Thyroid-stimulating Hormone Cutoff Research Articles

History of Neonatal Screening of Congenital Hypothyroidism in Portugal.

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country. Data were obtained from annual reports and from the national database of neonatal screening laboratory. The CH screening strategy primarily relies on the thyroid-stimulating hormone (TSH), followed by total thyroxine measurement as the second tier for confirmation. The TSH cutoff started at 90 mIU/L, decreasing to the actual 10 mIU/L. The coverage of the screening program has increased rapidly; although voluntary, it reached about 90% in 6 years and became universal in 10 years. Guideline and cutoff updates led to the identification of over 200 additional cases, resulting in specific retesting protocols for preterm and very-low-birth-weight babies. The actual decision tree considers CH when TSH levels are above 40 mIU/L. Data from the CH screening also provide an indication of the iodine status of the population, which is presently indicative of iodine insufficiency. The Portuguese neonatal screening for CH is a history of success. It has rapidly and continuously adapted to changes in knowledge and has become a universal voluntary practice within a few years.

Increased incidence of congenital hypothyroidism in China: An analysis of 119 million screened newborns.

Despite the lack of nationwide epidemiological studies, congenital hypothyroidism (CH) incidence in China has increased. We aimed to evaluate the trends of CH and the possible reasons behind them. Data from screened newborns from the Chinese Newborn Screening Information System from 2012 to 2019 was collected. We applied the Bayesian hierarchical Poisson regression model and meta-analysis to estimate incidence or proportion over the years. The estimated CH incidence increased from 4.01 per 10,000 births in 2012 to 5.77 per 10,000 births in 2019. The average annual growth rate (ARG) of CH incidence for all provinces varied from 0.59 to 20.96%. The most rapid rise in incidence was observed in cases with an initial thyroid stimulating hormone (TSH) concentration of < 10 mIU/L. The meta-analysis results showed that the proportion of permanent CH increased by 0.024% (95%CI: 0.011%, 0.037%) annually. Each 1 mIU/L decrease in TSH cutoff value was associated with a 2.96% increase in CH incidence. In the same period, the proportion of premature CH cases increased from 6.60 to 9.10%, which was much higher than the increase in preterm births. A significant relationship was not found between provincial growth rates in screening coverage and provincial baseline incidences of CH. Conclusion:CH incidence has substantially increased in China. The slight adjustment of the TSH cutoff value and increasing preterm birth rate contribute to such a trend; however, the contribution is limited. What is Known: • An uptrend in congenital hypothyroidism (CH) incidence has been reported in many European and American countries in the last two decades; however, no studies have been conducted in China to explain the increased CH incidence. • We provide a detailed epidemiological report on the trends of CH during 2012-2019 in China, with an attempt to explore the reasons behind it. What is New: • This first-ever national-wide epidemiological report in China showed an uptrend in CH incidence with variations over regions and CH subtypes. The mild lowering of TSH cutoff values and the increasing preterm birth rate contributed to this uptrend.

Limited Utility of Free Triiodothyronine Testing.

Free triiodothyronine (fT3) testing is most useful when thyroid stimulating hormone (TSH) is suppressed, and free thyroxine (fT4) is normal or decreased. These laboratory values in a symptomatic patient are referred to as T3 thyrotoxicosis. Standards for fT3 reflex testing have not been established. Herein, we examined the clinical utility of fT3 with the goal of identifying a TSH cutoff in the context of normal/decreased fT4 that maximizes the utility of measuring fT3. TSH, fT4, and fT3 results between January 2016 and October 2021 were extracted from the laboratory information system and grouped if resulted on the same day for the same patient. Frequency of biochemical T3 thyrotoxicosis was evaluated at different TSH cutoffs and in outpatient vs inpatient settings. Of the 4366 TSH-fT4-fT3 results, 70 (1.6%) were consistent with biochemical T3 thyrotoxicosis. The common reasons were previously diagnosed hyperthyroidism on antithyroid medication (n = 28) or hypothyroidism on thyroid medication (n = 18) and newly diagnosed hyperthyroidism (n = 20, 0.5%). The likelihood of detecting T3 thyrotoxicosis increased with lower TSH cutoff (<0.3 μIU/mL, 10.3% vs <0.0 1μIU/mL, 27.6%). All patients with newly diagnosed hyperthyroidism had TSH <0.01 μIU/mL. Higher frequency of T3 thyrotoxicosis was observed in the outpatient setting (34%) relative to the inpatient setting (14%, P < 0.001) when TSH < 0.01 μIU/mL. T3 thyrotoxicosis is a relatively rare diagnosis and fT3 measurement has limited utility in the vast majority of patients. A fT3 reflex for patients with TSH <0.01 μIU/mL and normal/low fT4 may improve clinical utility and reduce unnecessary testing, especially in the outpatient setting.

