Normal TSH Group Research Articles

Association of thyroid hormones with metabolic syndrome and its components in postmenopausal Chinese women

To evaluate the association between thyroid hormones (TH) and metabolic syndrome (MS) in postmenopausal women (PmW), a cross-sectional study was conducted with a sample of 1000 participants of PmW (40–65 years). Thyroid stimulating hormone (TSH) and free thyroxine (fT4) were evaluated. The MS was defined using the International Diabetes Federation (IDF) ethnicity-specific definitions for Asian. Participants were classified into three groups according to the TSH reference range: high-TSH (≥4.2 mU/L), low-TSH (<0.1mU/L), and normal-TSH (0.1–4.2 mU/L) group. Serum triglycerides (TG) levels were higher in low-TSH group and high-TSH group compared with normal-TSH group (p < .05). The whole sample was stratified into <60 and ≥60 years subgroups. In the ≥60 years group, fT4 was negatively correlated with waist circumference (WC) (p = .028) and positively correlated with fasting blood glucose (FBG) (p = .043), meanwhile TSH was positively correlated with WC only in the control subjects (p = .014). No difference was found between TH and the number of MS components. It was demonstrated that serum fT4 levels were associated with FBG and WC, while TSH was associated with WC in elderly PmW without MS.

Prevalence of thyroid dysfunctions in infants and children with Down Syndrome (DS) and the effect of thyroxine treatment on linear growth and weight gain in treated subjects versus DS subjects with normal thyroid function: a controlled study.

Background: Individuals with Down syndrome (DS) are at an increased risk of developing thyroid disease, primarily autoimmune, with a lifetime prevalence ranging from 13% to 63%. Unfortunately, there are few studies systematically examining the frequency of thyroid disease in very young children. Aim of the study: The aim of the present study was to investigate the prevalence of different thyroid dysfunctions (TD) in a cohort of infants and children with DS and the growth parameters in subjects with normal versus abnormal thyroid function, followed for 3 years. Patients and methods: All children (n = 102; 48 males and 54 females, aged 2.3±3 years) with the diagnosis of DS who were seen at the General Pediatric Clinic of Hamad General Hospital in Doha (Qatar) from 2014 to 2018 were enrolled in our study. We recorded thyroid function and linear growth parameters [BMI, length/height SDS (Ht-SDS) and weight gain/day] and divided them into 3 groups according to their thyroid function. Group 1: (n = 36 subjects) with normal free T4 (FT4) and TSH; Group 2 (n = 44 subjects) with high TSH >5 and <12 mIU/L, and normal FT4, and Group 3 (n = 22 subjects) with TSH >12 mIU/L and/or FT4 <9 pmol/L. We also compared linear growth parameters in subjects with DS and thyroid dysfunction versus those with normal thyroid function at diagnosis and after treatment with L- thyroxine, for an average of 3 years. Results: In infants with DS (<1 year of age; n = 47, mean age: 5±3.5 months) we documented a higher prevalence of hypothyroidism (HT) (7/47 = 14.9%), both primary (5/47; 10.6%) and secondary (2/47; 4.3%). Subclinical hypothyroidism and positive thyroid antibodies were found in (13/47; 27.7%) and (9/47;19%, respectively). Before treatment with L-thyroxine, DS infants of Group 3 had significantly lower BMI-SDS but were not significantly shorter compared to other two Groups (p= 0.03 and p =0.14, respectively). After an average of 3 years of treatment the BMI- SDS and Ht-SDS did not differ among the treated and not treated infant groups. In the older group (>1 year; n=55; mean age: 5.5±3.3 years) primary HT was detected in 7/55 (12.7%). Subclinical HT was diagnosed in 20/55 (36.4%) and positive thyroid antibodies were found in 26/55 (47.3%). Before treatment with L-thyroxine, using the CDC growth charts for DS, we found that the groups with high TSH (Groups 2 and 3) were significantly shorter and heavier compared to the group with normal TSH (Group 1). After treatment with L-thyroxine, the Ht-SDS and Wt-SDS did not differ between the two groups. The linear growth of those diagnosed early during the first year of life was compared to growth parameters of children who were diagnosed with thyroid dysfunction later in life. Conclusion: Our data provided more evidence to support the findings that L- thyroxine treatment can improve growth of infants and young DS children with high TSH (>5 mIU/L), especially in those with TSH >12 mIU/L. (www.actabiomedica.it)

