title: Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6.
abstract: BACKGROUND
  The prevalence of metabolic syndrome increases after menopause; however, the role of concomitant subclinical hypothyroidism has not been completely elucidated. The aim of the study was to identify associations between thyrotropin, immune status, inflammation, and metabolic syndrome in postmenopausal women. The specific goals were: to assess thyrotropin (TSH) and interleukin-6 (IL-6) concentrations in the serum of subclinical hypothyroid postmenopausal women with and without metabolic syndrome and compare them with euthyroid controls; to test whether immune status is related to metabolic syndrome in postmenopausal women and determine the role of IL-6; to examine the relationships between TSH and different features of metabolic syndrome: insulin resistance, waist circumferences, waist-to-hip ratio (WHR), BMI, metabolic parameters (triglycerides, total cholesterol and high-density lipoprotein cholesterol), and inflammatory cytokines (IL-6).
  
  
  METHODS
  Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mL > TSH ≥ 4.5 uIU/mL, normal fT4), and 258 women were in euthyreosis (TSH 0.35-4.5 uIU/mL, normal fT4); both groups were matched by age. Anthropometric measurements were conducted (BMI, waist circumference, WHR) and blood pressure was measured. In all subjects the following were assessed in serum: lipid profile, glucose, insulin, TSH, fT4, thyroid antibodies (T-Abs) - TPO-Abs, TG-Abs, and IL-6 concentrations.
  
  
  RESULTS
  The prevalence of metabolic syndrome was 49.12% in subclinical hypothyroid women and 46.89% in euthyroid women. However, the proportion of subjects with one or two abnormalities was significantly higher in the subclinical hypothyroid group (45.61%) than in the euthyroid group (32.17%). When we compared subclinical hypothyroid women with and without metabolic syndrome, subjects with metabolic syndrome had higher BMI, abdominal circumferences, WHR, and HOMA-I. They presented higher systolic and diastolic blood pressure. Serum concentrations of cholesterol, triglycerides, fasting glucose, IL-6, TSH, T-Abs were also higher and serum cHDL was lower. There were no significant differences in fT4 concentrations. A similar comparison was made for euthyroid women with and without metabolic syndrome. Higher BMI, waist circumference, WHR, HOMA-I, and systolic blood pressure were observed in subjects with metabolic syndrome. Serum concentrations of TSH, triglycerides, glucose, and IL-6 were also higher, but the concentration of cHDL was significantly lower. There were no significant differences in fT4, T-Abs, cholesterol levels, and diastolic pressure. When we compared euthyroid women T-Abs (+) and T-Abs (-), the prevalence of metabolic syndrome was similar (48.68% vs. 46.15%). There were no differences in BMI, waist circumference, WHR, lipid profile, glucose, and HOMA-I, fT4. However, thyroid autoimmunity was associated with elevated TSH and IL-6 levels. When we analysed subclinical hypothyroid women with and without thyroid autoimmunity, there were no significant differences in glucose and lipid profile. However, Hashimoto`s subjects were more obese, had higher waist circumference, WHR, HOMA-I, and higher prevalence of metabolic syndrome. Serum concentrations of TSH and IL-6 were also higher and fT4 was lower. Among all of the women, serum TSH concentration was significantly correlated with BMI, waist circumference, WHR, systolic blood pressure, cholesterol, triglycerides, and TPO-Abs. When the variables of subjects with upper quartile of TSH were compared with lower quartile of TSH, we found significantly higher BMI, waist circumference, WHR, increased concentration of IL-6, cholesterol, triglycerides, and T-Abs, and concentrations of cHDL and fT4 were lower. OR for metabolic syndrome in subjects with upper quartile TSH vs. lower quartile was 1.35 (95% confidence interval [CI] 1.10-1.60).
  
  
  CONCLUSIONS
  Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role.
authors.affiliation: Department of Pathophysiology and Endocrinology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland. lusiem@poczta.onet.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Siemińska
authors.forename: Celina
authors.initials: C
authors.lastname: Wojciechowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Walczak
authors.forename: Artur
authors.initials: A
authors.lastname: Borowski
authors.forename: Bogdan
authors.initials: B
authors.lastname: Marek
authors.forename: Mariusz
authors.initials: M
authors.lastname: Nowak
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kajdaniuk
authors.forename: Wanda
authors.initials: W
authors.lastname: Foltyn
authors.forename: Beata
authors.initials: B
authors.lastname: Kos-Kudła
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood; D015850:Interleukin-6 / Q000097:blood* / Q000502:physiology; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D013961:Thyroid Gland / Q000276:immunology*; D013972:Thyrotropin / Q000097:blood*
chemical_list: D001323:Autoantibodies; C508600:IL6 protein, human; D015850:Interleukin-6; D013972:Thyrotropin
keywords: autoimmune thyroiditis; interleukin-6; metabolic syndrome; subclinical hypothyroidism