THE EFFECT OF LEVOTHYROXINE TREATMENT ON MATERNAL AND PERINATAL OUTCOMES IN PREGNANT WOMEN WITH SUBCLINICAL HYPOTHYROIDISM: A 5-YEAR RETROSPECTIVE STUDY AT A TERTIARY CARE HOSPITAL IN TURKEY

Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels with normal free thyroxine (fT4) levels. The aim of this study was to compare obstetric and neonatal outcomes in pregnant women with and without treatment for subclinical hypothyroidism. In this study, maternal and perinatal outcomes were evaluated in a total of 270 pregnant women who were diagnosed with subclinical hypothyroidism as a result of screening performed in three trimesters of pregnancy between 2015 and 2020 and followed up in our clinic, 149 of whom received levothyroxine treatment and 121 of whom did not receive treatment. Further, different cutoff values for TSH were compared. The rates of neonatal intensive care unit (NICU) requirement were not different according to the levothyroxine use status of the patients (p=0.73, p&amp;gt;0.05). Miscarriage rates did not differ according to levothyroxine use (p=0,87, p&amp;gt;0,05). TSH, T4 and antithyroid peroxidase levels did not differ according to the maternal use of levothyroxine (p&amp;gt;0,05). Birth weight, gestational week at birth, 1- and 5-minute APGAR scores, neonatal TSH and T4 levels did not differ according to the maternal use of levothyroxine (p&amp;gt;0,05). Among the adverse maternal and perinatal outcomes, the need for NICU admission and the rates of placental abruption, fetal distress, preterm premature rupture of membranes, preeclampsia, preterm labor, and small for gestational age were not significantly different among the TSH cutoff groups (p&amp;gt;0,05). The rate of premature rupture of membranes was higher in the group with TSH levels ≥2.5 mIU/L (p=0.04). Choosing 2.5 mIU/L as the cutoff value for TSH levels allows early diagnosis of subclinical hypothyroidism with a higher rate in pregnant Turkish women and proactive therapeutic management. Our study provides limited evidence for the success of levothyroxine therapy for adverse obstetric and neonatal outcomes.

Prevalence of congenital hypothyroidism in North Macedonia: data from a newborn screening program conducted for twenty years.

Congenital hypothyroidism (CH) is a common endocrine disorder that can be treated if timely detected by newborn screening, optimizing the developmental outcome in affected children. In the present study, we analyze the data of the national newborn thyroid screening program in North Macedonia collected over twenty years, including the CH prevalence as well as its geographical and ethnic variations. The thyroid-stimulating hormone (TSH) was measured on a filter paper blood spot sample using the DELFIA fluoroimmunometric assay. A TSH value of 15 mIU/L whole blood was used as the cutoff point until 2010 and 10 mIU/L thereafter. Out of 377,508 screened live births, a total of 226 newborns with primary CH were detected, providing an overall prevalence of 6.0 per 10,000. Lowering the TSH cutoff led to an apparently increased prevalence of the transient CH, from 0.2 to 2.4 per 10,000 live births (p < 0.0001) with an impact on the overall prevalence of primary CH (from 4.0 to 7.1 per 10,000, p=0.0001). Taking ethnicity into account, the significantly highest primary CH prevalence of 11.3 per 10,000 live births was observed among the Roma neonates, with a predominance of permanent CH (75.5%). There were also regional differences in the prevalence of primary CH. The highest primary CH prevalence of 11.7 per 10,000 live births was observed in the Vardar region, together with the highest regional prevalence of the transient CH (3.2 per 10,000). The highest prevalence of permanent CH was observed in the Pelagonia region (6.6 per 10,000) where the largest percentage of the Roma population lives. The overall CH prevalence is high in North Macedonia, with substantial ethnic and geographical variations. Further analysis to elucidate the causes for the significant variations in the CH prevalence including environmental factors is warranted.

