Thyroxine (T4) and triiodothyronine (T3) hormones regulate heat production and energy utilization, and they are very important for normal growth and development. They also play important roles in regulating various homeostatic mechanisms [
It has been understood that adipose tissue is not only a passive energy reservoir, it is but also an active endocrine tissue. Resistin is an adipocytokine which is considered to have an important role in energy metabolism and is secreted from adipocytes and macrophages. Resistin antagonizes insulin effect and causes insulin resistance especially in obese patients. Resistin is also playing a role in inflammation and is a potential biomarker in cardiovascular and many other diseases [
IGF-1 is a growth factor which is secreted from liver as a response to growth hormone (GH). IGF-1 has many receptors in various tissues and manifests insulin-like effect as well; it functions in many metabolic pathways including energy metabolism [
The aims of the present study were (1) to determine serum resistin, IGF-1, TSH, fT4, lipid, and transaminase levels together in untreated patients with hyper-and hypothyroidism and control groups for the first time and (2) to investigate potential relationship between thyroid function and serum levels of resistin and IGF-1 in HT and HrT patients.
The study consisted of 15 HT patients with ages 20–76, 16 SCHT patients with ages 26–71, 15 HrT patients with ages 22–79, 15 SCHrT patients with ages 26–70, and control group consisting of 17 individuals who were detected as healthy by physical examination and laboratory findings. The total number of volunteers was 78.
The individuals having TSH levels over 5.6
The individuals having TSH levels below 0.34
In patient groups there was no individual who had any systemic disease. None of the patients had treatment concerning thyroid dysfunction.
Detailed histories of individuals included in the study were obtained; follow-up forms were prepared. All of the tests and clinical meanings of the tests performed were explained to the individuals, and their written consents were obtained. The ethical approval of study was given by the Okmeydani Educational and Research Hospital Ethics Committee.
10 mL of blood samples into plain vacuum tubes with gel were obtained after 12 hour fasting. They were centrifuged for 10 min at 2000 ×g. T-Chol, HDL-Chol, AST, ALT, TSH, and fT4 were analyzed on the same day. Undiluted serum samples were seperated into two tubes, and they were stored at −80°C for maximum 6 months. Repetative freezing and thawing were not performed.
Serum T-Chol, HDL-Chol, AST, and ALT levels were determined photometrically in Beckman Coulter AU2700 auto-analyzer (Beckman Coulter Inc., CA, USA); TSH ve fT4 levels were determined in Beckman Coulter UniCel DxI 800 autoanalyzer (Beckman Coulter Inc., CA, USA) by using access high sensitive TSH 3rd generation and access fT4 successively by chemiluminescence method. LDL-Chol levels were calculated by the Friedewald formula. AdipoGen Human Resistin ELISA kit (AdipoGen Inc., Incheon, Korea) was used to determine resistin levels. IGF-1 levels were determined in Siemens Immulite 2000 analyzer (Siemens Healthcare Diagnostics, Deerfield, IL, USA) by solid phase enzyme marked chemiluminescence method.
In order to analyze data SPSS 17.0 ve GraphPad InStat 3.05 packet programs were used. Standart deviations (SD) and means of the Gaussian parameters included in the study were given in terms of groups. Both mean and min-max values and mean ± SD values were presented for the nonGaussian parameters. In comparison of more than two groups that were independent of each other (3 groups and 5 groups), Kruskal-Wallis and one way ANOVA tests were used. The groups which were determined to be different from one another in terms of parameters were compared again in binary groups. The correlation between resistin, IGF-I, and TSH was presented via Spearman’s correlation coefficient. The results were evaluated in 95% confidence and significance in
Of the individuals included in the study were 17 (22%) males and 61 (78%) females. Laboratory findings and demographic properties of total HT, total HrT, and healthy control groups and HT, SCHT, HrT, and SCHrT subgroups were showed in Tables
Comparisons of laboratory findings and demographic characteristics of total HT, total HrT, and healthy control groups.