Investigating the relationship between 25-hydroxyvitamin D and thyroid function in second-trimester pregnant women

This study aims to explore the correlation between serum 25-hydroxyvitamin D and thyroid hormones during the second trimester. In total, 277 pregnant women at 13–28 weeks of gestation were enrolled. According to the level of thyrotropic-stimulating hormone, they were divided into a reduced TSH group, a normal TSH group and an elevated TSH group. In this study, we found that the prevalence of vitamin D deficiency was as high as 94.58%. The 25-hydroxyvitamin D level in the reduced TSH group was lower than that in the normal thyroid function group (p = .0005), and the 25-hydroxyvitamin D level in the elevated TSH group was higher than that in normal TSH group (p=.0339). A positive correlation was observed between 25-hydroxyvitamin D and thyrotropic-stimulating hormone (r = 0.3034, p = .0000). Furthermore, 25-hydroxyvitamin D was negatively correlated with the free thyroxine level (r = −0.1286, p = .0323) as well as the free triiodothyronine level (r = 0.1247, p = .0380). These data suggest that the relationships between 25-hydroxyvitamin D and thyroid parameters were characterized during the second trimester. Pregnant women in the second-trimester who are diagnosed with transient hyperthyroidism should be evaluated for the possibility of vitamin D deficiency.

Association Between Serum Thyrotropin Levels and Mortality Among Euthyroid Adults in the United States.

Low thyroid function within the euthyroid range, as well as overt and subclinical hypothyroidism, reportedly increases the risk of cardiovascular disease and mortality. However, the association between low normal thyroid function and mortality remains controversial. This study was performed to elucidate the association between low normal thyroid function and all-cause and/or cause-specific mortalities among U.S. adults. A prospective cohort study was conducted using a nationally representative sample of 12,584 U.S. adults aged ≥20 years with thyrotropin (TSH) levels within the reference range from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Associations between TSH tertiles (high, medium, and low normal TSH groups) and mortalities (all-cause, cardiovascular, and cancer) were investigated using multivariable Cox models. Stratum-specific analyses were estimated within subgroups defined according to sex (male or female) and baseline age (age <60 years or age ≥60 years). Further, the same analysis was conducted using continuous NHANES 2001-2002, 2007-2008, and 2009-2010 cohorts, which included data on free thyroxine levels. The median follow-up period was 19.1 years, with 3395 all-cause deaths. A significantly higher risk of all-cause mortality (adjusted hazard ratio [HR] 1.27; [confidence interval (CI) 1.10-1.47]), and cardiovascular mortality (HR 1.30 [CI 1.02-1.67]), and cancer mortality (HR 1.43 [CI 1.01-2.01]) was observed in the high normal TSH group than in the medium normal TSH group. Additionally, the low normal TSH group had an increased risk of all-cause mortality. In stratum-specific analyses, a significant association was found between high normal TSH levels and all-cause mortality among males, females, and participants <60 years. Continuous NHANES cohorts demonstrated a non-significant increase in the HR for all-cause mortality in the high normal TSH group. High normal TSH levels compared with medium normal TSH levels were associated with increased risk of all-cause, cardiovascular, and cancer mortalities over a long-term follow-up period among U.S. adults. This study indicates that the reference range for TSH levels may require re-evaluation.

Metabolic Characteristics in Obese Patients Complicated by Mild Thyroid Hormone Deficiency.

