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Article

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs)

by
Fernanda Velluzzi
1,
Silvia Pisanu
1,
Maura Galletta
2,
Michele Fosci
1,*,
Gianni Secci
1,
Andrea Deledda
1,
Francesco Boi
1,
Rossella Rodia
1,
Giuseppe Fanciulli
3,
Alessandro Palmerio Delitala
3,
Gianmarco Sainas
1 and
Andrea Loviselli
1
1
Endocrinology, and Obesity Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
2
Hygiene Section, Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy
3
Department of Surgical, Medical and Experimental Sciences, University of Sassari-Endocrine Unit, AOU Sassari, 07100 Sassari, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2022, 11(17), 5125; https://doi.org/10.3390/jcm11175125
Submission received: 21 July 2022 / Revised: 6 August 2022 / Accepted: 27 August 2022 / Published: 31 August 2022
(This article belongs to the Section Endocrinology & Metabolism)
Browse Figure
Versions Notes

Abstract

:
A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

1. Introduction

Obesity and overweight are serious health problems. They are major risk factors for non-communicable diseases and have a high prevalence in all parts of the world, including some less-developed regions, especially among middle-aged women [1,2,3]. Subclinical hypothyroidism (SH), which is characterized by normal serum thyroid hormone levels and increased Thyroid-Stimulating Hormone (TSH) values [4,5], is also widespread in the general population [6], especially among middle-aged women [7], and leads to an increased risk of cardiovascular disease [8] and mortality [9]. The association between obesity and SH could determine a further increase in the risk [10]. The assessment of thyroid function in patients with obesity is frequent in clinical practice [11], but the prevalence of altered thyroid function has shown conflicting findings, ranging in particular from 9.7% to 18.9% for overt hypothyroidism and from 9.4% to 20.9% for subclinical hypothyroidism [12]. On this issue, Valdés et al. [13] suggest the use of a wider TSH reference values range for patients with obesity, as the current reference values would triple the prevalence of hypothyroidism among these patients. Likewise, high normal serum TSH levels are associated with higher BMI values in the general Danish population [14], although the findings on this association remain controversial. In fact, this first observation was confirmed by both population-based [15,16,17,18,19,20] and clinical studies [21,22,23,24,25,26,27] among individuals with obesity, but it was not confirmed by several other population-based [28,29,30] and clinical studies [31,32,33,34,35,36]. Moreover, in patients with obesity, the mean serum TSH values have also shown contrasting results: a meta-analysis by Fontenelle et al. [37] reported mean TSH values higher in patients with obesity than in normal-weight individuals in eight studies, but the values were superimposable in another three studies. Furthermore, Knudsen et al., who evaluated a Danish population ten years after they were initially evaluated in 2005 [14], observed that the changes in TSH levels appeared to be positively associated with weight changes [38]. More recently, several studies have been conducted on obese patients treated with bariatric surgery. Juiz Valina et al. evaluated TSH changes at 1, 3, 6, 12, 18, 24, 30, 36, and 42 months after bariatric therapy in 129 obese euthyroid patients and found a significant decrease in TSH values, especially between 6 and 12 months (p < 0.001), of approximately 0.034 units per month of follow-up [39]. In a subsequent study conducted selectively on patients with morbid obesity, the same authors observed a central resistance to thyroid hormones preoperatively, which markedly reduced postoperatively [40]. In a review focused on the effects of bariatric surgery on the alterations of thyroid function in obesity, Cordido et al. suggested that the eventual mild hyperthyrotropinemia may be the consequence of a compensatory response and should be considered non-pathological in the absence of other evidence of reduced thyroid function [41]. It is important to emphasize that highly precise identification of thyroid dysfunction in patients with obesity is not negligible since even a mild thyroid failure or ATAs positivity could increase the risk of cardiovascular diseases [42] or psychopathological disorders [43,44] and make weight loss more difficult [45]. On the other hand, long-term treatment with thyroid hormones in euthyroid patients with obesity does not significantly improve weight loss and may cause adverse effects [46]. In the general adult population, the majority of cases of subclinical and overt hypothyroidism are caused by autoimmune thyroid disease (AITD) [4]. Both obesity [47,48,49,50] and autoimmune thyroid disease [51,52,53] are characterized by low degrees of inflammation, which could favor the onset of one disease on top of the other [54,55,56,57,58]. In a systematic review and meta-analysis, Song et al. confirmed the previously reported link between obesity and thyroid autoimmunity, showing a significant association between obesity and autoimmune hypothyroidism and thyroid peroxidase autoantibodies (TPOAb) [59]. Moreover, it has also been reported that high normal serum TSH values are associated with all-cause mortality and non-fatal cardiovascular events in middle-aged and older overweight women. The authors suggest that this association is probably mediated by the pro-inflammatory state and autoimmune activation affecting the circulating TSH, particularly in the female sex [60]. Although autoimmunity may partially influence the relationship between TSH and BMI in humans [54,61], only few studies, and with conflicting results, have investigated the existence of thyroid autoimmunity in patients with obesity. In this regard, since the thyroid ultrasound scan in patients with obesity shows a hypoechoic pattern that could not be attributed to AITD, Rotondi et al. suggested [62] that ultrasound is not a diagnostic tool in these patients, unlike in the general population [36,63], and only the evaluation of antithyroid autoantibodies (ATAs) would be diagnostic for autoimmune thyroid disease (AITD) in obesity. It is remarkable that most of the studies investigating the relationship between TSH serum levels and obesity reported low numbers of ATAs positive patients, thus limiting the statistical power. Therefore, it is reasonable to assume that the contrasting results concerning the relationship between high normal TSH serum concentrations and obesity may partly depend on the different prevalence rates of underlying autoimmune thyroid diseases in the different studies. Moreover, these studies did not consider the TSH-BMI relationship on the basis of ATAs positivity [33,34,36,64,65]. Recently, in the Tehran Thyroid Study, Mahdavi et al. found an increased prevalence of TPOAb in a wide number of patients with obesity, explaining this association as a possible result of the obesity-related inflammatory and immune alterations in the thyroid gland of these patients [66]. The island of Sardinia presents a high prevalence of several autoimmune diseases [67,68,69,70,71,72,73], as well as a growing prevalence of obesity [74]. For these reasons, a study on Sardinian patients with obesity could reach a sufficient statistical strength to highlight any correlation between thyroid autoimmunity, anthropometric data, and high normal TSH levels. Based on this background, this study aimed to elucidate the role of thyroid autoimmunity in the relationship between thyroid and obesity in Sardinian euthyroid patients affected by overweight or obesity.

