Thyroid Stimulating Hormone Reference Range Research Articles

Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study.

Background and Objectives: Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods: A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions: Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

A-338 TSH Reference Range in the First Trimester in a Iodine Sufficient Population of Pregnant Women Attended by the Public Health System in Curitiba South of Brazil

Abstract Background Thyroid diseases are common among women of reproductive age, and the serum concentration of thyroid-stimulating hormone (TSH) is the most used index to assess thyroid function during pregnancy. Changes in thyroid function during pregnancy can have a clinical impact on a woman's health and pregnancy outcome, as well as interfere with fetal health and child development. An adequate thyroid function is essential for normal intrauterine development. When comparing the levels of TSH between pregnant and non-pregnant women, TSH levels are lower in pregnancy, mainly in the first trimester, with gradual increase during pregnancy. Although some guidelines propose fixed TSH reference values in pregnancy according to the gestational trimester, the main recommendation is to carry out a study of their local population due to the significant variation in TSH reference range levels in different populations and different assays. Therefore, it is necessary to determine values of a reference interval for TSH for the local population of pregnant women. This study aims to determine the normal reference range of TSH in the first trimester of gestation in the public health system pregnant women from Curitiba. Methods This is an ongoing prospective cohort study, with the population sample from the pregnant women using the public health system, with age >18 years old in Curitiba, South of Brazil. 383 pregnant women were invited to participate. After evaluate the exclusion criteria (gestational age more than 13 weeks, twin pregnancy, thyroid disease, iodine ingestion, identification of the samples in the laboratory), 225 pregnant women had the TSH measured by chemiluminescent immunoassay on Atellica IM Analyzer (Siemens Healthineers), as well as the TPO-ab presence, FreeT4 and Total T4. The 2.5, 50 end 97,5 TSH percentiles were estimated for the normal pregnant population. Results The mean gestational age was 8,6 weeks (standard deviation 2.33). From 225 pregnant women, 22 (9.8%) had TPO-ab positive. The 2.5 and 97.5 percentiles of TSH were 0.12 and 5.28 μIU/mL after using de exclusion criteria. The populational iodine status was sufficient. In the TPO-ab positive population was found a higher level of TSH. The proportion of TPO-ab positive was significantly higher in the population with TSH >2.5 μIU/mL. Conclusions This preliminary data shows the TSH reference range with levels higher than other regions, reinforcing to do not use fixed values of TSH from other populations to evaluate the thyroid function in pregnancy. Comparing to the laboratory reference for non-pregnant adult (0.48 to 5.60 μIU/mL), the recommended reduction of 0.5 μIU/mL on upper limit and 0.4 μIU/mL on the lower limit found similar values to our findings.

Corrigendum: Abstract and Text Correction. Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015.

Corrigendum: Abstract and Text Correction. Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015.

Impact of Thyroid Function on the Prevalence and Mortality of Metabolic Dysfunction-Associated Fatty Liver Disease.

Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.

Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population

The overdiagnosis of subclinical hypothyroidism (SCH) in the elderly has driven researchers to establish age-specific thyroid stimulating hormone (TSH) intervals to precisely evaluate the prevalence of SCH. Moreover, abnormal lipid profiles, an insidious manifestation of SCH, show various impacts on different age groups. This study aimed to establish an age-specific TSH reference range to clarify the spectrum of SCH in the elderly. The prevalence of dyslipidemia and the age-specific association between TSH and lipid profiles were analyzed to elucidate the relationship between SCH and dyslipidemia. This cross-sectional study enrolled 2460 participants aged ≥ 65 years via cluster sampling. All participants received physical, laboratory tests and thyroid ultrasound examination and completed the questionnaire. The chi-square test was used to analyze variations of dyslipidemia prevalence among different groups. The Cochran-Armitage trend test was applied for testing the linear trends of age-specific prevalence of dyslipidemia among different TSH intervals in each age group. After adjusting for confounding factors, the age-specific association between TSH and lipid profiles was identified using multi-variate linear regression analysis. The TSH reference ranges in the 65–70 age group, 71–80 age group and > 80 age group were 0.65–5.51 mIU/L, 0.85–5.89 mIU/L and 0.78–6.70 mIU/L, respectively. Using these age-specific reference ranges, the prevalence of SCH in the whole population was 3.74%, which was significantly lower than the prevalence based on the laboratory reference range (10.28%). In the 65–70 age group, only the prevalence of high total cholesterol (TC) increased significantly with the age-specific TSH intervals, and TSH was positively associated with TC and low-density lipoprotein cholesterol (LDL-C). In the 71–80 and > 80 age groups, the prevalence of high TC, high triglycerides (TGs), and high LDL-C increased significantly with elevated TSH reference ranges. The levels of TC, TGs, and LDL-C were also positively associated with TSH level in 71–80 age group. However, such an association disappeared in > 80 age group. An age-specific reference range for TSH can effectively prevent the overdiagnosis of SCH in the elderly. Aging could somewhat attenuate the impact of TSH on lipid profiles.