Incidence and predictive factors of radiation‐induced hypothyroidism in breast cancer patients who receive supraclavicular lymph nodes irradiation: A prospective study

AbstractPurposeThis paper aimed to assess the incidence of radiotherapy‐induced hypothyroidism (RIHT) in breast cancer patients and correlate it with different factors.MethodsPatients with nonmetastatic breast cancer who received supraclavicular lymph node irradiation as a part of adjuvant radiotherapy from October 2019 to July 2020 were recruited and followed up for 18 months. All patients underwent three‐dimensional conformal radiotherapy and underwent computed tomography simulation. The levels of serum thyroid‐stimulating hormone (TSH), free triiodothyronine and free thyroxine levels were assessed at baseline (before starting radiotherapy) and 9,12, and 18 months after radiotherapy using immunochemilluminescence. Univariate and multivariate analyses were performed to identify significant factors associated with developing hypothyroidism.ResultsTwenty patients out of 96 (20.8%) developed hypothyroidism. Baseline TSH (cutoff value &gt;1.42 μIU/ml) was significantly correlated with hypothyroidism.ConclusionRoutine thyroid function tests assessment is recommended for all breast cancer patients at baseline and after radiotherapy.

Maternal hypothyroidism and adverse outcomes of pregnancy.

Hypothyroidism has been associated with pregnancy complications, but uncertainty prevail regarding the severity and the role of thyroid autoimmunity. This study aimed to evaluate adverse pregnancy outcomes by exposure to maternal hypothyroidism and thyroid autoimmunity. Retrospective cohort study. 14,744 singleton pregnancies from the North Denmark Region Pregnancy Cohort (2011-2015). Maternal thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) were retrospectively measured in early pregnancy blood samples (ADVIA Centaur XPT, Siemens Healthineers). Adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to estimate associations between maternal hypothyroidism (TSH cut-offs: 6.0 and 10 mIU/L), thyroid autoimmunity (TPO-Ab cut-off: 60 U/ml, Tg-Ab cut-off: 33 U/ml), and adverse pregnancy outcomes. Pregnancy outcomes were 93.2% live births, 6.5% spontaneous abortions, and 0.3% stillbirths. The frequency of spontaneous abortion was 6.5% when TSH was below 6.0 mIU/L, 6.5% when above 6.0 mIU/L (aOR 1.0 [95% CI: 0.5-2.0]), and 12.5% when above 10 mIU/L (aOR: 2.0 [95% CI: 0.8-5.2]). For outcome of preterm birth, the frequency was 5.4% when TSH was below 6.0 mIU/L, 7.8% when above 6.0 mIU/L (aOR 1.5 [95% CI: 0.7-2.9]), and 11.4% when above 10 mIU/L (aOR: 2.6 [95% CI: 0.9-7.3]). No association was found between thyroid autoantibodies and spontaneous abortion (TPO-Ab: aOR: 1.0 [0.8-1.3], Tg-Ab: 1.0 [0.8-1.2]) or preterm birth (TPO-Ab: aOR: 1.0 [0.8-1.2], Tg-Ab: 0.9 [0.7-1.2]). A high frequency of adverse pregnancy outcomes was seen among pregnancies exposed to maternal TSH above 10 mIU/L, whereas no association with thyroid autoantibodies was seen.

Screening for thyroid dysfunction with free T4 instead of thyroid stimulating hormone (TSH) improves efficiency in older adults in primary care.