2. Materials and Methods

2.1. Experimental Sample Size

The study sample was retrospectively selected from a population of 1393 outpatients with overweight or obesity consecutively referred to the Obesity Unit of the University Hospital of Cagliari during the years 2015–2018.
Exclusion criteria were the following:
(a)
Overt or subclinical hyper/hypothyroidism and/or current or previous specific treatment for thyroid diseases (medical, surgical, radiometabolic) (236 patients);
Hyperthyroidism and hypothyroidism were diagnosed according to the current guidelines. Specifically, overt hyperthyroidism was defined by high serum fT4 or fT3 concentration and undetectable serum TSH concentration, while overt hypothyroidism was defined as low serum fT4 concentration, with elevated serum TSH concentration; subclinical hyperthyroidism was defined as serum TSH concentration below the lower limit of the reference range, with fT4 and fT3 concentration within their reference ranges, while subclinical hypothyroidism was defined as serum TSH concentration above the upper limit of the reference range, with fT4 concentration within its reference range [75,76,77].
(b)
History of intake of medications potentially affecting TSH levels (32 patients);
(c)
Diabetes mellitus (223 patients).
The study subjects were 902 euthyroid patients (213 males). ATAs were evaluated in 752 of them (186 males).

2.2. Anthropometric Data

The anthropometric evaluation was performed by an expert nutritionist as follows:
(a)
Height (expressed in cm), measured without shoes, with the participant’s head being in the “Frankfort plane”, by means of a stadiometer (SECA);
(b)
Body weight (expressed in kg), measured by wearing light clothes, by means of a mechanical scale (SECA 700);
(c)
BMI (Body Mass Index, expressed in kg/m2), calculated by the ratio of weight in kilograms and height in meters squared;
(d)
Waist circumference (WC) (expressed in cm), measured using recommendations of the Airlie conference (according to WHO criteria), considering as cut-off the International Diabetes Federation (IDF) values (94 cm for men and 80 cm for women) [78].

2.3. Blood Sampling and Analytes Measurements

Fasting venous blood samples were taken between 08:00 and 09:00 a.m. from the antecubital vein of the arm.
(a)
TSH was analyzed via an ultra-sensitive automatic chemiluminescence method (Ortho-Clinical Diagnostic SpA, Milan, Italy). The sensitivity was 0.004 µUI/L, and normal values were 0.4–4.1 µUI/L.
(b)
ATAs (thyroid peroxidase autoantibodies, TPOAb) were measured with a chemiluminescent method (Immulite 2000’s; Diagnostic Products Corporation, Los Angeles, CA, USA; Distributor Medical Systems Corporation, Genoa, Italy), and normal range values were 10–35 IU/mL.

2.4. Ethical Committee

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (AOU Cagliari, Prot.PG/2020/10920).

2.5. Statistical Analysis

The results for quantitative variables were expressed as mean value and standard deviation or median and range, based on the distribution of the data. The Kolmogorov–Smirnov (K-S) test showed a non-parametric distribution for TSH serum levels and a parametric distribution for both BMI and WC values. In this sense, TSH values were reported as median (range), and both BMI and WC values were reported as mean ± standard deviation (M ± SD).
Data were analyzed by using a non-parametric Kruskal-Wallis test for unpaired data, and the relationship between the quantitative variables was evaluated using the Spearman correlation test. For all the tests, a p-value (p) < 0.05 was considered as the limit of significance. All analyses were performed with SPSS version 25.0.

3. Results

All patients were aged between 18 and 79 years (M ± SD: 45.0 ± 14.2 years).
Based on BMI values, according to WHO criteria [3], 154 patients (24 males) with an average age of 40.3 years (SD ±13.7) were categorized as being overweight, 290 (70 males) as class I obesity (average age of 45.1 ± 14.3 years), 259 (58 males) as class II obesity (average age of 46.4 ± 14.3 years), and 199 (61 males) as class III obesity (average age of 46.7 ± 13.6). The mean BMI value of the whole sample was 35.8 ± 6.5 kg/m2.
In addition, the majority of patients presented WC values above the IDF cut-off: in fact, only seven patients (0.8% of the whole sample, one male) were within the established limits.
Table 1 shows the median values and range of TSH serum concentrations by BMI class: TSH levels were comparable between the four BMI groups (p = 0.302).
The patients were then grouped according to the ATAs’ positivity or negativity: positivity was found in 236 (26%) patients (44 males) with an average age of 44.6 ± 14.1 years. Negativity was found in 516 (57%) patients (142 males) with an average age of 44.2 ± 14.2 years. As shown in Table 2, the statistical comparison did not show any difference in TSH, BMI, or WC values between the two groups.
Dividing patients by sex, a slight increase in TSH, BMI, and WC values, although not significant, was observed only in ATAs-positive female patients (N = 191), as shown in Table 3.
Next, we considered the relationship between TSH values and BMI or WC values in terms of the correlation between TSH and the two anthropometric variables in the whole sample, stratified by sex and based on ATAs positivity.
Regarding the BMI, no significant results were obtained in the total sample and in the sample stratified by sex (in total sample: Spearman rho: −0.014; p: 0.682; in females: Spearman rho: 0.013; p: 0.730; in males: Spearman rho: −0.030; p: 0.666). Similarly, no significant results were found when considering only the ATAs-positive patients (N = 236: Spearman rho: −0.099; p: 0.130). However, when restricting the analysis to ATAs-positive females (N = 191), a positive correlation between TSH and BMI was observed (Spearman rho: 0.149; p: 0.040), as shown in Figure 1.
When considering the WC, no correlation with TSH was found across the whole sample (Spearman rho: −0.013; p: 0.703) and stratified by sex (in females: Spearman rho: 0.040; p: 0.309; in males: Spearman rho: −0.065; p: 0.358). Concerning ATAs status, the correlation was not significant in ATAs-positive patients of both sexes (N = 236, Spearman rho: 0.056; p: 0.401), and, in contrast with the findings on BMI, the correlation between WC and TSH was not significant when restricting the analysis to ATAs-positive females (N = 191, Spearman rho: 0.131; p: 0.075).