Relationship between the Thyroid Function and Cognitive Impairment in the Elderly in Japan.

Objective The reference ranges of serum thyroid hormone levels are determined by the values of normal subjects aged 15 or 20 to 60 years old in Japan and may differ from the values in elderly patients. In addition, the relationship between the thyroid function and cognitive function remains controversial. We assessed the thyroid function of elderly subjects ≥60 years old and its impact on the cognitive function in Japanese adults. Methods We compared the thyroid function by age group and gender and investigated the effects of cognitive impairment on the thyroid function. This study was a cross-sectional, multi-institutional joint study. Patients The serum concentrations of thyroid hormones in 1,136 patients were measured; however, those taking thyroid hormones, anti-thyroid drugs, and steroid hormones were excluded. Among them, 1,016 cases in which the cognitive function was evaluated were divided into five groups according to their free thyroxine (FT4) levels. Results Excluding overt thyroid dysfunction (5.8%), the average age of the 1,070 remaining patients was 77.5 years old. The rate of cognitive impairment was lowest at FT4 levels of 1.1-1.2 ng/dL and highest at FT4 levels <0.9 ng/dL for both genders. Thyroid-stimulating hormone (TSH) levels in the elderly varied widely by age group and gender. The upper limit of the reference range of TSH for those ≥60 years old may be higher (7.7-9.2 mIU/L for men; 8.2-8.6 mIU/L for women) than the current range for those <60 years old (4.23 mIU/L). Conclusion The thyroid function seemed to be slightly higher (lower TSH and higher FT4) in the population without cognitive impairment than in those with cognitive impairment, except for men in their 90s.

Regional Differences in Thyroid Function Parameters: A Comparison of European Cohort Studies

The aim of the project was to investigate regional differences in thyroid stimulating hormone (TSH), and free thyroxine (fT4) concentrations and iodine status in comparable German and European cohort studies. Sex- and age-stratified TSH, fT4, and urine iodine concentrations of thyroid-healthy participants (age group 45-75 years) of the HNR (Heinz Nixdorf Recall) Study in the Ruhr region of Germany, the southern German KORA (Cooperative Health Research in the Augsburg Region) and northeastern German SHIP (Study of Health in Pomerania) studies, as well as the Norwegian HUNT (Nord-Trøndelag Health) study (age group 40-79 years), the English EPIC (European Prospective Investigation of Cancer)-Norfolk study, and the Dutch Rotterdam study were compared. The TSH reference range for the HNR study population was calculated and compared to the KORA and SHIP studies. Regional differences showed a stronger influence on TSH and fT4 concentrations than sex and age of the subjects in the 45- to 75-year age group. The estimated difference in medians, as measured by the HNR study, was lowest in the SHIP study, -0.47 (95% CI: -0.53; -0.41) for men and -0.41 (-0.53; -0.41) for women. The Rotterdam study had the highest difference in medians for both men and women (men: 0.56 with 0.44; 0.68 and women: 0.62 with 0.46; 0.78). The lowest median TSH concentrations, across all age categories considered, were seen in the German cohorts. Comparison of thyroid function parameters and iodine in elderly subjects between six comparable cohort studies from Germany and Europe showed a significant influence of region, which exceeded the sex and age dependence of the parameters.

