relationship of irisin with thyroid disorders. Studies needed to demonstrate if treating thyroid diseases and restorating euthyroid state reversed changes in irisin and CK levels. Patients who participated in further studies should be deprived from the treatment for long a period.

Financial support and sponsorship

Nil.

Ethical approval

The study was registered and approved by the local institutional ethical committee and all procedures were in accordance with the standards of 1964 Helsinki Declaration and its later amendments ethical standards. Informed consent was obtained from each participant who were included in the study.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012; 8:457–465.  Back to cited text no. 1
    
2.
Timmons JA, Baar K, Davidsen PK, Atherton PJ. Is irisin a human exercise gene? Nature 2012; 488:E9– E10.  Back to cited text no. 2
    
3.
Boström P, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481:463–468.  Back to cited text no. 3
    
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Lahesmaa M, Orava J, SchalinJäntti C, Soinio M, Hannukainen JC, Noponen T et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab 2014; 99:E28–E35.  Back to cited text no. 4
    
5.
Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L et al. Effects of obesity, diabetes and exercise on FNDC5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol 2014; 592:1091–1107.  Back to cited text no. 5
    
6.
Harper ME, Seifert EL. Thyroid hormone effects on mitochondrial energetics. Thyroid 2008; 18:145–156.  Back to cited text no. 6
    
7.
Ruchala M, Zybek A, Szczepanek‐Parulska E. Irisin − newly discovered adipomyokine and its association with thyroid function − preliminary study. Endocrine Abstracts 2014; 35:996.  Back to cited text no. 7
    
8.
McGrowder DA, Fraser YP, Gordon L, Crawford TV, Rawlins JM. Serum creatine kinase and lactate dehydrogenase activities in patients with thyroid disorders. Niger J Clin Pract 2011; 14:45–49.  Back to cited text no. 8
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9.
Prakash A, Lal AK, Negi KS. Serum creatine kinase activity in thyroid disorders. JK Sci 2007; 9:1.  Back to cited text no. 9
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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Introduction
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Patients and methods
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