4. Discussion

In this study, we found a significant correlation between TSH within the reference range and BMI in ATAs (TPOAb)-positive female patients, despite the range restriction of TSH values possibly decreasing the Spearman’s rho value, which is reported to be lower when the variability between the observed values is small [79]. Therefore, the weakness of the correlation between TSH and BMI observed in our study in ATAs-positive euthyroid female patients could be explained by the restricted range of TSH values in our study population, as suggested by Bland, Altman et al. [80]. The positive association between TSH and BMI in subjects with thyroid autoimmunity is partially supported by the observations derived from population studies, in which the inclusion of ATAs-positive subjects shifted the Gaussian distribution of mean TSH values to the right [81,82]. Moreover, the higher prevalence of thyroid autoimmunity among women is widely reported [83]. In addition, our results are supported by some epidemiological surveys. Kitahara et al. [65] observed a positive correlation between serum TSH concentrations and BMI values among 3114 American adults, but when the 325 ATAs-positive patients were excluded, this result was not confirmed. Chen et al. [42] observed a significantly higher BMI mean value in ATAs-positive women compared with ATAs-negative women in 9082 adult subjects with normal TSH serum concentrations. Furthermore, this study showed that euthyroid AITD patients might have an increased cardiometabolic risk with respect to that associated with obesity per se. Additionally, a clinical study performed in a Spanish endocrine clinic by Diez et al. [64] found a positive correlation between serum TSH levels and BMI in 412 euthyroid obese patients, but this result was not confirmed when the 46 ATAs-positive patients were excluded. This finding is in line with our hypothesis, even if it is surprising that such a low number of ATAs-positive patients (10%), reported by Diez et al., was able to affect the relationship between TSH and BMI. Unlike the BMI, in our study, the waist circumference, a good marker of metabolic risk [84], was not significantly correlated with TSH values, even in ATAs-positive females, although a trend was observed. On this issue, our findings are only partially in line with the results of De Pergola et al. in euthyroid obese female patients [32] and with data reported in some studies on the general population [85,86], in which a correlation between WC and thyroid function was found exclusively in female subjects. However, in these studies, thyroid autoimmunity (ATAs) was not evaluated [32,85] or not considered relevant [86,87].
On the other hand, other studies on Asiatic people did not find any correlation between WC and TSH [88,89].
The main results of the studies mentioned above are summarized in Table 4.
It should be pointed out that in our study, the great majority of patients showed WC values above the cut-off, and the scarcity of values within the reference limits may have affected these results. Our findings could be explained by the hypothesis that obesity itself can play a role in autoimmunity [55,58,90,91], in particular through the action of leptin [92], and that high normal values of TSH may be linked to pro-inflammatory status and autoimmune activation [93]. Despite this possible and not-yet-established causal link, only a few and conflicting studies have investigated the causal role of thyroid autoimmunity on the high normal serum TSH concentrations in patients with obesity [33,35]. In a recent population-based study on more than 12,000 Chinese adults, overweight and obesity were associated with hyperthyrotropinemia exclusively in the presence of thyroid autoimmunity. Based on this result, the authors hypothesized that obesity could worsen the role of autoimmunity on hyperthyrotropinemia [94]. Our results are somewhat consistent with those of the aforementioned study, namely, the detection of higher, although within the normal range, TSH levels in ATAs-positive females. In addition, as expected by our previous studies on a Sardinian population [68,70], we found a higher prevalence (26%) of ATAs positivity in our series compared to the general European population [95,96]. This finding could be considered an important tool in the clinical evaluation of patients with overweight or obesity. In fact, even when TSH values are within the normal range, ATAs determination may be useful to identify patients suffering from AITD. Moreover, in these patients, the possible aggravating role of obesity in the pathogenesis of AITD requires particularly accurate treatment and monitoring of the weight excess. On the other hand, in ATAs-negative patients, the weight reduction could be sufficient to bring TSH values into the optimum range. However, a limitation of the cross-sectional studies is the inability to establish the potentially worsening effect of obesity on the development of thyroid dysfunction in ATAs-positive patients. In fact, only an observational study comparing a sample of obese patients with a sample of normal-weight subjects, both with ATAs positivity, could establish the role of obesity in worsening the progression toward thyroid failure. In the general population, the risk of developing hypothyroidism in women is 4.3% per year in those with raised TSH serum levels and ATAs positivity, 2.6% per year in those with raised TSH alone, and 2.1% per year in those with ATAs positivity alone, but the “weight of the weight” has not been considered [97]. Moreover, a further limitation is the exclusiveness and particularity of the ethnic group we studied, as it is not certain that the influence of autoimmunity is so decisive in other populations. Another possible limitation of our study could be the lack of measurement of free thyroid hormone levels. Nonetheless, only central hypothyroidism, which is rather uncommon, might be missed with a screening of the thyroid function based on TSH evaluation [95]. In addition, the behavior of serum thyroid hormone concentrations has shown a considerable variability in patients with obesity as a result of changes in nutritional habits [98], and in obese patients undergoing bariatric surgery, with the exception of patients affected by AITD [99].

5. Conclusions

In conclusion, this study suggests that in obese women with ATAs positivity, the high normal levels of TSH could be attributed to a mild thyroid failure, with a possible worsening obesity-related effect, while in all other cases, obesity per se could play a causal role.

Author Contributions

Conceptualization, F.V. and A.L.; methodology, S.P. and G.S. (Gianni Secci); validation, G.F., A.P.D. and F.B.; formal analysis, M.G.; investigation, G.S. (Gianmarco Sainas), R.R., F.B., A.P.D., G.F. and A.D.; survey, G.S. (Gianni Secci); resources, A.L.; data curation, R.R.; writing—original draft preparation, A.L. and S.P.; writing—review and editing, F.V., M.F., G.S. (Gianni Secci) and A.D.; visualization, M.F. and A.D.; supervision, F.V. and A.L.; project administration, A.L.; acquisition of funding, A.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of AOU Cagliari (Prot.PG/2020/10920).

Informed Consent Statement

The Ethical Committee authorized the use of the data without the patient consent due the inability to contact the patients (subjects identified by a code; contact data not available in the file of data).

Data Availability Statement

The datasets used and/or analysed during the current study will be made available by the authors on reasonable request.

Acknowledgments

The authors would like to thank Stefano Mariotti for his contribution to the study design and Lorenzo Loviselli for his support in the English editing of the manuscript.