Optimal Serum Thyroid-Stimulating Hormone Level for Patients With Papillary Thyroid Carcinoma After Lobectomy

Background: The optimal serum thyroid-stimulating hormone (TSH) level for post-lobectomy papillary thyroid carcinoma (PTC) patients is unclear. The objective of this study was to examine the association of TSH and recurrence in post-lobectomy patients. Methods: Patients who underwent lobectomy for PTC in a single tertiary hospital from January 2000 to December 2014 were enrolled. The mean TSH score of a patient was calculated based on each serum TSH value during follow-up. The TSH value of each follow-up visit was scored as 0-20 with an interval of 0.5 mU/L, and the mean TSH score (MTS) was calculated as the average of all available scores for a patient. The reference range of serum TSH was 0.5-4.0 mU/L (MTS 0-7). Univariate and multivariable analyses were performed with Cox proportional hazards models. Restricted cubic spline (RCS) functions were used to model relationships between MTS and recurrence-free survival (RFS). Results: A total of 2297 patients (median age, 42 years; 1750 (76.2%) female) were analyzed. MTS below (≤0.5), in the lower half (0.5-3), in the upper half (3-7) and above (>7) the reference range were observed in 415 (18.1%), 1376 (59.9%), 409 (17.8%), and 97 (4.2%) patients, respectively. According to the Cox model and RCS, no association was observed between MTS and RFS (adjusted P=0.5071, adjusted P for nonlinear=0.5182). The only RFS difference observed in the stratified univariate analysis was between patients with MTS in the lower half (n=793) and above the reference range (n=54) in the intermediate- to high-risk group (10-year RFS by Kaplan-Meier 82.1% vs 70.5%, log rank p=0.023). Conclusions: Mean serum TSH levels are not associated with recurrence. A normal TSH reference range is recommended for post-lobectomy PTC patients. Funding Information: The study was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2m-1-002) and Beijing Hope Run Special Fund of Cancer Foundation of China (Grant no.LC2018A26) Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained at the time of surgery with surgical consent for general use of clinical information for future studies.

Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape.

Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome

BackgroundLow free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI.MethodsPatients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality.ResultsOne hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42–5.552, P = 0.003).ConclusionsLow FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

Thyroid Disorders in Pregnancy: Role of Routine Antenatal Thyroid Screening

Background &amp; objective:Thyroid disorders are among the common endocrine problems during pregnancy with well-known adverse effects on both mother and fetus. Many of these adverse effects could be prevented or ameliorated by early detection and appropriate treatment of conditions, provided routine antenatal thyroid screening is done. Considering this view, the present study was aimed to find the prevalence of thyroid disorders and their spectrum in pregnancy in order to justify the necessity of routine antenatal thyroid screening.&#x0D; Methods: This cross-sectional study was conducted in the Department of Obstetrics &amp; Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period 1 year from July 2012 to June 2013 on pregnant women to screen for the thyroid disorders in pregnancy. Based on predefined eligibility criteria, a total of 246 pregnant women up to 36 weeks of gestation were consecutively included in the study. A short history with brief physical examination was done followed by collection of blood samples. Thyroid function was assessed by measuring serum levels of thyroid stimulating hormone (TSH). Serum free thyroxin (FT4) level was estimated in 71 cases, where TSH value was deranged. Trimester specific reference range of serum TSH was used to define hypothyroid, euthyroid and hyperthyroid cases. The suspected risk factors were then compared between abnormal and euthyroid groups to find their association with thyroid disorders.&#x0D; Result: The results of the study showed that the overall prevalence of abnormal thyroid function status was 30.9% (hypothyroidism 29.7% and hyperthyroidism 1.2%) based on normal range of serum TSH in different trimesters of pregnancy. Pregnant women with thyroid disorders were generally older than their euthyroid counterparts (p = 0.039). Hypothyroid state was fairly common with advancing gestation (21.3%, 30.3% and 34% in the 1st, 2nd, and 3rd, trimesters respectively). Pregnant women with personal or family history of thyroid disease in the past exhibited a higher prevalence of abnormal thyroid function than those who did not have such history (p = 0.041 and p = 0.044 respectively). Past menstrual irregularity, past history of subfertility or abortion were significantly associated with thyroid disorders (p = 0.042, p = 0.004 and p &lt; 0.001 respectively). Presence of goitre (21.1%) in current pregnancy also showed significant association with thyroid dysfunction (p = 0.001). The risk of developing abnormal thyroid function was observed to be 3.6(95% CI = 1.9 – 6.4) times higher in those who had at least one risk factor than those who did not have any risk factors (p &lt; 0.001). However, a sizable portion (27.6%) of pregnant women without any risk factors developed abnormal thyroid function.&#x0D; Conclusion: The study concluded that one in every three women may have thyroid disorder during pregnancy, primarily hypothyroidism. Adopting risk factor-based screening for thyroid disorders in pregnancy, there is every chance that a substantial number of cases with thyroid dysfunction may be missed. Therefore, routine antenatal thyroid screening is recommended.&#x0D; Ibrahim Card Med J 2020; 10 (1&amp;2): 74-83

A Thyroid Stimulating Hormone Reference Range: Iranian Thyroid Cohort study.

