THE IMPORTANCE OF ANTHROPOMETRIC PAREMETERS IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM

Introduction: The concept of subclinical thyroid disease appeared in the 1980s when sensitive procedures for the measurement of the thyroid-stimulating hormone in the serum were introduced. Subclinical hypothyroidism is defined by the finding of elevated serum TSH concentrations with normal thyroid hormone levels. The incidence of subclinical hypothyroidism with increased cardiovascular risk has not yet been fully clarified. The aim of the study was to identify anthropometric parameters that may indicate an increased cardiometabolic risk in patients with subclinical hypothyroidism. Method: The study will include 140 patients aged 18-65, with 105 patients with subclinical hypothyroidism and a control group of 35 healthy, normally nourished subjects without subclinical hypothyroidism. A program of research will be carried out in all patients and it will include: detailed anamnesis and physical examination, anthropometric measurements (weight measurements, body height, waist circumference, hip circumference, body weight mass measurement by the bioelectrical impedance analysis method (%BFP), calculation of: body mass index (BMI), waist-to-hip circumference ratio (WC/HC), waist-to-height ratio (WC/Ht) and laboratory testing (FT3, FT4, TSH). Results: Examinees with subclinical hypothyroidism had statistically significantly elevated mean TSH values (6.87 + 1.34 mIU/ml) compared to TSH euthyroid examinees (1.9 + .88 mIU/ml). The mean age of subjects with subclinical hypothyroidism was 44.15 ± 11.23 years (MA = 43 years), and in subjects without subclinical hypothyroidism, 33.80 ± 10.60 years (MA = 33 years). In relation to the control group (euthyroid patients), patients with subclinical form of hypothyroidism had higher average mean values and statistically significantly higher incidence of elevated values: BMI (T test = 7.465, p < 0.0001; 2 = 35.977, p < 0.0001), %BFP (T test = 8.594, p < 0.0001; 2 = 44.956, p < 0.0001), WC (T test = 6.262, p < 0.0001; 2 = 48.865, p < 0.0001), and WC/Ht ratio (T test = 7.372, p < 0.0001; = 39.175, p < 0.0001). The WC/HC ratio in the group with subclinical hypothyroidism was higher than in the group without subclinical hypothyroidism, but not statistically significant (T test = -0.946, p = ns; 2 = 0.622, p = 0). Conclusion: In the subclinical form of hypothyroidism, changes in the degree of nutrition and body weight can already be recorded, which, among other things, contributes to the development of increased cardiometabolic risk.


INTRODUCTION
Subclinical thyroid dysfunction or "mild" thyroid disease is a common disorder, mainly in middle-aged and elderly people (1).
Subclinical hypothyroidism (SH) is defined by the finding of elevated serum TSH concentrations with the normal values of thyroid hormones (2,3).
Subclinical thyroid disease attracts attention and researchers reaffirm the need for the analysis of the possible meaning of this condition.
There are still controversial opinions about defining, clinical significance, the need for rapid diagnosis and the treatment of sub-clinical thyroid dysfunction (4) cardiovascular system by increasing the risk of mortality (2,3,(5)(6)(7)(8)(9)(10).Cardiometabolic risk presents a comprehensive risk of developing type 2 diabetes and cardiovascular disease as a result of multiple risk factors.The central type of obesity, dyslipidemia, glycosidic tolerance and hypertension disorder are its main characteristics (11,12).
In this study we proceeded from the assumption that changes in the size and distribution of body weight, which among other things contribute to the development of increased cardiometabolic risk, can be recorded in the subclinical form of hypothyroidism.

AIM OF THE STUDY
The aim of this study is to identify anthropometric parameters that may indicate an increased cardiometabolic risk in patients with subclinical hypothyroidism: BMI, body fat percentage, distribution of body weight (waist circumference, waist-to-hip ratio, waist-to height ratio).