Conflicts of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Ward, Z.J.; Willett, W.C.; Hu, F.B.; Pacheco, L.S.; Long, M.W.; Gortmaker, S.L. Excess mortality associated with elevated body weight in the USA by state and demographic subgroup: A modelling study. EClinicalMedicine 2022, 48, 101429. [Google Scholar] [CrossRef] [PubMed]
  2. Inoue, Y.; Qin, B.; Poti, J.; Sokol, R.; Gordon-Larsen, P. Epidemiology of Obesity in Adults: Latest Trends. Curr. Obes. Rep. 2018, 7, 276–288. [Google Scholar] [CrossRef]
  3. World Health Organisation. Obesity and Overweight—Key Facts. 2018. Available online: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed on 26 November 2018).
  4. Chaker, L.; Bianco, A.C.; Jonklaas, J.; Peeters, R.P. Hypothyroidism. Lancet 2017, 390, 1550–1562. [Google Scholar] [CrossRef]
  5. Biondi, B.; Cappola, A.R.; Cooper, D.S. Subclinical Hypothyroidism. JAMA 2019, 322, 153–160. [Google Scholar] [CrossRef] [PubMed]
  6. Taylor, P.N.; Albrecht, D.; Scholz, A.; Gutierrez-Buey, G.; Lazarus, J.H.; Dayan, C.M.; Okosieme, O.E. Global epidemiology of hyperthyroidism and hypothyroidism. Nat. Rev. Endocrinol. 2018, 14, 301–316. [Google Scholar] [CrossRef] [PubMed]
  7. Canaris, G.J.; Manowitz, N.R.; Mayor, G.; Ridgway, E.C. The Colorado Thyroid Disease Prevalence Study. Arch. Intern. Med. 2000, 160, 526–534. [Google Scholar] [CrossRef] [PubMed]
  8. Ro, K.; Yuen, A.D.; Du, L.; Ro, C.C.; Seger, C.; Yeh, M.W.; Leung, A.M.; Rhee, C.M. Impact of Hypothyroidism and Heart Failure on Hospitalization Risk. Thyroid 2018, 28, 1094–1100. [Google Scholar] [CrossRef]
  9. Bano, A.; Chaker, L.; Mattace-Raso, F.U.S.; Terzikhan, N.; Kavousi, M.; Ikram, M.A.; Peeters, R.P.; Franco, O.H. Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study. PLoS Med. 2019, 16, e1002957. [Google Scholar] [CrossRef]
  10. GBD 2015 Obesity Collaborators; Afshin, A.; Forouzanfar, M.H.; Reitsma, M.B.; Sur, P.; Estep, K.; Lee, A.; Marczak, L.; Mokdad, A.H.; Moradi-Lakeh, M.; et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med. 2017, 377, 13–27. [Google Scholar] [CrossRef]
  11. Biondi, B. Thyroid and Obesity: An Intriguing Relationship. J. Clin. Endocrinol. Metab. 2010, 95, 3614–3617. [Google Scholar] [CrossRef] [Green Version]
  12. Pasquali, R.; Casanueva, F.; Haluzik, M.; Van Hulsteijn, L.; LeDoux, S.; Monteiro, M.; Salvador, J.; Santini, F.; Toplak, H.; Dekkers, O.M. European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity. Eur. J. Endocrinol. 2020, 182, G1–G32. [Google Scholar] [CrossRef] [PubMed]
  13. Valdés, S.; Maldonado-Araque, C.; Lago-Sampedro, A.M.; Lillo-Muñoz, J.A.; Garcia-Fuentes, E.; Perez-Valero, V.; Gutiérrez-Repiso, C.; Garcia-Escobar, E.; Goday, A.; Urrutia, I.; et al. Reference values for TSH may be inadequate to define hypothyroidism in persons with morbid obesity: [email protected] study. Obesity 2017, 25, 788–793. [Google Scholar] [CrossRef]
  14. Knudsen, N.; Laurberg, P.; Rasmussen, L.B.; Bülow, I.; Perrild, H.; Ovesen, L.; Jørgensen, T. Small Differences in Thyroid Function May Be Important for Body Mass Index and the Occurrence of Obesity in the Population. J. Clin. Endocrinol. Metab. 2005, 90, 4019–4024. [Google Scholar] [CrossRef] [PubMed]
  15. Åsvold, B.O.; Bjøro, T.; Vatten, L.J. Association of Serum TSH with High Body Mass Differs between Smokers and Never-Smokers. J. Clin. Endocrinol. Metab. 2009, 94, 5023–5027. [Google Scholar] [CrossRef]
  16. Dvořáková, M.; Hill, M.; Čeřovská, J.; Pobišová, Z.; Bílek, R.; Hoskovcová, P.; Zamrazil, V.; Hainer, V. Relationship between Pituitary-Thyroid Axis Hormones and Anthropometric Parameters in Czech Adult Population. Physiol. Res. 2008, 57, S127–S134. [Google Scholar] [CrossRef] [PubMed]
  17. Fox, C.S.; Pencina, M.J.; D’Agostino, R.B.; Murabito, J.; Seely, E.W.; Pearce, E.N.; Vasan, R.S. Relations of Thyroid Function to Body WeightCross-sectional and Longitudinal Observations in a Community-Based Sample. Arch. Intern. Med. 2008, 168, 587–592. [Google Scholar] [CrossRef] [PubMed]
  18. Gopinath, B.; Liew, G.; Flood, V.M.; Wang, J.J.; Kifley, A.; Leeder, S.R.; Mitchell, P. The Association Between Weight Gain and Thyroid Function in an Older Population. Arch. Intern. Med. 2008, 168, 2283–2284. [Google Scholar] [CrossRef]
  19. Nyrnes, A.; Jorde, R.; Sundsfjord, J. Serum TSH is positively associated with BMI. Int. J. Obes. 2005, 30, 100–105. [Google Scholar] [CrossRef]
  20. Svare, A.; Nilsen, T.I.L.; Bjøro, T.; Åsvold, B.O.; Langhammer, A. Serum TSH related to measures of body mass: Longitudinal data from the HUNT Study, Norway. Clin. Endocrinol. 2011, 74, 769–775. [Google Scholar] [CrossRef]
  21. Ambrosi, B.; Masserini, B.; Iorio, L.; Delnevo, A.; Malavazos, A.E.; Morricone, L.; Sburlati, L.F.; Orsi, E. Relationship of thyroid function with body mass index and insulin-resistance in euthyroid obese subjects. J. Endocrinol. Investig. 2010, 33, 640–643. [Google Scholar] [CrossRef]
  22. Bastemir, M.; Akin, F.; Alkis, E.; Kaptanoglu, E.B. Obesity is associated with increased serum TSH level, independent of thy-roid function. Swiss Med. Wkly. 2007, 137, 431–434. [Google Scholar] [PubMed]
  23. Bétry, C.; Challan-Belval, M.; Bernard, A.; Charrié, A.; Drai, J.; Laville, M.; Thivolet, C.; Disse, E. Increased TSH in obesity: Evidence for a BMI-independent association with leptin. Diabetes Metab. 2014, 41, 248–251. [Google Scholar] [CrossRef]
  24. Chikunguwo, S.; Brethauer, S.; Nirujogi, V.; Pitt, T.; Udomsawaengsup, S.; Chand, B.; Schauer, P. Influence of obesity and surgical weight loss on thyroid hormone levels. Surg. Obes. Relat. Dis. 2007, 3, 631–635. [Google Scholar] [CrossRef] [PubMed]