Background:Current reference values for thyroid function tests are derived from data from different ethnicities and geographical areas. In this article, we aim to select criteria from the guidelines proposed by the National Academy of Clinical Biochemistry (NACB) and to determine the TSH and T4 reference limits in the iodine-sufficient area of Isfahan, a metropolitan city in Iran.Materials and methods:This study was conducted within the framework of “Isfahan Thyroid Study (ITS)”, an ongoing prospective cohort that started in 2006 (n=2523) until 2011 (n=711) and included participants above the age of twenty. We measured TSH, total T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).Results:Recruitment was based on the NACB criteria, 1899 participants were included in 2006(58.5% male) and 377 in 2011(62.3% male). The mean± SD age was 39.66 ±12.71 and 48.96±12.35 years in 2006 and 2011, respectively. The mean± SD for TSH was 2.0±1.19 and 2.11±1.11 mU/L and T4 was 6.67±1.47 and 8.3±2.95 μg /dl in 2006 and 2011, respectively. In 2006, the 2.5th percentile of serum TSH levels was 0.4 mU/L (males: 0.4 mU/L, females: 0.5 mU/L) and the 97.5th percentile of serum TSH was 4.96 mU/L (males: 4.72 mU/L, females: 5. 3 mU/L). In 2011, the 2.5th percentile of serum TSH levels was 0.7 mU/L (males: 0.6 mU/L, females: 0.77 mU/L) and 97.5th percentiles of serum TSH was 4.9 mU/L (males: 5.7 mU/L, females: 5. 57 mU/L).Conclusion:This study determined age and sex specific TSH and T4 reference ranges in the Isfahanian population, which could theoretically enable clinicians to classify patients more accurately. (www.actabiomedica.it)

Urinary iodine in second trimester of pregnancy: A cross sectional study in tertiary care hospital of Belagavi

Background: Iodine is a nutritionally important trace element and its deficiency is a common health problem affecting a huge population, particularly pregnant women and children. The physiological role of iodine in the human body is synthesis of thyroid hormones. Thyroxine is approximately 60% iodine by weight. If iodine intake falls below approximately 100μg/day, Thyroid Stimulating Hormone (TSH) secretion is augmented, which increases plasma inorganic iodide clearance.&#x0D; Aims and Objective: To correlate urinary iodine with serum TSH in the second trimester of pregnant women.&#x0D; Material and Methods: One hundred five subjects were included in the study from tertiary care hospital. A random urine sample was collected. Iodine was estimated by ammonium persulfate method and TSH values were collected from the OBG department of the subjects enrolled. Statistics: Pearson correlation coefficient was done.&#x0D; Results: Median UI 138.50 (29.80-350.51) μg/L, median TSH 1.90(0.17-7.46) mIU/L. There was no significant correlation between UI and serum TSH with r = (0.0873, (p = 0.3756).&#x0D; Conclusion: Urinary iodine is a marker for population iodine status. A preferable biomarker is necessary to know the iodine status of individual which include not only nutritional biomarker and also required to organise reference range for TSH.

Associations between the levels of thyroid hormones and abdominal obesity in euthyroid post-menopausal women.