Parameters | Reference ranges | Total hypothyroid group ( |
Total hyperthyroid group ( |
Control group ( |
---|---|---|---|---|
Age (year) | (—) | 47.84 ± 13.31* | 43.43 ± 15.66 |
37 ± 12.53 |
T-Chol (mg/dL) | 120–200 | 235.13 ± 56.99*† | 162.57 ± 42.04 | 178.41 ± 31.64 |
HDL-Chol (mg/dL) | 35–70 | 56.61 ± 13.39 | 52.17 ± 11.61 | 59.65 ± 14.11 |
LDL-Kol (mg/dL) | <130 | 144.19 ± 48.6*† | 89.9 ± 32.32 | 100.24 ± 26.88 |
AST (U/L) | 0–50 | 41.58 ± 46.12‡ |
23.43 ± 7.72 | 19.06 ± 4.46 |
ALT (U/L) | 0–50 | 43.68 ± 58.49 |
24.47 ± 10.18 | 19.12 ± 9.76 |
TSH ( |
0.34–5.6 | 50.85 ± 75.03*† |
0.089 ± 0.090 |
2.10 ± 1.26 |
fT4 (ng/dL) | 0.58–1.64 | 0.53 ± 0.23* | 2.08 ± 1.20† |
0.83 ± 0.10 |
Resistin (ng/mL) | (—) | 12.66 ± 6.04∞ |
12.19 ± 7.13 |
8.45 ± 2.90 |
IGF-I (ng/mL) | 64–345 | 117.22 ± 52.03†* |
155.17 ± 51.67 | 184 ± 49.73 |
Comparisons of laboratory findings and demographic characteristics of 4 subgroups of patients and healthy control groups.
Parameters | Hypothyroid |
Subclinically hypothyroid |
Hyperthyroid |
Subclinically hyperthyroid |
Control group |
---|---|---|---|---|---|
Age (year) | 46.53 ± 13.98 | 49.06 ± 12.98 | 40.40 ± 17.36 |
46.47 ± 13.66 | 37 ± 12.53 |
T-Chol (mg/dL) | 254.27 ± 63.78 |
217.19 ± 44.6 |
146.47 ± 33.69 | 178.67 ± 44.4$ | 178.41 ± 31.64 |
HDL-Chol (mg/dL) | 56.53 ± 11.75 | 56.69 ± 15.16 | 51.53 ± 14.0 | 52.8 ± 9.06 | 59.65 ± 14.11 |
LDL-Chol (mg/dL) | 163.9 ± 53.91 |
125.69 ± 35.42 |
78.27 ± 22.37 | 101.53 ± 37.06 | 100.24 ± 26.88 |
AST (U/L) | 51.6 ± 58.31* |
32.19 ± 29.76 |
23.2 ± 7.8 | 23.67 ± 7.9 |
19.06 ± 4.46 |
ALT (U/L) | 46.47 ± 56.83 |
41.06 ± 61.75 |
26.9 ± 9.6 | 22.0 ± 10.46 | 19.12 ± 9.76 |
TSH ( |
94.4 ± 89.97 |
10.02 ± 5.31 |
0.05 ± 0.06 |
0.13 ± 0.10€ |
2.10 ± 1.26 |
fT4 (ng/dL) | 0.33 ± 0.14 |
0.73 ± 0.08 |
3.08 ± 0.88 |
1.07 ± 0.28 | 0.83 ± 0.10 |
Resistin (ng/mL) | 13.6 ± 6.25 | 11.76 ± 5.89 |
9.51 ± 5.48 |
14.88 ± 7.73# | 8.45 ± 2.90 |
IGF-I (ng/mL) | 123.7 ± 44.03*† | 111.11 ± 59.35€ |
143.73 ± 54.39 | 166.6 ± 47.87 |
184 ± 49.73 |
Correlations between resistin, IGF-1, and TSH in total HT and total HrT groups and HT-HrT subgroups.
IGF-1 | TSH | ||
---|---|---|---|
Total hyperthyroid group |
Resistin |
|
|
IGF-I | — |
|
|
| |||
Total hypothyroid group |
Resistin |
|
|
IGF-1 | — |
|
|
| |||
Hypothyroid subgroup |
Resistin |
|
|
IGF-I | — |
|
|
| |||
Hyperthyroid subgroup |
Resistin |
|
|
IGF-I | — |
|
|
| |||
Subclinically hypothyroid subgroup | Resistin |
|
|
IGF-I | — |
|
|
| |||
Subclinically hyperthyroid subgroup | Resistin |
|
|
IGF-I | — |
|
Within and between assay variations of resistin and IGF-1 measurements.