  25. Galofré, J.C.; Pujante, P.; Abreu, C.; Santos, S.; Guillen-Grima, F.; Frühbeck, G.; Salvador, J. Relationship between Thyroid-Stimulating Hormone and Insulin in Euthyroid Obese Men. Ann. Nutr. Metab. 2008, 53, 188–194. [Google Scholar] [CrossRef]
  26. Iacobellis, G.; Ribaudo, M.C.; Zappaterreno, A.; Iannucci, C.V.; Leonetti, F. Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women. Clin. Endocrinol. 2005, 62, 487–491. [Google Scholar] [CrossRef] [PubMed]
  27. Kouidhi, S.; Berhouma, R.; Ammar, M.; Rouissi, K.; Jarboui, S.; Clerget-Froidevaux, M.-S.; Seugnet, I.; Abid, H.; Bchir, F.; Demeneix, B.; et al. Relationship of Thyroid Function with Obesity and Type 2 Diabetes in Euthyroid Tunisian Subjects. Endocr. Res. 2012, 38, 15–23. [Google Scholar] [CrossRef] [PubMed]
  28. Choi, S.H.; Lee, Y.J.; Park, Y.J.; Kim, K.W.; Lee, E.J.; Lim, S.; Park, D.J.; Kim, S.E.; Park, K.S.; Jang, H.C.; et al. Retinol Binding Protein-4 Elevation Is Associated with Serum Thyroid-Stimulating Hormone Level Independently of Obesity in Elderly Subjects with Normal Glucose Tolerance. J. Clin. Endocrinol. Metab. 2008, 93, 2313–2318. [Google Scholar] [CrossRef]
  29. Makepeace, A.E.; Bremner, A.; O’Leary, P.; Leedman, P.J.; Feddema, P.; Michelangeli, V.; Walsh, J.P. Significant inverse relationship between serum free T4 concentration and body mass index in euthyroid subjects: Differences between smokers and nonsmokers. Clin. Endocrinol. 2008, 69, 648–652. [Google Scholar] [CrossRef]
  30. Shon, H.S.; Jung, E.D.; Kim, S.H.; Lee, J.H. Free T4 is negatively correlated with body mass index in euthyroid women. Korean J. Intern. Med. 2008, 23, 53–57. [Google Scholar] [CrossRef]
  31. Bakiner, O.; Bozkirli, E.; Cavlak, G.; Ozsahin, K.; Ertorer, E. Are Plasma Thyroid-Stimulating Hormone Levels Associated with Degree of Obesity and Metabolic Syndrome in Euthyroid Obese Patients? A Turkish Cohort Study. ISRN Endocrinol. 2014, 2014, 803028. [Google Scholar] [CrossRef] [Green Version]
  32. De Pergola, G.; Ciampolillo, A.; Paolotti, S.; Trerotoli, P.; Giorgino, R. Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women. Clin. Endocrinol. 2007, 67, 265–269. [Google Scholar] [CrossRef] [PubMed]
  33. Manji, N.; Boelaert, K.; Sheppard, M.C.; Holder, R.L.; Gough, S.C.; Franklyn, J.A. Lack of association between serum TSH or free T4 and body mass index in euthyroid subjects. Clin. Endocrinol. 2006, 64, 125–128. [Google Scholar] [CrossRef] [PubMed]
  34. Michalaki, M.A.; Vagenakis, A.G.; Leonardou, A.S.; Argentou, M.N.; Habeos, I.G.; Makri, M.G.; Psyrogiannis, A.I.; Kalfarentzos, F.E.; Kyriazopoulou, V.E. Thyroid Function in Humans with Morbid Obesity. Thyroid 2006, 16, 73–78. [Google Scholar] [CrossRef] [PubMed]
  35. Muscogiuri, G.; Sorice, G.P.; Mezza, T.; Prioletta, A.; Lassandro, A.P.; Pirronti, T.; Della Casa, S.; Pontecorvi, A.; Giaccari, A. High-normal tsh values in obesity: Is it insulin resistance or adipose tissue’s guilt? Obesity 2013, 21, 101–106. [Google Scholar] [CrossRef] [PubMed]
  36. Rotondi, M.; Leporati, P.; La Manna, A.; Pirali, B.; Mondello, T.; Fonte, R.; Magri, F.; Chiovato, L. Raised serum TSH levels in patients with morbid obesity: Is it enough to diagnose subclinical hypothyroidism? Eur. J. Endocrinol. 2009, 160, 403–408. [Google Scholar] [CrossRef] [PubMed]
  37. Fontenelle, L.C.; Feitosa, M.M.; Severo, J.S.; Freitas, T.E.C.; Morais, J.B.S.; Torres-Leal, F.L.; Henriques, G.S.; Marreiro, D.D.N. Thyroid Function in Human Obesity: Underlying Mechanisms. Horm. Metab. Res. 2016, 48, 787–794. [Google Scholar] [CrossRef]
  38. Bjergved, L.; Jørgensen, T.; Perrild, H.; Laurberg, P.; Krejbjerg, A.; Ovesen, L.; Rasmussen, L.B.; Knudsen, N. Thyroid Function and Body Weight: A Community-Based Longitudinal Study. PLoS ONE 2014, 9, e93515. [Google Scholar] [CrossRef]
  39. Juiz-Valiña, P.; Outeiriño-Blanco, E.; Pértega, S.; Varela-Rodríguez, B.M.; García-Brao, M.J.; Mena, E.; Pena-Bello, L.; Cordido, M.; Sangiao-Alvarellos, S.; Cordido, F. Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Euthyroid Patients with Morbid Obesity. Nutrients 2019, 11, 1121. [Google Scholar] [CrossRef]
  40. Juiz-Valiña, P.; Cordido, M.; Outeiriño-Blanco, E.; Pértega, S.; Varela-Rodríguez, B.M.; García-Brao, M.J.; Mena, E.; Pena-Bello, L.; Sangiao-Alvarellos, S.; Cordido, F. Central Resistance to Thyroid Hormones in Morbidly Obese Subjects Is Reversed after Bariatric Surgery-Induced Weight Loss. J. Clin. Med. 2020, 9, 359. [Google Scholar] [CrossRef]
  41. Cordido, M.; Juiz-Valiña, P.; Urones, P.; Sangiao-Alvarellos, S.; Cordido, F. Thyroid Function Alteration in Obesity and the Effect of Bariatric Surgery. J. Clin. Med. 2022, 11, 1340. [Google Scholar] [CrossRef]
  42. Chen, Y.; Zhu, C.; Chen, Y.; Wang, N.; Li, Q.; Han, B.; Zhao, L.; Chen, C.; Zhai, H.; Zhang, L.; et al. Are Thyroid Autoimmune Diseases Associated with Cardiometabolic Risks in a Population with Normal Thyroid-Stimulating Hormone? Mediat. Inflamm. 2018, 2018, 1856137. [Google Scholar] [CrossRef]
  43. Jurado-Flores, M.; Warda, F.; Mooradian, A. Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease. J. Endocr. Soc. 2022, 6, bvab194. [Google Scholar] [CrossRef] [PubMed]
  44. Pinna, F.; Sardu, C.; Orrù, W.; Velluzzi, F.; Loviselli, A.; Contu, P.; Carpiniello, B. Psychopathology, psychosocial factors and obesity. Riv. Psichiatr. 2016, 51, 30–36. [Google Scholar] [CrossRef] [PubMed]
  45. Marzullo, P.; Minocci, A.; Mele, C.; Fessehatsion, R.; Tagliaferri, M.; Pagano, L.; Scacchi, M.; Aimaretti, G.; Sartorio, A. The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity. PLoS ONE 2018, 13, e0205293. [Google Scholar] [CrossRef] [PubMed]