Subclinical hypothyroidism (SCHT) is defined as a consistently elevated thyroid stimulating hormone (TSH) with a free T4 (fT4) within the reference range. This diagnosis may lead to additional monitoring, levothyroxine therapy and increased patient concerns, despite lack of evidence of treatment benefit in older adults. In order to avoid this diagnosis, we evaluated the efficiency of fT4-based screening for thyroid dysfunction, in older adults in primary care and compared it with TSH-based screening.Individuals aged >65years in primary care were selected for this retrospective study when both TSH and fT4 were individually requested irrespective of the TSH value. Exclusion criteria were C-reactive protein > 10 mg/l or a history of thyroid hormone monitoring in the previous year.Screening based on fT4 instead of TSH decreased reflex testing from 23.8% to 11.2%. The positive predictive value (PPV) for clinical hypothyroidism increased from 17.3% to 52.2%. The negative predictive value was 96.1% with TSH-based screening versus 97.8% with fT4-based screening. Elevation of the TSH cutoff value from 4.2 to 6.5 mU/l resulted in a reflex test percentage of 12.5% and a PPV of 31.0%.Our results suggest that screening for thyroid dysfunction in older individuals in primary care can be improved by screening based on fT4 instead of TSH or by adjusting the TSH cutoff value. Adjustment of the screening strategy may be of interest to health policy makers because of potential cost reduction. From a patient perspective, medical concerns and unnecessary biochemical follow-up might be reduced by circumventing the diagnosis SCHT.

Fifty years of newborn screening for congenital hypothyroidism: current status in Australasia and the case for harmonisation

Since its implementation 50 years ago in Quebec, Canada, newborn screening for congenital hypothyroidism has become one of the most successful public health measures worldwide. Screening programmes across Australia and New Zealand are characterised by significant commonalities in screening algorithms, and a high degree of regional cooperation in harmonisation efforts. We aimed to conduct a comprehensive survey of current performance and practices related to the total testing process for congenital hypothyroidism screening and provide recommendations for harmonisation priorities within our region. A survey was conducted involving the six newborn screening laboratories which provide complete geographic coverage across Australasia. Approximately 360,000 newborns are screened annually. Survey questions incorporated pre-analytical, analytical, and post-analytical aspects of the screening programmes and an extensive 5-year (2016-2020) retrospective analysis of individual programme performance data. Responses from individual screening programmes were collated. The uptake of newborn screening was over 98% for the six major jurisdictions. All programmes have adopted a single-tier thyroid stimulating hormone (TSH) strategy using the Perkin Elmer GSP instrument. Significant similarities exist between programmes for recommended age of collection and recollection protocols for low birthweight newborns. The process for the determination of TSH cutoffs varies between programmes. TSH lower cut-offs for borderline-positive and positive notifications between 12-15 and 12-25mIU/L blood, respectively. Recall rates vary between 0.08 and 0.20%. The case definition forcongenital hypothyroidism generally includes biochemical and radiological parameters in addition to the commencement of thyroxine. All programmes reported collecting biochemical and clinical data on infants with positive screening tests, and positive predictive values vary between 23.6 and 77.3%. Variation in reported incidence (1:1,300-2,000) cannot be entirely explained by cutoff or recall rate (although one programme reporting fewer cases includes only permanent disease). Despite similarities between newborn screening algorithms for congenital hypothyroidism across Australia and New Zealand, differences in reported programme performance provide the basis for further harmonisation. Surveillance of a large population offers the potential for the ongoing development of evidence-based screening guidelines.

Factors affecting recurrence in subacute granulomatous thyroiditis.

This study aimed to evaluate the factors affecting recurrence in subacute granulomatous thyroiditis (SAT). A total of 137 patients with SAT were enrolled in the study; 98 (71.5%) were women and 39 (28.5%) were men. The patients received either steroid or nonsteroidal anti-inflammatory drug (NSAID) for eight weeks. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (FT4), anti-thyroid peroxidase antibodies and thyroglobulin antibodies, neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio levels were evaluated. In addition, recurrence rates were compared between patients who received NSAID treatment and those who received steroid therapy. Treatment modality and pretreatment TSH, FT4, and ESR were significantly different between patients with and without recurrence (p = 0.011, 0.001, 0.004, and 0.026, respectively). Compared with patients without recurrence, those with recurrence had higher pretreatment TSH levels, but lower FT4 and ESR levels. On logistic regression analysis, treatment modality was found to be an independent risk factor for recurrence. The risk of recurrence was higher in those taking steroids than in those taking NSAIDs (p = 0.015). The optimal TSH cutoff value for recurrence was 0.045 µIU/mL, with a sensitivity of 83.3% and specificity of 76% (AUC 0.794, 95% CI 0.639-0.949). The risk of SAT recurrence was higher with steroid therapy than with NSAIDs. Patients who had mild thyrotoxicosis had relatively high recurrence rate and may need a relatively longer duration of treatment.