Concentration | SD | CV | |
---|---|---|---|
Resistin (ng/mL) | |||
| |||
Within assay | 12.57 | 0.47 | 3.73 |
Between assay | 15.32 | 1.07 | 6.97 |
| |||
IGF-1 (ng/mL) | |||
| |||
Within assay | 169 | 6.5 | 3.8 |
Between assay | 169 | 9.1 | 5.4 |
Significantly higher T-Chol and LDL-Chol levels in total HT group were observed in comparison to total HrT and control groups. Significantly higher T-Chol and LDL-Chol levels in HT subgroup were observed in comparison to HrT, SCHrT, and control groups. These parameters were also significantly higher in SCHT in comparison to HrT subgroup. These findings support the possible correlation between thyroid function and lipid metabolism.
Serum AST levels in total HT and HT groups were detected as significantly higher in comparison to control group. Hepatocellular damage due to fatty liver caused by hypercholesterolemia in hypothyroid patients causes high AST levels. Our findings are consistent with this situation.
Thyroid gland and adipose tissue functions are closely correlated with each other. Recently by the discovery of endocrine functions of adipose tissue, it has been considered that adipose tissue not only has storage function but also has active regulatory functions in energy metabolism [
Changes in thyroid hormone levels have been clearly known to affect insulin secretion and sensitivity. Correlation between resistin and thyroid functions have been investigated by both human and animal studies. Syed et al. [
In order to enlighten functions of resistin in human it is neccessary to accomplish detailed studies. There is very little information about relationship between thyroid functions and resistin. Furthermore existing studies present conflicting results [
Significantly higher resistin levels in total HT and total patient group were observed in comparison to control group. It was also observed serum resistin level of total HrT group was higher in comparison to control group. But that elevation was not statistically significant. Serum resistin levels of SCHrT subgroup were significantly higher than those of control group. Although they are not statistically significant, the means of resistin levels in HT, SCHT, and HrT subgroups were higher than those of control group.
The study of Yaturu et al. [
In the study of Krassas et al. [
In another study consisting of 53 hypothyroid patients and 30 controls, Krassas et al. [
In their study consisting of 20 hypothyroid patients and 20 healthy controls, Iglesias et al. [
In this study higher resistin levels in total hypothyroid group conflict in comparison to control group with study of Krassas et al. [
Consequently, when limited number of studies about resistin examined, it was observed that resistin levels are variable in thyroid dysfunctions [
Before now, the correlation between growth hormone excess, insulin resistance, and carbohydrate intolerance has been presented by some studies [
In another study performed with children having GH deficiency, Nozue et al. investigated effect of GH treatment on serum resistin levels [
In this study significantly lower serum IGF-1 levels were detected in total HT group in comparison to total HrT and control groups. Serum IGF-1 levels in HT subgroup were significantly lower in comparison to control group; serum IGF-1 levels in SCHT subgroup were significantly lower in comparison to control group and SCHrT subgroup. A negative correlation between TSH and IGF-1were also observed in HT subgroup. These results were compatible with that of Akin et al. [
In this study, no correlation between resistin and IGF-1 levels was found. The reason may be limited number and age diversity of individuals in study groups. A comparement can not be made about that result because there is no study about correlation between resistin and IGF-1 in thyroid dysfunction in the literature.
In conclusion, increased resistin levels are directly related to thyroid dysfunction, and changes in levels of thyroid hormones may affect synthesis and/or secretion of resistin in adipose tissue and/or macrophages. In addition, serum IGF-1 levels decrease in hypothyroid status and correlate negatively with TSH levels. GH/IGF-1 axis may be influenced in clinical or subclinically hypothyroid patients. However, it was concluded that demographic characteristics, therapeutic variations and underlying reasons of thyroid dysfunction should be taken into consideration while interpreting the resistin and IGF-1 levels in thyroid dysfunction.
The authors of the paper do not have a direct financial relation with the commercial identity mentioned in their paper that might lead to conflict of interests for any of the authors.