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CLINICAL STUDY |
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, N. Plastira 22, Thessaloniki, Greece 551 32, 1 Department of Biological Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2 Department of Epidemiology and Hygiene, Dimokritio University of Thrace, Thrace, Greece and 3 Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece
(Correspondence should be addressed to G E Krassas; Email: krassas{at}the.forthnet.gr)
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Abstract |
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Objectives: To undertake a controlled, prospective study to investigate resistin concentrations in hyperthyroidism before and after restoration of euthyroidism and to correlate the results with body weight, body fat, waist circumference and body mass index (BMI).
Patients and Methods: A total of 43 hyperthyroid patients (12 men and 31 women) were investigated, in addition to 23 controls. Anthropometric parameters and resistin concentrations were measured. All the patients commenced taking antithyroid drugs and 3–4 months later the same investigations were performed in 36 of the 43 individuals.
Results: Hyperthyroid patients exhibited increased resistin concentrations in comparison with controls. Normalization of thyroid hormones was accompanied by a significant decrease in resistin concentration. A sex difference was also found, men showing a significant decrease in resistin concentrations, whereas in women no such difference was found. Resistin concentrations did not correlate with different anthropometric parameters, age and thyroid hormones, either before or after treatment.
Conclusions: This study demonstrates for the first time that, although resistin concentrations are increased in hyperthyroidism, they are not associated with body weight, body fat, waist circumference or BMI, which makes it unlikely that resistin plays a crucial part in thermogenesis and energy homeostasis in thyrotoxic patients.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
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Although the first report proposed that serum concentrations of resistin would be increased in the obese state, a number of later publications have demonstrated decreased expression of the resistin gene in obesity (7). Moreover, genetic variations in the resistin gene did not show any association with obesity or (non-insulin-dependent) type 2 diabetes mellitus in Italian (8) or Japanese (9) populations. In one recent study in humans (10), it was demonstrated that resistin concentrations are not associated with markers of insulin resistance or obesity, and are not regulated by fasting or by the administration of leptin. It was concluded that circulating resistin is unlikely to have a major role in obesity, insulin resistance, or energy homeostasis in humans.
Until now, the role of resistin in human diseases and physiology has remained elusive. It may have a mechanism of action the opposite of that observed for adiponectin. Conceptually, it is interesting that adipose tissue secretes hormones that have both positive and negative effects on hepatic insulin sensitivity (11). To date, very few studies have reported on resistin concentrations in patients with hyperthyroidism before and after normalization of circulating thyroid hormones, and they present conflicting results. In one such study, resistin concentrations were significantly reduced in patients with hyperthyroidism in comparison with those in euthyroid individuals, but attainment of euthyroidism was not accompanied by a significant modification of resistin concentrations. The authors concluded that resistin might be implicated in the insulin-resistant state that accompanies thyrotoxicosis (12). In another report (13), thyrotoxic individuals were investigated who had received radioiodine treatment and became clinically and chemically hypothyroid. Resistin concentrations were measured when the patients were in the thyrotoxic state and after they had become hypothyroid, and were found to be significantly decreased in the latter state.
The aim of this controlled, prospective study was to investigate resistin concentrations in hyperthyroidism – a disease in which weight loss is one of the main manifestations – before and after restoration of euthyroidism, and to correlate the results with body weight, body fat, waist circumference and body mass index (BMI). Such data, to the best of our knowledge, have not been published previously.
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
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Twenty-three euthyroid normal individuals (10 men and 13 women), mean age 47.8 ± 11.4 years (range 24–71 years), matched for age (5-year cohorts), BMI and body fat in the hyperthyroid state, served as controls. In all the control individuals, the same measurements were performed as in the patients.
All anthropometric data for patients and controls are presented in Table 1
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The serum concentrations of tT3, fT4, and TSH were measured by standard, commercial radioimmunoassay kits (Brahms, Henningsdorf, Germany). Normal values of these parameters are presented in Table 1
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The serum concentration of resistin was measured using a commercial enzyme immunoassay kit (Phoenix Pharmaceuticals Inc., Belmond, CA, USA). The assay was performed on 96-well polystyrene platers pre-coated with secondary antibody that can bind to the Fc fragment of the primary antibody; the Fab fragment of the primary antibody binds specifically with resistin. A competitive immunoassay approach was followed, with biotin-labelled resistin: the biotinylated peptide interacts with streptavidin–horseradish peroxidase, which catalyses the peroxidation of the substrate 3,3',5,5'-tetramethylbenzidine, to produce a coloured derivative. The enzymatic reaction was stopped by HCl. A standard curve with known concentrations of resistin was prepared and resistin serum concentrations were determined according to this standard curve. An intra-assay variation of 8.4% was calculated for a sample with a concentration of about 30 ng/ml measured six times in the same assay. An interassay variation of 9.4% was calculated for the same sample measured at six different sessions.
The study was approved by the hospital Ethics Committee and all patients and controls gave informed consent to participate.
Statistical analysis
SSPSS 8.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analyses, and P<0.05 (two-tailed) was considered statistically significant for all analyses. Normality of distribution was tested by the Kolmogorov–Smirnov goodness of fit test. All parameters tested were normally distributed. Comparisons were performed by two-tailed unpaired and paired t-tests. Descriptive statistics are given as mean ± S.D. for all variables. Pearson’s and Kendall’s correlation coefficients were used to evaluate the association between serum resistin concentrations and different anthropometric parameters (body weight, BMI, body fat and waist circumference), the changes (value after treatment minus value before) and the concentrations of thyroid hormones and TSH.