MATERIALS AND METHOD
The study included 140 patients aged 18-65, out of whom 105 patients had subclinical hypothyroidism and 35 patients were the euthyroid controls.
The study was carried out according to the following protocol: 1. Obtaining history data.History data were obtained by means of structured history questionnaire.
3. Anthropometric measurements.The patients were examined in fasting state (not taking food 12 to 14h prior to testing).a) Measurement of body weight was performed by medical decimal scales with moving weights, with the precision of 0.1 kg.b) Body height was measured with Martin's anthropometer with the precision of 0.1 cm.c) Measurement of waist circumference was performed in the standing position at the level of the median distance between the costal arch and the anterior superior iliac spine.d) BMI was obtained as the quotient of body weight (kg) and body height (m2).
e) Measurement of the body fat mass was performed using the bioelectric impedance analysis procedure.Patients were recommended not to eat or drink anything at least four hours before measurement, to avoid physical activity 12 hours before measurement, not to take alcohol for 48 hours before measurement, not to take diuretics seven days before measurement, and to empty their urinary bladder 30 minutes before measurement.The body fat mass measurement was performed with Tanita Body Composition Analyzer BC-418 MA III (Tanita Corporation, MADE IN P.R.C.2004).
The study included patients who met all inclusion and had none of exclusion criteria.
Inclusion criteria were as follows: 1. Patients aged 18 to 65. Exclusion criteria: 1. Patients with diagnosed diabetes mellitus.
3. Chronic diseases that may have effect on studied parameters (systemic autoimmune diseases, malignant diseases, chronic renal failure, liver insufficiency, acute coronary syndrome and stroke within the last 6 months).
4. Recent use of radioactive iodine, thyroid surgery and external neck radiation.5. Pregnancy and breast feeding.
Forming study group: Criterion for patients to be enrolled in the subclinical hypothyroidism group and in the controls was TSH > 4.2 IU/mL and TSH £ 4.2UI/mL.
Recommendations by the International Diabetes Federation (IDF) of April 2005 were taken for the definition of abdominal obesity.IDF recommends that the waist circumference threshold for abdominal obesity should be > = 94 cm in men and > = 80 cm in women of European descent.
Before starting the statistical analysis, laboratory reports with the results of the patients' analyses were anonymized and all of them were granted identification numbers (for the protection of patient privacy, while patient data were only known to investigators).Electronic data base was created using the SPSS version 20.0.Mean, standard deviation (SD), median, minimum and maximum as well as normal distribution of all studied continuous variables (normal distribution of values within the group was analyzed using Kolmogorov-Smirnov test) were determined.To compare the mean values of the continuous variables, we used repeated-measure unifactorial ANOVA and the dependent sample T-test in normal distribution, or alternatively, Mann-Whitney U-test (non-parametric test, alternative to T-test), and Wilcoxon matched pairs test for the outcomes not following normal distribution, as well as c 2 test for the comparison of frequency of categorical (dichotomous) variables.P < 0.05 was statistically significant, with a 95% confidence interval.

RESULTS
The study included 140 patients aged 18-65, out of whom 105 patients had subclinical hypothyroidism and 35 patients were the euthyroid controls.
Testing the normality of the series (Skewness test), as well as determining the coefficient of variation (> 30%), it was shown that the mean TSH value of patients in the group with SH has a mean value which is statistically significantly higher than in patients without SH (Table 1).
The average age of patients with SH was 44.15 ± 11.23 years (MA = 43 years), and for patients without SH it was 33.80 ± 10.60 years (MA = 33 years).The mean age of 105 patients from the experimental group was statistically significantly higher than the mean age in 35 patients from the group without SH (analyzed using ANOVA test, p < 0.0001.(Table 2).
Testing the normality of the series (Skewness test), as well as determining the coefficient of variation (> 30%), proved that the following series of parameters that were monitored have a normal distribution (Table 3).      4 lists descriptive statistics of anthropometric parameters in relation to the groups, and the distribution of selected parameters in relation to the reference values and in relation to the groups is shown in Table 5.

With
Table 6 shows the results of testing of the tested parameters in the experimental group in relation to the control group with nonparametric tests.
In relation to the control group (euthyroid patients), patients with subclinical hypothyroidism had higher mean values and statistically significantly higher incidence of elevated values: BMI, % BFP, WC, and WC/Ht ratio (p < 0.0001).The WC/HC ratio in the subclinical hypothyroid group was higher than in the group without subclinical hypothyroidism, but not statistically significant (T test = -0.946,p = ns; c 2 = 0.622, p = 0).