The prevalence of subclinical hypothyroidism (SH) is increasing, especially in obese people. The purpose of this study was to evaluate the difference in metabolic profiles between obese patients with mild increased thyrotropin (TSH) or with normal TSH. A total of 219 obese patients were recruited in this cross-sectional study. They were divided into 2 groups: obese patients with normal TSH (0.35-2.5 mU/l) and age-, and body mass index (BMI)-matched obese patients with higher-normal TSH (2.5-5.5 mU/l). We have named it compensatory hypothyroidism or mild thyroid hormone deficiency. Anthropometric data, glucose-lipid metabolism, markers of inflammation, body composition, and thyroid function parameters were measured. Results showed that: 1) The levels of fasting plasma glucose (FPG), high density lipoprotein cholesterol (HDL-C), and 25-hydroxyvitamin D levels were significantly lower in obese patients complicated by mild increased TSH than in obese patients with normal TSH (p<0.05). The fasting insulin (FINS) and C reactive protein (CRP) levels were significantly higher in obese patients complicated by mild increased TSH when compared to the obese patients with normal TSH (p<0.01). Jostel's TSH index (TSHI) and standard TSH index (sTSHI) were significantly higher in obesity with mild increased TSH when compared to obesity with normal TSH (both p<0.001). Thyroid's secretory capacity (GT) was significantly lower in obesity with mild increased TSH when compared to obesity with normal TSH (p<0.001). 2) In the obese patients complicated by mild increased TSH group, serum TSH was significantly positively correlated with ALT, AST and CP (p<0.05). In the obese patients with normal TSH group, serum TSH was significantly positively correlated with UA (p<0.05). In all subjects, serum TSH was significantly positively correlated with ALT, AST, FINS, CP, CRP, and UA (p<0.05), but negatively with DBP, FPG, and HDL-C (p<0.05). 3) There was significant difference of the prevalence of hyperinsulinemia and impaired fasting glucose (IFG) between the 2 groups (p<0.05). In Conclusion, obesity complicated by mild increased TSH manifested higher fasting insulin levels, more severe chronic low-grade inflammation, and lower HDL-C levels than obesity with normal TSH.

Abstract 216: Left Ventricular Diastolic Dyssynchrony In Patients With Treatment-naïVe Hypertension And The Effects Of Antihypertensive Therapy

Backgrounds: We tried to investigate whether differ in various blood pressure (BP) parameters between the patients with low normal TSH and high normal TSH levels. Methods: The study groups consisted of 285 patients with treatment-naïve hypertension and euthryoid undergoing comprehensive echocardiography (TTE), brachial-ankle pulse wave velocity (PWV), ankle-brachial index, central BPs, and ambulatory BP monitoring (ABPM) evaluations. All patients were divided into those with low normal TSH (0.40~1.99 μIU/ml, group 1) or high-normal TSH (2.00-4.50 μIU/ml, group 2). Results: Hypertensive male patients were divided into group 1 (n=113, 68.9%) and group 2 (n=51, 31.1%) and female patients were divided into group 1 (n=71, 58.7%) and group 2 (n=50, 41.3%). Multivariate analyses revealed augmentation index (AIx, 71.0 [adjusted mean]±1.7 [standard error] vs. 78.8±2.5 %, p=0.045), central systolic BP (SBP) (143.3±2.1 vs. 153.0±3.2 mmHg, p=0.013), systemic vascular resistance (21.4±0.6 vs. 23.9±0.9 mmHg/L/min, p=0.027), and SBP in daytime (144.1±1.4 vs. 151.6±2.1 mmHg, p=0.004) and nighttime (130.4±1.6 vs. 138.5±2.5 mmHg, p=0.008), and nighttime pulse pressure (PP, 47.2±0.9 vs. 51.7±1.4 mmHg, p=0.010) were significantly higher and cardiac output (5.4±0.1 vs. 4.8±0.2 L/min, p=0.043) and PP amplification (1.02±0.02 vs. 0.94±0.03, p=0.039) were significantly lower in male group 2. After multivariate analyses, SBP (β=0.225, p=0.010) and PP (β=0.179, p=0.022) at office, PWV (β=0.192, p=0.036), AIx (β=0.285, p=0.007), central SBP (β=0.351, p=0.001), DBP (β=0.246, p=0.012), and PP (β=0.317, p=0.006), SBP in daytime (β=0.219, p=0.004) and nighttime (β=0.232, p=0.013), and PP in 24-hour (β=0.216, p=0.005) and nighttime (β=0.172, p=0.024) were linearly associated with levels of TSH in hypertensive male. Conclusion: Despite euthryoid, arterial stiffness, central SBP, and SBP in ABPM are higher and cardiac output and PP amplification are lower in high normal TSH group of treatment-naïve hypertensive male, but not female. Arterial stiffness, SBP and PP at office, central BPs, and SBP and PP in ABPM are linearly associated with TSH levels among hypertensive male.