  46. Kaptein, E.M.; Beale, E.; Chan, L.S. Thyroid Hormone Therapy for Obesity and Nonthyroidal Illnesses: A Systematic Review. J. Clin. Endocrinol. Metab. 2009, 94, 3663–3675. [Google Scholar] [CrossRef]
  47. Deledda, A.; Annunziata, G.; Tenore, G.; Palmas, V.; Manzin, A.; Velluzzi, F. Diet-Derived Antioxidants and Their Role in Inflammation, Obesity and Gut Microbiota Modulation. Antioxidants 2021, 10, 708. [Google Scholar] [CrossRef]
  48. Gregor, M.F.; Hotamisligil, G.S. Inflammatory Mechanisms in Obesity. Annu. Rev. Immunol. 2011, 29, 415–445. [Google Scholar] [CrossRef]
  49. Hotamisligil, G.S. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int. J. Obes. 2008, 32, S52–S54. [Google Scholar] [CrossRef]
  50. Taddei, S.; Ghiadoni, L.; Salvetti, G.; Virdis, A.; Salvetti, A. Obesity and endothelial dysfunction. G Ital. Cardiol. 2006, 7, 715–723. [Google Scholar]
  51. Gómez-Zamudio, J.H.; Mendoza-Zubieta, V.; Ferreira-Hermosillo, A.; Molina-Ayala, M.A.; Valladares-Sálgado, A.; Suárez-Sánchez, F.; Peralta-Romero, J.D.J.; Cruz, M. High Thyroid-stimulating Hormone Levels Increase Proinflammatory and Cardiovascular Markers in Patients with Extreme Obesity. Arch. Med. Res. 2016, 47, 476–482. [Google Scholar] [CrossRef]
  52. Kvetny, J.; Heldgaard, P.E.; Bladbjerg, E.M.; Gram, J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin. Endocrinol. 2004, 61, 232–238. [Google Scholar] [CrossRef] [PubMed]
  53. Taddei, S.; Caraccio, N.; Virdis, A.; Dardano, A.; Versari, D.; Ghiadoni, L.; Ferrannini, E.; Salvetti, A.; Monzani, F. Low-Grade Systemic Inflammation Causes Endothelial Dysfunction in Patients with Hashimoto’s Thyroiditis. J. Clin. Endocrinol. Metab. 2006, 91, 5076–5082. [Google Scholar] [CrossRef] [PubMed]
  54. Duntas, L.H.; Biondi, B. The Interconnections Between Obesity, Thyroid Function, and Autoimmunity: The Multifold Role of Leptin. Thyroid 2013, 23, 646–653. [Google Scholar] [CrossRef] [PubMed]
  55. A Exley, M.; Hand, L.; O’Shea, D.; Lynch, L. Interplay between the immune system and adipose tissue in obesity. J. Endocrinol. 2014, 223, R41–R48. [Google Scholar] [CrossRef]
  56. Gerriets, V.A.; Danzaki, K.; Kishton, R.J.; Eisner, W.; Nichols, A.G.; Saucillo, D.C.; Shinohara, M.L.; MacIver, N.J. Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity. Eur. J. Immunol. 2016, 46, 1970–1983. [Google Scholar] [CrossRef]
  57. Harpsøe, M.C.; Basit, S.; Andersson, M.; Nielsen, N.M.; Frisch, M.; Wohlfahrt, J.; A Nohr, E.; Linneberg, A.; Jess, T. Body mass index and risk of autoimmune diseases: A study within the Danish National Birth Cohort. Int. J. Epidemiology 2014, 43, 843–855. [Google Scholar] [CrossRef]
  58. Versini, M.; Jeandel, P.-Y.; Rosenthal, E.; Shoenfeld, Y. Obesity in autoimmune diseases: Not a passive bystander. Autoimmun. Rev. 2014, 13, 981–1000. [Google Scholar] [CrossRef]
  59. Song, R.-H.; Wang, B.; Yao, Q.-M.; Li, Q.; Jia, X.; Zhang, J.-A. The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis. Front. Immunol. 2019, 10. [Google Scholar] [CrossRef]
  60. Altay, S.; Onat, A.; Can, G.; Tusun, E.; Şimşek, B.; Kaya, A. High-normal thyroid-stimulating hormone in euthyroid subjects is associated with risk of mortality and composite disease endpoint only in women. Arch. Med Sci. 2018, 14, 1394–1403. [Google Scholar] [CrossRef]
  61. Santini, F.; Marzullo, P.; Rotondi, M.; Ceccarini, G.; Pagano, L.; Ippolito, S.; Chiovato, L.; Biondi, B. MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: Signal integration in health and disease. Eur. J. Endocrinol. 2014, 171, R137–R152. [Google Scholar] [CrossRef]
  62. Rotondi, M.; Cappelli, C.; Leporati, P.; Chytiris, S.; Zerbini, F.; Fonte, R.; Magri, F.; Castellano, M.; Chiovato, L. A hypoechoic pattern of the thyroid at ultrasound does not indicate autoimmune thyroid diseases in patients with morbid obesity. Eur. J. Endocrinol. 2010, 163, 105–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Rago, T.; Chiovato, L.; Grasso, L.; Pinchera, A.; Vitti, P. Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dysfunction in apparently healthy subjects. J. Endocrinol. Investig. 2001, 24, 763–769. [Google Scholar] [CrossRef] [PubMed]
  64. Díez, J.J.; Iglesias, P. Relationship Between Thyrotropin and Body Mass Index in Euthyroid Subjects. Exp. Clin. Endocrinol. Diabetes 2010, 119, 144–150. [Google Scholar] [CrossRef] [PubMed]
  65. Kitahara, C.M.; Platz, E.A.; Ladenson, P.W.; Mondul, A.M.; Menke, A.; De González, A.B. Body Fatness and Markers of Thyroid Function among U.S. Men and Women. PLoS ONE 2012, 7, e34979. [Google Scholar] [CrossRef]
  66. Mahdavi, M.; Amouzegar, A.; Mehran, L.; Madreseh, E.; Tohidi, M.; Azizi, F. Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study. BMC Endocr. Disord. 2021, 21, 89. [Google Scholar] [CrossRef]
  67. Bocchetta, A.; Ambrosiani, L.; Baggiani, G.; Pisanu, C.; Chillotti, C.; Ardau, R.; Velluzzi, F.; Piras, D.; Loviselli, A.; Pani, A. Circulating antithyroid antibodies contribute to the decrease of glomerular filtration rate in lithium-treated patients: A longitudinal study. Int. J. Bipolar Disord. 2018, 6, 3. [Google Scholar] [CrossRef]
  68. Delitala, A.P.; Pilia, M.G.; Ferreli, L.; Loi, F.; Curreli, N.; Balaci, L.; Schlessinger, D.; Cucca, F. Prevalence of unknown thyroid disorders in a Sardinian cohort. Eur. J. Endocrinol. 2014, 171, 143–149. [Google Scholar] [CrossRef]
  69. Lampis, R.; Morelli, L.; Congia, M.; Macis, M.D.; Mulargia, A.; Loddo, M.; De Virgiliis, S.; Marrosu, M.G.; Todd, J.A.; Cucca, F. The inter-regional distribution of HLA class II haplotypes indicates the suitability of the Sardinian population for case-control association studies in complex diseases. Hum. Mol. Genet. 2000, 9, 2959–2965. [Google Scholar] [CrossRef]