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Results |
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TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
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).
Patients with hyperthyroidism exhibited increased resistin concentrations in comparison with euthyroid control individuals (11.0 ± 6.5 compared with 6.1 ± 3.7 ng/ml, P = 0.002; Table 1, Fig. 1). Normalization of circulating thyroid hormones 3–4 months after the initiation of treatment was accompanied by a significant decrease in resistin concentrations (11.0 ± 6.5 compared with 6.8 ± 4.3 ng/ml, P = 0.006; Table 2); after treatment, resistin concentrations did not differ from those in euthyroid controls (6.8 ± 4.3 compared with 6.1 ± 3.7 ng/ml, P = NS; Table 1, Fig. 1).
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, Fig. 1). Moreover, no differences in resistin concentrations were demonstrated between men and women either before or after treatment.
As expected, significant changes were noted in different anthropometric parameters studied in patients before and after they had attained euthyroidism, and between men and women (Table 2). Finally, resistin concentrations did not correlate with thyroid hormones, different anthropometric parameters or age, either before or after treatment.
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Discussion |
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TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
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To date, there have been only a few studies that have reported on this issue. Iglesias et al. (12) investigated 20 hyperthyroid patients and provided information regarding body weight and BMI before and after treatment of the hyperthyroidism. They demonstrated that patients exhibited significantly reduced resistin concentrations in comparison with euthyroid individuals (6.4 ± 0.8 compared with 8.4 ± 0.7 µg/l, P < 0.05). Normalization of circulating thyroid hormone concentrations was not followed by any significant change in resistin concentrations (5.4 ± 0.7 µg/l, P = NS). After adjustment for BMI, resistin concentrations were similar in hyperthyroid patients and euthyroid individuals. However, normalization of thyroid function produced a significant reduction in resistin concentrations (from 0.28 ± 0.03 to 0.21 ± 0.03 µg/l per unit of BMI; P < 0.05). The main drawbacks of that study were the small number of patients investigated and the lack of measurement of body composition. In another recent study, Yaturu et al. (13) investigated 69 patients with Graves’ disease, 32 of whom were followed after radioiodine treatment when they were hypothyroid, representing a hypothyroid group. The authors found a significant difference in resistin concentrations between that group and those with Graves’ disease (6.37 ± 0.09 compared with 5.81 ± 0.13 ng/ml, P = 0.0001). It should be noted that this was an uncontrolled study, in which measurements of body composition and BMI were not made; moreover, resistin concentrations were compared with those in thyrotoxic patients who became hypothyroid after radioiodine treatment. A further disadvantage of the study is that it is not clear whether paired or unpaired t-tests were used.
The present study is the first to report the effect of hyperthyroidism – a disease in which weight loss is a predominant feature – on resistin concentrations in correlation with BMI and body composition. Although BMI, body weight, waist circumference and body fat were increased after treatment, as expected, no association was found with resistin concentrations, either before or after restoration of thyroid function.
Little is known about the effects of weight loss on resistin regulation. In a recent study (15), it was demonstrated that modest energy restriction and weight loss are not associated with alteration in circulating resistin concentrations in healthy, normal-weight volunteers. These findings are similar to results in obese individuals with insulin resistance who were enrolled in a behaviour-modification programme to induce weight loss (16), and similar to results from healthy lean individuals exposed to caloric deprivation for 2 days (10). In the latter study, it was found that resistin did not correlate with BMI, waist-to-hip ratio, fat mass or insulin resistance.
To the best of our knowledge, no study to date has reported on the effect of weight gain on resistin regulation. Our results suggest that, although resistin concentrations are increased in thyrotoxic patients, this is unlikely to play a major part in energy homeostasis in this group.
Another interesting finding of this study was that thyrotoxic men had a significant difference in resistin concentrations before and after attaining euthyroidism, whereas this was not found in female patients; a sex difference in favour of men was also found by Iglesias et al. (12). These findings are in disagreement with other recent data showing that resistin concentrations exhibit a sexual dimorphism, with women having greater concentrations than men (~20% greater) (10). A change in the metabolic clearance of resistin in hyperthyroidism cannot be excluded, and may explain this sex difference; data on this subject are absent from the literature. Furthermore, a number of hormones and factors such as adiponectin, leptin, tumour necrosis factor-
and others have been discovered recently, which are expressed by adipose tissue and appear to have key roles in thermogenesis and energy metabolism. However, the effect that these peptides may have on circulating concentrations of resistin has not yet been fully identified and may explain, at least in part, the sexual dimorphism with regard to resistin concentrations that is seen in hyperthyroid patients, in favour of men.
In conclusion, this study demonstrates that, although resistin concentrations are increased in hyperthyroidism, they are not associated with BMI, body fat, waist circumference and body weight, which makes it unlikely that resistin plays a crucial part in energy homeostasis in thyrotoxic patients. More studies are needed, with special emphasis on the concentrations of other adipokines and factors, before final conclusions can be drawn regarding the physiological implications and the aetiology of this very interesting finding.
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References |
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TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
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, patients who were followed up; 
, patients in the euthyroid state; , controls.