The Effect of Thyroid-Stimulating Hormone on Tumor Size in Differentiated Thyroid Carcinoma.

We evaluated the correlation between serum thyroid-stimulating hormone (TSH) levels and tumor size and other invasiveness parameters of tumor in patients with differentiated thyroid carcinoma (DTC). Several clinical studies have reported that TSH may also have a role as a regulator of the development and function of the thyroid gland. It is currently not clear whether TSH is involved in the existence of thyroid cancer or progression of thyroid cancer or both. Patients with DTC who underwent thyroid surgery between 2003 and 2008 were included this study. Preoperative serum T3, T4, and TSH levels were compared with the size and invasiveness of cancer, retrospectively. DTC was observed in 110 patients over the 5-year period. Seventy-seven (70%) of them were euthyroid and classified as the "normal-TSH group" (NTG), and 33 (30%) have an overt or subclinical hyperthyroidism, classified as the "low-TSH group" (LTG). The mean tumor diameter in the LTG was found to be 8.91 ± 8.03mm; however, it was found to be 18.19 ± 16.24mm in the NTG. There were significantly differences among the groups related to the diameter of tumor (p = 0.001). Microcarcinoma was determined in 36 patients (46.8%) in the NTG and 23 patients (69.7%) in the LTG (p = 0.027). Although there were no significant differences, tumor capsule invasion (33.8 vs. 18.2%, p = 0.099) and lymphovascular invasion (16.9 vs. 6.1%, p = 0.130) rates were higher in the NTG. These findings suggest that TSH has effects on growing and proliferation of not only normal thyroid cells but also cancer cells in DTC. This study revealed that serum TSH level can be explored as an important factor that affects the size and invasiveness of tumor in DTC.

Effects of maternal subclinical hypothyroidism on obstetrical outcomes during early pregnancy.

Maternal hypothyroidism [overt hypothyroidism and subclinical hypothyroidism (SCH)] during early pregnancy is suspected to associate with adverse obstetrical outcomes. The aim of the present study was to investigate whether maternal SCH during the early stage of pregnancy increase obstetrical complications and whether treatment results in an improvement in these outcomes. A total of 756 women in the 1st trimester (≤12 weeks) of pregnancy were enrolled through 10 hospitals in Shenyang from 2007 to 2009. All participants underwent thyroid function testing in early pregnancy and their obstetrical outcomes were studied following delivery. The incidence of spontaneous abortions in the SCH group was higher than the normal TSH group (15.48% vs 8.86%, p=0.03). No significant association was observed between SCH and other obstetrical complications including gestational hypertension, premature delivery, anemia, post-partum hemorrhage, low neonatal Apgar scores and low birth weight. Although levo-T4 (L-T4) treatment decreased the incidence of spontaneous abortions in women with SCH, it was not statistically significant when compared to women who did not receive treatment in the SCH group. None of the 28 women who received L-T4 treatment had premature delivery, low birth weight, hemorrhage, and low Apgar score. The incidence of spontaneous abortion in pregnant women with SCH increases in early pregnancy.

Basal Thyrotropin and Major Depression: Relation to Clinical Variables and Treatment Outcome

There is a current argument in thyroidology about whether the normal range for basal thyrotropin (TSH) is too broad. Some groups suggest that a TSH of less than 2.5 mIU/L is a better cut-off for euthyroidism. Because major depression is associated with changes in thyroid hormone status and thyroid hormones may be an effective treatment for major depression, we examined whether TSH levels above or below 2.5 mIU/L were related to clinical variables or treatment outcome in euthyroid patients with major depression. Outpatients with major depression (n =166) were assigned to high-normal and low-normal TSH groups based on their basal TSH levels. The 2 groups were compared along clinical variables and treatment outcome. The low-normal TSH group was significantly more depressed, as measured by Hamilton Depression Rating Scale scores, and had more anxiety symptoms and suicidal tendencies than the high-normal group. There was no difference in treatment response between the groups. A comparison of low-normal and high-normal basal TSH groups with major depression revealed significant differences in severity and symptoms of depression but no difference in treatment outcome. These data are preliminary and require replication in a larger sample.