  70. Loviselli, A.; Velluzzi, F.; Mossa, P.; Cambosu, M.; Secci, G.; Atzeni, F.; Taberlet, A.; Balestrieri, A.; Martino, E.; Grasso, L.; et al. The Sardinian Autoimmunity Study: 3. Studies on Circulating Antithyroid Antibodies in Sardinian Schoolchildren: Relationship to Goiter Prevalence and Thyroid Function. Thyroid 2001, 11, 849–857. [Google Scholar] [CrossRef]
  71. Sardu, C.; Cocco, E.; Mereu, A.; Massa, R.; Cuccu, A.; Marrosu, M.G.; Contu, P. Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity. PLoS ONE 2012, 7, e32487. [Google Scholar] [CrossRef]
  72. Songini, M.; Loche, M.; Muntoni, S.; Stabilini, M.; Coppola, A.; Dessi, G.; Green, A.; Bottazzo, G.F. Increasing prevalence of juvenile onset Type 1 (insulin-dependent) diabetes mellitus in Sardinia: The military service approach. Diabetologia 1993, 36, 547–552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Velluzzi, F.; The Sardinian Autoimmunity Study Group; Secci, G.; Sepe, V.; Klersy, C.; Shattock, M.; Foxon, R.; Songini, M.; Mariotti, S.; Locatelli, M.; et al. Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study. Geol. Rundsch. 2015, 53, 73–79. [Google Scholar] [CrossRef] [PubMed]
  74. Loviselli, A.; Ghiani, M.E.; Velluzzi, F.; Piras, I.S.; Minerba, L.; Vona, G.; Calò, C.M. Prevalence and Trend of Overweight and Obesity among Sardinian Conscripts (Italy) of 1969 and 1998. J. Biosoc. Sci. 2009, 42, 201–211. [Google Scholar] [CrossRef]
  75. Surks, M.I.; Ortiz, E.; Daniels, G.H.; Sawin, C.T.; Col, N.F.; Cobin, R.H.; Franklyn, J.A.; Hershman, J.M.; Burman, K.D.; Denke, M.A.; et al. Subclinical Thyroid Disease. JAMA 2004, 291, 228–238. [Google Scholar] [CrossRef] [PubMed]
  76. Surks, M.I.; Chopra, I.J.; Mariash, C.N.; Nicoloff, J.T.; Solomon, E.D.H. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 1990, 263, 1529–1532. [Google Scholar] [CrossRef]
  77. E Croker, E.; A McGrath, S.; Rowe, C.W. Thyroid disease: Using diagnostic tools effectively. Aust. J. Gen. Pract. 2021, 50, 16–21. [Google Scholar] [CrossRef]
  78. WHO. Waist Circumference and Waist-Hip Ratio: Report of a WHO Expert Consultation, Geneva, 8–11 December 2008; World Health Organization: Geneva, Switzerland, 2011; 39p. [Google Scholar]
  79. Yarnold, P.R.; Bryant, F.B.; Soltysik, E.R.C. Maximizing the Accuracy of Multiple Regression Models using UniODA: Regression away from the Mean. Optim. Data Anal. 2013, 2, 19–25. [Google Scholar]
  80. Bland, J.M.; Altman, D.G. Correlation in restricted ranges of data. BMJ 2011, 342, d556. [Google Scholar] [CrossRef]
  81. Jonklaas, J.; Razvi, S. Reference intervals in the diagnosis of thyroid dysfunction: Treating patients not numbers. Lancet Diabetes Endocrinol. 2019, 7, 473–483. [Google Scholar] [CrossRef]
  82. Spencer, C.A.; Hollowell, J.G.; Kazarosyan, M.; Braverman, L. National Health and Nutrition Examination Survey III Thyroid-Stimulating Hormone (TSH)-Thyroperoxidase Antibody Relationships Demonstrate That TSH Upper Reference Limits May Be Skewed by Occult Thyroid Dysfunction. J. Clin. Endocrinol. Metab. 2007, 92, 4236–4240. [Google Scholar] [CrossRef]
  83. Chiovato, L.; Lapi, P.; Fiore, E.; Tonacchera, M.; Pinchera, A. Thyroid autoimmunity and female gender. J. Endocrinol. Investig. 1993, 16, 384–391. [Google Scholar] [CrossRef] [PubMed]
  84. Iliodromiti, S.; Celis-Morales, C.A.; Lyall, D.M.; Anderson, J.; Gray, S.R.; Mackay, D.F.; Nelson, S.M.; Welsh, P.; Pell, J.P.; Gill, J.M.R.; et al. The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: A cohort study of 296 535 adults of white European descent. Eur. Heart J. 2018, 39, 1514–1520. [Google Scholar] [CrossRef] [PubMed]
  85. Delitala, A.P.; Scuteri, A.; Fiorillo, E.; Lakatta, E.G.; Schlessinger, D.; Cucca, F. Role of Adipokines in the Association between Thyroid Hormone and Components of the Metabolic Syndrome. J. Clin. Med. 2019, 8, 764. [Google Scholar] [CrossRef]
  86. Diniz, M.D.F.H.S.; Beleigoli, A.; Benseñor, I.M.; Lotufo, P.A.; Goulart, A.C.; Barreto, S.M. Association between TSH levels within the reference range and adiposity markers at the baseline of the ELSA–Brasil study. PLoS ONE 2020, 15, e0228801. [Google Scholar] [CrossRef] [PubMed]
  87. Chen, Y.; Chen, Y.; Wang, N.; Chen, C.; Nie, X.; Li, Q.; Han, B.; Lu, Y. Thyroid Stimulating Hormone Within the Reference Range is Associated with Visceral Adiposity Index and Lipid Accumulation Product: A Population-Based Study of SPECT-China. Horm. Metab. Res. 2017, 50, 29–36. [Google Scholar] [CrossRef]
  88. Liu, X.; Zhang, C.; Meng, Z.; Li, X.; Liu, M.; Ren, X.; Zhu, M.; He, Q.; Zhang, Q.; Song, K.; et al. Waist Circumference and Subclinical Thyroid Dysfunction in a Large Cohort of Chinese Men and Women. Endocr. Pract. 2018, 24, 733–739. [Google Scholar] [CrossRef]
  89. Sakurai, M.; Nakamura, K.; Miura, K.; Yoshita, K.; Takamura, T.; Nagasawa, S.-Y.; Morikawa, Y.; Ishizaki, M.; Kido, T.; Naruse, Y.; et al. Association between a Serum Thyroid-stimulating Hormone Concentration within the Normal Range and Indices of Obesity in Japanese Men and Women. Intern. Med. 2014, 53, 669–674. [Google Scholar] [CrossRef]
  90. Lukens, J.R.; Dixit, V.D.; Kanneganti, E.T.-D. Inflammasome activation in obesity-related inflammatory diseases and auto-immunity. Discov. Med. 2011, 12, 65–74. [Google Scholar]
  91. Versini, M.; Aljadeff, G.; Jeandel, P.-Y.; Shoenfeld, Y. Obesity: An additional piece in the mosaic of autoimmunity. Isr. Med Assoc. J. IMAJ 2014, 16, 619–621. [Google Scholar]
  92. Loviselli, A.; Secci, G.; Lai, A.; Velluzzi, F. Mechanisms of regulation of the food intake: Recent advances. Recenti. Prog. Med. 2007, 98, 1–6. [Google Scholar]