DISCUSSION
In this study we found that in patients with SH, in relation to the control group of normally nourished persons without a thyroid gland function disorder, there are changes in the anthropometric parameters, especially in the degree of nutrition, as well as an increase in body weight, which among other things contributes to the development of increased cardiometabolic risk.
The prevalence of subclinical hypothyroidism in adult population is 4 to 8.5% (1,21).The prevalence increases with age, and in women over 60 years of age it is 20% (1,21).Annually, 2 to 5% of patients who have had subclinical hypothyroidism develop clinically expressed hypothyroidism.
The presence of hypothyroidism symptoms in patients with subclinical hypothyroidism remains controversial.Based on clinical symptoms, it is difficult to distinguish between a euthyroid person and a person with subclinical hypothyroidism.Many symptoms are non-specific and are related to the severity of the disease, the duration of the disease, the individual sensitivity of peripheral target organs to the deficit of thyroid hormones (4,23,24).
In their study (15), Kong and associates showed that women with subclinical hypothyroidism complained of fatigue (83%) and weight gain (80%).50% of women had an elevated level of anxiety (25).
A more recent review of the clinical consequences of thyroid function variations within the normal reference range documented that even modest elevations of TSH might have substantial health outcomes, including cardiovascular mortality (26).The results of meta-analyses of Yang et al. demonstrated that SH was significantly associated with a higher risk of MetS (27).
Metabolic syndrome (MetS) can be defined in different ways, but the central type of obesity, dyslipidemia, glycosidic disorder and hypertension disorder are its main characteristics.These criteria are consistent with the data obtained from the INTERHEART study, which showed that dyslipidemia, hypertension, abdominal obesity and diabetes are among the nine most significant risk factors that account for 90% of the population risk for myocardial infarction (28).
In 2005, IDF and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) (29-31) tried to agree on the criteria of the clinical definition of MetS.However, their recommendations differ in terms of waist circumference.
IDF recommends that the threshold for waist circumference in abdominal obesity should be > = 94 cm in men and > = 80 cm in women of European descent; AHA/NHLBI recommend values of > = 102 cm for men and > = 88 cm for women.
In our study of 105 patients in the SH group, the waist circumference was 90.88 ± 11.53 cm, and in the group without SH the waist circumference was statistically significantly lower, and it was 77.66 ± 8.24 cm (p < 0.0001).In the group with SH there were 19 patients (18.1%) with WC within the reference values, while 86 (81.9%) of the patients had elevated values of waist circumference.In the group without SH there were 29 patients (82.9%) with WC within the reference values, while 6 (17.1%) of the patients had elevated values of waist circumference (p < 0.0001).
The average value of HC in patients with SH was 103.62 ± 11 cm, and in patients without SH it was 87.49 ± 6.64 cm (p < 0.0001).
The relationship between hip and waist is an index that easily distinguishes two types of obesity from each other, not equally significant in terms of presenting the potential risk of morbidity.If this ratio was higher than 0.9 in women and 1.0 in men, obesity is abdominal (32).When analyzing the WC/HC ratio in the group with SH there were 43 patients (41%) with WC/HC within the reference values, while 62 (59%) patients had elevated WC/HC values.In the group without SH there were 17 patients (48.6%) with WC/HC within the reference values, while 18 (51.4%) of the patients had elevated WC/HC values (p = 0.430).
The relationship between waist and height is a better indicator of heart disease and diabetes than a body mass index, according to a new study recently presented by Dr Margaret Ashwell (32)(33)(34)(35)(36)(37).
In our study, the average value of the WC/Ht ratio of patients with SH was 0.55 ± 0.07, and for patients without SH it was 0.45 ± 0.04 (p < 0.0001).In the SH group there were 25 patients (23.8%) with WC/Ht within the reference values, while 80 (76.2%) of patients had elevated WC/Ht values.In the group without SH there were 30 patients (85.7%) with WC/Ht within the reference values, while 5 (14.3%) of the patients had elevated WC/Ht values (p < 0.0001).
According to the criteria of the World Health Organization, the BMI values between 18.5 and 24.9 kg/m Fat tissue plays an important role in MetS pathogenesis, promoting inflammation, hypertension, and dyslipidemia, which all contribute to the development of T2DM, atherosclerosis, and thrombosis.Body weight increment in patients with subclinical hypothyroidism may also contribute to the development of insulin resistance (39)(40)(41), which, in addition to the earlier understanding of the causes of increased cardiovascular risk, may have implications in explaining these etiopathogenetic relationships.The role of obesity in the onset of MetS can be seen from the correlation between the rise in the prevalence of MS and obesity in the United States and other countries (42)(43)(44).
In our study, the percentage of average fat mass body fat (% BFT) was statistically significantly higher in patients with SH (37.26) compared to patients without SH (24.56) (p < 0.0001).In the SH group, 28 patients (26.7%) were with BFP in reference values, while 77 (73.3%) patients had elevated% BFP values.In the group without SH there were 32 (91.4%) patients with% BFP within the reference values, while 3 (8.6%)patients had elevated %BFP values.
In conclusion, we can say that the results of this study suggest that patients with subclinical hypothyroidism have changes in anthropometric parameters, especially in the degree of nutrition, as well as in the increase in body weight, and on the whole, represent a category of people with elevated cardiovascular risk.Timely and precise identification of these parameters in patients with subclinical hypothyroidism opens the possibility of specific therapeutic intervention directed against the reduction of cardiovascular risk.
It is still an open question whether subclinical thyroid dysfunction can lead to fatal consequences for the

Table 1 .
Parameters of thyroid status in relation to the presence of SH FT3-free triodothyronine; FT4 -free thyroxine; TSH: thyroid stimulating hormone

Table 2 .
Mean age in relation to groups and T test SH: subclinical hypothyroidism

Table 4 .
Descriptive statistics of anthropometric parameters in relation to groups

Table 6 .
Testing the differences of the selected parameters by groups