An association between thyroid disease and breast cancer

21063 Background: Anecdotal studies and isolated case reports have observed an association of thyroid disease and breast cancer. This purported association remains controversial. We describe a retrospective case-control study on the prevalence of breast cancer in patients with abnormal thyroid function studies. Age-matched subjects served as controls. Methods: We reviewed 6211 cases of abnormal TSH values between 1/04 and 12/05 and determined the number of cases with breast cancer. We compared those data to 3,151 control subjects with normal TSH seen during the same period. We excluded patients with thyroid cancer from the total number of malignancies in both groups because abnormal TSH would be expected to result from its treatment. We also reviewed the ER, PR, her 2 neu status and free thyroxine of patients with breast cancers. Results: Breast cancer rate of 36% of all cancers (37/102) in the abnormal TSH group was significantly higher than that of 18% (14/77) in the normal TSH group. (p = 0.012). Breast cancers in the study group with abnormal thyroid function were more frequently hormone receptor positive (74% vs. 67%) and her 2 neu negative (67% vs. 50%). Conclusions: The data suggest that there is an increased rate of breast cancer in patients with abnormal thyroid function. The trend of hormone receptor positive disease in the abnormal TSH group suggests that the IGF receptor may play an important role in the relationship between thyroid disease and breast cancer. The IGF receptor may be a potential target for therapeutic drug development for breast cancer prevention and management. Further studies are warranted. No significant financial relationships to disclose.

Prevalence of Subclinical Hypothyroidism in a Morbidly Obese Population and Improvement after Weight Loss Induced by Roux-en-Y Gastric Bypass

There are many studies concerning thyroid function in obesity, and some of them describe higher TSH levels in obese subjects. Few studies evaluated long-term changes in thyroid function caused by weight loss after bariatric surgery. Our aims were to evaluate the prevalence of subclinical hypothyroidism (SH) in a morbidly obese population and to analyze the effect of weight loss induced by Roux-en-Y gastric bypass (RYGBP) on TSH and thyroid hormone (TH) levels. TSH, free thyroxine (fT4) and total triiodothyronine (T3) levels were analyzed before and 12 months after RYGBP in patients with grade III or grade II obesity with co-morbidities. Subjects taking TH and/or with positive antithyroid antibodies and/or with overt hypothyroidism were excluded. 72 subjects (62F/10M), with mean age 39.6+/-9.8 years and mean BMI 53.0+/-10.4 kg/m2 were studied. The prevalence of SH before RYGBP was 25% (n=18). There was a significant post-surgical decrease in BMI in the whole population, as well as in SH patients. In the SH group and normal TSH group, there was a decrease in TSH and T3, but not in fT4. TSH was not correlated with initial BMI or percent change in BMI. TSH concentrations reached normal values in all SH patients after RYGBP. Our data confirm that severe obesity is associated with increased TSH. The decrease in TSH was independent of BMI, but occurred in all SH patients. A putative effect of weight reduction on the improvement of SH in all patients may be an additional benefit of bariatric surgery.

Thyroid antibodies and tumor necrosis factor-a in patients with benign thyroid nodules treated by percutaneous ethanol injections

Treatment of benign thyroid tumors with percutaneous ethanol injections (PEI) is an alternative to radioiodine and surgery. This procedure causes a release of large amounts of denaturated thyroglobulin within the gland which may become an autoantigen, triggering the mechanism of autoimmunization. The aim of the study was to investigate whether ethanol injections can induce increased levels of thyroid autoantibodies and tumor necrosis factor-alpha (TNF-alpha) in patients with nonfunctioning or pre-toxic thyroid nodules. Thirty-four patients (31 F, 3 M) with single benign thyroid tumors were enrolled, 23 (20 F/3 M) with nonfunctioning nodule (group 1) and 11 (F) with pre-toxic nodule characterized by normal free thyroid hormones and low TSH (group 2). Under sonographic guidance, sterile 96% ethanol solution was injected into thyroid nodules at 2-week intervals up to a dose of 0.7-1.0 ml of ethanol per 1.0 ml nodule volume. TSH, fT4, thyroglobulin antibodies and thyroperoxidase antibodies as well as TNF-apha levels were assessed prior to alcohol administration and 3, 6, and 12 months after the end of treatment. PEI treatment decreased tumor volume by 75.8% in group 1 and by 80.4% in group 2, and normalized TSH level in 90.9% of patients with pre-toxic nodules. No statistically significant differences in thyroperoxidase antibodies and TNF-alpha levels were observed during the study period in both groups. Thyroglobulin antibody levels increased significantly 6 months after treatment in both groups, but returned to the baseline levels after 12 months. No significant difference in peak thyroglobulin antibody levels between the two groups was seen. PEI procedure is a safe method for treating nonfunctioning and pre-toxic thyroid nodules since this treatment reduces tumor size significantly without inducing long-lasting autoimmune reactions in the thyroid gland. Transient increase in thyroglobulin antibodies indicates that this procedure should be performed with caution in patients at risk of autoimmune diseases.