  93. Onat, A.; Aydın, M.; Can, G.; Çelik, E.; Altay, S.; Karagöz, A.; Ademoğlu, E. Normal thyroid-stimulating hormone levels, autoimmune activation, and coronary heart disease risk. Endocrine 2014, 48, 218–226. [Google Scholar] [CrossRef] [PubMed]
  94. Guo, X.; He, Z.; Shao, S.; Fu, Y.; Zheng, D.; Liu, L.; Gao, L.; Guan, L.; Zhao, M.; Zhao, J. Interaction effect of obesity and thyroid autoimmunity on the prevalence of hyperthyrotropinaemia. Endocrine 2020, 68, 573–583. [Google Scholar] [CrossRef] [PubMed]
  95. Madariaga, A.G.; Palacios, S.S.; Guillen-Grima, F.; Galofré, J.C. The Incidence and Prevalence of Thyroid Dysfunction in Europe: A Meta-Analysis. J. Clin. Endocrinol. Metab. 2014, 99, 923–931. [Google Scholar] [CrossRef] [PubMed]
  96. McLeod, D.S.A.; Cooper, D.S. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012, 42, 252–265. [Google Scholar] [CrossRef] [PubMed]
  97. Vanderpump, M.P.J.; Tunbrldge, W.M.G.; French, J.M.; Appleton, D.; Bates, D.; Clark, F.; Evans, J.G.; Hasan, D.M.; Rodgers, H.; Tunbridge, F.; et al. The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clin. Endocrinol. 1995, 43, 55–68. [Google Scholar] [CrossRef]
  98. Pasquali, R.; Vicennati, V. The Abdominal Obesity Phenotype and Insulin Resistance are Associated with Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis in Humans. Horm. Metab. Res. 2000, 32, 521–525. [Google Scholar] [CrossRef]
  99. Guan, B.; Chen, Y.; Yang, J.; Yang, W.; Wang, C. Effect of Bariatric Surgery on Thyroid Function in Obese Patients: A Systematic Review and Meta-Analysis. Obes. Surg. 2017, 27, 3292–3305. [Google Scholar] [CrossRef] [PubMed]
Jcm 11 05125 g001 550
Figure 1. Spearman’s correlation between TSH and BMI in ATAs-positive female patients.
Figure 1. Spearman’s correlation between TSH and BMI in ATAs-positive female patients.
Jcm 11 05125 g001
Table
Table 1. Median values and range of TSH serum concentrations by BMI class.
Table 1. Median values and range of TSH serum concentrations by BMI class.
Class (BMI)NumberTSH (μUI/L)
Overweight (25.0–29.9)1541.9 (0.4–4.0)
Class I Obesity (30.0–34.9)2901.9 (0.5–4.1)
Class II Obesity (35.0–39.9)2591.8 (0.4–4.1)
Class III Obesity (≥40)1991.9 (0.5–4.1)
Abbreviations: BMI = Body Mass Index (kg/m2), TSH = Thyroid-Stimulating Hormone.
Table
Table 2. TSH serum levels, BMI, and WC values according to ATAs status in the whole sample.
Table 2. TSH serum levels, BMI, and WC values according to ATAs status in the whole sample.
ATAs+ Patients (N = 236)ATAs- Patients (N = 516)
VariableMedian (Range)M ± SDMedian (Range)M ± SDp-Value
TSH (μUI/L)1.85 (0.7–3.7) 1.86 (0.7–3.5) 0.504
BMI (kg/m2) 36.0 ± 6.8 35.8 ± 6.40.749
WC (cm) 112.4 ± 14 112.2 ± 14.20.907
Abbreviations: ATAs = Anti-Thyroid Autoantibodies (thyroid peroxidase autoantibodies), BMI = Body Mass Index, M = Mean, SD = Standard Deviation, TSH = Thyroid-Stimulating Hormone, WC = Waist Circumference.
Table
Table 3. TSH serum levels, BMI, and WC values according to ATAs’ status in female patients.
Table 3. TSH serum levels, BMI, and WC values according to ATAs’ status in female patients.
ATAs+ Patients (N = 191)ATAs- Patients (N = 375)
VariableMedian (Range)M ± SDMedian (Range)M ± SDp-Value
TSH (μUI/L)1.91 (0.7–3.7) 1.90 (0.8–3.6) 0.412
BMI (kg/m2) 36.0 ± 6.9 35.1 ± 6.10.241
WC (cm) 111 ± 14.1 109.5 ± 13.20.194
Abbreviations: ATAs = Anti-Thyroid Autoantibodies (thyroid peroxidase autoantibodies), BMI = Body Mass Index, M = Mean, SD= Standard Deviation, TSH = Thyroid-Stimulating Hormone, WC = Waist Circumference.
Table
Table 4. Association between anthropometric measures and TSH in euthyroid adults.
Table 4. Association between anthropometric measures and TSH in euthyroid adults.
AuthorPeople AssessedResults
Kitahara [66]—USA3.114 euthyroid adultsTSH positively associated with BMI only when ATAs-positive patients were considered
Chen [42]—Japan9.082 euthyroid adultsTSH positively associated with BMI in ATAs-positive women
Diez [65]—Spain412 euthyroid obese adults TSH positively associated with BMI only when ATAs-positive patients were considered
De Pergola [32]–Italy201 euthyroid women TSH positively associated with WC
Diniz [87]—Brazil11.224 euthyroid adultsTSH associated with BMI and WC only in women
Delitala [86]—Italy4.733 euthyroid adultsTSH not associated with anthropometric measures
Liu [89]—China13.505 euthyroid adultsTSH not associated with WC
Sakurai [90]—Japan2.037 euthyroid adultsTSH not associated with WC
Abbreviations: TSH = Thyroid-Stimulating Hormone, BMI = Body Mass Index (g/m2), ATAs = Anti-Thyroid Autoantibodies, WC = Waist Circumference.
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Velluzzi, F.; Pisanu, S.; Galletta, M.; Fosci, M.; Secci, G.; Deledda, A.; Boi, F.; Rodia, R.; Fanciulli, G.; Delitala, A.P.; et al. Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs). J. Clin. Med. 2022, 11, 5125. https://doi.org/10.3390/jcm11175125

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Velluzzi F, Pisanu S, Galletta M, Fosci M, Secci G, Deledda A, Boi F, Rodia R, Fanciulli G, Delitala AP, et al. Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs). Journal of Clinical Medicine. 2022; 11(17):5125. https://doi.org/10.3390/jcm11175125

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Velluzzi, Fernanda, Silvia Pisanu, Maura Galletta, Michele Fosci, Gianni Secci, Andrea Deledda, Francesco Boi, Rossella Rodia, Giuseppe Fanciulli, Alessandro Palmerio Delitala, and et al. 2022. "Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs)" Journal of Clinical Medicine 11, no. 17: 5125. https://doi.org/10.3390/jcm11175125

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