The aim of this study was to explore the association between thyroid hormones and abdominal fat quantities in euthyroid post-menopausal women. Serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) as well as body mass index (BMI) and waist circumference (WC) were collected from 540 euthyroid post menopausal women aged 45-65 years. Magnetic resonance imaging (MRI) was performed to measure visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area. Multivariate linear regression analysis was used to determine whether abdominal fat was associated with thyroid hormones. Weight, BMI, WC, fasting plasma glucose (FPG), fasting insulin (Fins), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), TSH, and fT4 were higher in the obese group than in the nonobese group (p < 0.05). The study participants were divided into four groups according to quartiles in the light of TSH reference range (0.1-4.2 mU/L). Subcutaneous adipose tissue and VAT increased with the TSH levels. Adjusted for age, years since menopause (YSM), BMI, and HOMA-IR, VAT was negatively correlated with fT4 and positively correlated with fT3 and fT3-to-fT4 ratio (fT3/fT4) (p < 0.05), while no association was found between SAT and thyroid hormones. Similarly, we found no relation between body fat distribution and TSH. Furthermore, the association of common indicators of obesity and thyroid hormones showed no significance. In euthyroid post-menopausal women, VAT rather than SAT was negatively correlated with fT4, and positively correlated with fT3 and fT3/fT4.

Subclinical hypothyroidism and metabolic syndrome: reasons for drug intervention

The high prevalence of metabolic syndrome (MS) and subclinical hypothyroidism (SHypo) creates danger of integral cardio-metabolic risk (CMR). A concept is being developed to increase thyroid-stimulating hormone (TSH) levels as a component of MS with the key role of insulin resistance (IR). To identify groups of active intervention, the definitions of SHypo with age and gender characteristics are analyzed. The results of randomized clinical trials showed a higher incidence of prediabetes and type 2 diabetes mellitus (T2DM) in SHypo, as well as positive associations of autoimmune thyroiditis (AIT) with components of MS, especially in postmenopausal women. The association of SHypo with a systemic inflammatory response is analyzed, which can determine an increase in cardio-metabolic risk. At the same time, most of the thyroid dysfunction and the components of MS are associated with insulin resistance.&#x0D; The feasibility of SHypo treating with levothyroxine is discussed: the threshold parameters of thyroid-stimulating hormone (TSH) are not determined for initiating treatment; in old age, due to a decrease in the need for thyroid hormones, an increase in the upper reference range of TSH is discussed; there is no evidence of a decrease in cardiovascular risk and mortality. In parallel, data have been accumulated on a decrease in TSH levels in overt and subclinical hypothyroidism in patients with MS and T2DM with metformin therapy. The gender effect of metformin on the activity of the hypothalamus-pituitary-thyroid axis was suggested, its new antihyperglycemic mechanism of action, including the activation of the AMP protein kinase (adenosine monophosphate (AMP) -activated protein kinase) in the pituitary gland, was revealed.&#x0D; It is possible that metformin is a promising therapeutic agent not only for patients with type 2 diabetes and thyroid disease, but also for MS and obesity. The multifaceted capabilities of metformin, including the correction of peripheral and central insulin resistance and a decrease in TSH levels in patients with SHypo, emphasizes an integrated approach to the prevention of CMR. The prolonged release form of metformin has several advantages: better tolerance, greater efficiency in the correction of IR, lipid and carbohydrate metabolism, additional indication - treatment of prediabetes, the possibility of prescribing for creatinine clearance up to 30 ml/min.

Levothyroxine prescribing and laboratory test use after a minor change in reference range for thyroid-stimulating hormone.

Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory. Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range. Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%-9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%-3.4%) to 9.1% (95% CI 9.0%-9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15-3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96-4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations (p < 0.001) and a total increase of 500 new prescriptions per month. Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges.

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.

Determining the TSH reference range in national newborn screening program for congenital hypothyroidism

Objective: Since the initiation of the thyroid screening program in Iran in 2005, 5 mIU/L has been selected as the threshold for thyroid stimulating hormone (TSH) for screening for congenital hypothyroidism. Given the specific disease pattern in the region and current controversies of the TSH cutoff point, a new cutoff point has been proposed in this study.Methods: This study was conducted on the existing database of the screening program consisting of 127,112 neonates in Markazi Province, center of Iran, during 2006–2012. Data on 614 referred neonates consisting of 414 neonates diagnosed of having hypothyroidism and 200 screened healthy neonates, were analyzed. The heel prick test had been done on the studied neonates to determine the TSH levels. The receiver-operator characteristic (ROC) curve and diagnostic values were used for data analysis.Results: The 5-mIU/L cutoff point in the study had a sensitivity and specificity and AUC of 86.5, 10 and 47%, respectively. Among the eleven selected cutoff points, 6.5 mIU/L had the appropriate sensitivity, specificity and AUC (58.9, 56.5 and 57%, respectively), negative and positive likelihood ratios (0.73 and 1.35, respectively).Conclusion: Given the very low specificity of the 5-mIU/L cutoff point for referral and with respect to the high rate of referrals and many false positive cases, we suggest to use the 6.5-mIU/L cutoff point which is more suitable.