Estudo longitudinal do eixo hipófise-tireóide durante a gravidez

The thyroid undergoes important changes during pregnancy. In order to evaluate changes of the hypophyseal-thyroid axis during this period we studied the thyroid function in 587 pregnants by determining serum TSH, free T4, TPO antibodies and betahCG in the 1st trimester and serum TSH, free T4 and TPOAb in to 2nd and 3rd. We observed a progressive rise in average serum TSH in the 2nd (2.14 mU/L) and 3rd (2.96 mU/L) trimesters when compared to the 1st (1.39 mU/L). Serum TSH values in the 1st trimester were inversely correlated with betahCG levels in as much as TSH levels below 0.4 mU/L corresponded to average betahCG levels of 129,000 UI/L whereas these were 34,200 UI/L in the normal TSH group. A slight decrease in free T4 levels was also observed in the 2nd and 3rd trimesters (averages 1st: 1.15; 2nd: 0.99; 3rd: 0.94 ng/dl). Thyroid autoimmunity defined as positive TPOAb occurred in 13.9% of our patients during pregnancy. No significant differences in TSH and free T4 medium values were found between patients with positive TPOAb and those without. However, a significantly higher proportion of pregnants had abnormal hormonal values throughout the trimesters. We conclude that thyroid function is affected by pregnancy with a tendency for decline as it progresses, a feature more easily observed in positive TPOAb group.

Studies on hypophyseo-thyroid function in patients with chronic thyroiditis (author's transl)

It is well known that serum TSH levels are elevated in most patients with chronic thyroiditis, even if the patient exhibits normal thyroid function tests. The determination of serum TSH levels in these patients is thought to be the most sensitive indicator of subclinical hypothyroidism. In this study, the hypophyseo-thyroid functions of untreated euthyroid patients with chronic thyroiditis were evaluated. Serum T3 levels in most of these patients were raised or at high normal levels, although serum T4 levels were in the low normal range. Serum T4 levels in patients with raised basal TSH were distributed in the low normal range. Hence, it is suggested that the decreased serum T4 stimulates TSH secretion which in turn stimulates T3 (and T4) secretion from the thyroid and the elevated T3 maintains the patient's euthyroid condition. Basal TSH levels in these patients varied from 2.5 to 37.0 muU/ml and mean +/-SD was 12.9+/-9.6 muU/ml. Thirteen out of 30 patients (43%) with normal free T4 indices showed elevated basal TSH levels. TSH responses to TRH injection were exaggerated in all euthyroid patients with raised basal TSH levels, as well as in 11 out 14 patients (78.6%) with normal basal TSH levels as well. But the maximum TSH responses after TRH injection were well correlated with basal TSH levels (gamma=0.79). The percent increases of serum T3 after TRH injection in those patients were less than those of the normal person, and there was no difference in T3 response between the normal TSH group and the group with raised TSH. Eight patients who suffered from collagen diseases (SLE:6, RA:1, PSS:1) without any evidence of thyroid disease also exhibited exaggerated TSH responses to TRH. In five out of these eight patients (62.5%) antithyroglobulin antibody was positive. This may indicate the presence of the so-called asymptomatic autoimmune thyroiditis in these patients. It is suggested that the elevated basal TSH levels in euthyroid patients with chronic thyroiditis are a much more sensitive indicator of thyroid failure than any other routine thyroid function tests. Moreover, the exaggerated TSH responses to TRH in patients with normal basal TSH levels indicated that the TRH-test is more useful for the detection of minimal thyroid failure, especially in patients having such conditions as asymptomatic automimune thyroiditis.