The influence of different thyroid stimulating hormone cut-offs to diagnose subclinical hypothyroidism during the first trimester of pregnancy

Objective: To analyze the influence of different thyroid stimulating hormone (TSH) cut-offs to diagnose subclinical hypothyroidism (SCH) in the first trimester of gestation. Methods: A total of 896 pregnant women were enrolled in Peking University International Hospital between October 2016 and March 2018. Among them, 421 pregnant women with single fetus who were conformed to the criteria of National Academy of Clinical Biochemistry (NACB), without adverse pregnancy outcomes and obstetric complications, were selected to establish their self-sequential longitudinal reference ranges of thyroid function. Then, SCH was diagnosed in the first trimester, using different TSH cutoffs, such as the upper limit of the first trimester-specific reference range, 4.0 mU/L recommended by the 2017 Guidelines of American Thyroid Association (ATA), 5.17 mU/L (Roche reagent) recommended by 2012 Guidelines of Chinese Society of Endocrinology and Chinese Society of Perinatal Medicine, and 2.5 mU/L recommended by 2011 Guidelines of ATA, respectively. Results: The TSH reference range was 0.12-4.16 mU/L in the first trimester. Using TSH>4.16, 4.0, 5.17 and 2.5 mU/L to diagnose SCH in the first trimester, the prevalence rates were 4.35% (39/896), 5.92% (53/896), 1.56% (14/896) and 20.87% (187/896), respectively. There was no statistically significant difference between the prevalence rates of SCH using the TSH upper reference limit of 4.0 mU/L and 4.16 mU/L (P=0.134). When TSH was defined as>4.0 mU/L to diagnose SCH, the sensitivity, specificity and Youden index was 97.4%, 98.2%, and 0.956, respectively. Conclusions: The TSH upper reference limit of 4.0 mU/L recommended by 2017 Guidelines of ATA can be used as a cut-off to diagnose SCH in first trimester for the areas without trimester-specific reference ranges for TSH in China.

Trimester-specific reference ranges for thyroid hormones in pregnant women.

The aim of this study was to determine the trimester-specific reference range of thyroid function in Nanjing.A total of 805 pregnant women in the 1st, 2nd, and 3rd trimesters were recruited in the prospective, observational study during their routine antenatal clinic visit and 282 nonpregnant subjects served as controls. A questionnaire was completed by the subjects to record their personal health history, family history of thyroid disease, and consumption of estrogen or antithyroid drugs. Thyroid palpation was performed to exclude the thyroid goiter. Thyroid function and urine iodine were measured by chemiluminescence and arsenic cerium analysis.The trimester-specific reference ranges in Nanjing were as follows: thyroid-stimulating hormone (TSH) 0.02 to 3.78 mIU/L, free thyroxine (FT4) 13.93 to 26.49 pmol/L, total thyroxine (TT4) 103.39 to 319.43 nmol/L in the 1st trimester. TSH 0.47 to 3.89 mIU/L, FT4 12.33 to 19.33 pmol/L, TT4 92.28 to 234.88 nmol/L in the 2nd trimester. TSH 0.55 to 4.91 mIU/L, FT4 11.38 to 19.21 pmol/L, TT4 83.54 to 258.12 nmol/L in the 3rd trimester. According to the TSH reference range recommended by American Thyroid Association (ATA), the prevalence of subclinical hypothyroidism, subclinical hyperthyroidism, hyperthyroidism, hypothyroxinemia, and thyroid peroxidase antibody-positive were 12.42%, 0.50%, 0.99%, 1.61%, and 11.80%, respectively, prevalence according to the trimester-specific reference range were 1.99%, 0.25%, 1.61%, 0.37%, and 1.61%, respectively, which showed elevated hypothyroxinemia incidence and declined incidence of subclinical hypothyroidism and hyperthyroidism.Trimester-specific reference range varied from that of ATA's recommendation, influencing the diagnosis, and treatment of pregnant thyroid disorders. To detect and control these disorders properly, setting up trimester-specific reference is clinically essential.