Estimating neonatal screening for congenital hypothyroidism test performance

Introduction: Newborn screening (NBS) is a system of organized search in the entire neonatal population for specific diseases. In Bosnia and Herzegovina, two diseases are included in NBS, congenital hypothyroidism (CH), and phenylketonuria. The screening for CH is based on determination of thyroid stimulating hormone (TSH) levels in blood obtained by heel prick method. The aim of this study is to evaluate the effectiveness of NBS program for CH based on TSH and establish the mean age of diagnosis of CH.Methods: TSH was measured by time-resolved fluoroimmunoassay (DELFIA Neonatal hTSH kit). The TSH cutoff value was 9 μU/mL. Neonates with TSH &lt; 9 μU/mL had a negative NBS result. Neonates with TSH ≥ 9 μU/mL were recalled for a confirmation test and thyroid hormones were determined from venous blood to establish diagnosis of CH.Results: A total of 24,351 neonates were subjected to NBS in our institution. A total of 164 newborns with TSH ≥ 9 μU/ml were sent to additional testing (mean recall rate of 0.68%) at a mean age of 11.4 ± 0.5 days of life. In this group, diagnosis of CH was confirmed in 22 neonates (13.41%). The mean rate of false positive results of NBS was 0.59%. The incidence of CH in Sarajevo Canton ranged from 1/2477 in 2018 to 1/641 in 2020. The mean incidence of CH over a 5-year period was 1/1085, while the mean age at the time of diagnosis was 16.5 ± 1.2 days.Conclusion: The analysis of NBS on congenital hypothyroidism data showed the satisfactory recall and false positive rate and indicated well selected TSH cutoff value. The mean age at the time of diagnosis assures early treatment and good neurological outcome in neonates with CH.

Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine.

Infants born preterm are affected by a hypothalamic-pituitary-thyroid axis that is immature and still developing as they progress closer to corrected term gestation. Multiple risk factors place preterm infants at risk for a hypothyroid state. However, there is variability in thyroid-stimulating hormone cutoff values and limited data on free thyroxine reference intervals to guide clinicians. 1584 thyroid-stimulating hormone and 1576 free thyroxine laboratory samples that were originally collected to screen hospitalized infants for delayed-onset of hypothyroidism were retrospectively evaluated from a group of 1087 infants who ranged in postmenstrual age from 25 to 43 weeks gestation at the time of laboratory sample collection. Median thyroid hormone values and reference intervals were established using R and the mixtools package. Thyroid-stimulating hormone reference intervals remained similar across gestational ages from 0.340-9.681 µIU/mL in 25-27 6/7-week infants to 1.090-7.627 µIU/mL in 40-43-weeks infants. For the same age groups, free thyroxine reference intervals increased from 0.42-0.91 ng/dL to 0.87-1.32 ng/dL. The reference intervals identified suggest that infants <31 weeks gestation have a higher thyroid-stimulating hormone and lower free thyroxine level at baseline than previously anticipated. The increasing free thyroxine values in preterm to term infants indicate a maturing hypothalamic-pituitary-thyroid axis. Clinicians need thyroid hormone reference intervals that also vary by postmenstrual age to aid the evaluation of sick preterm infants who are at risk of a delayed hypothyroidism diagnosis that can be missed on the initial newborn screen. This study provides one of the largest samples of thyroid-stimulating hormone and free thyroxine data to establish reference intervals in preterm infants. Clinicians may utilize the identified postmenstrual age-based reference intervals to inform follow-up thyroid testing in preterm infants at several weeks postnatal age.

Utility of Repeat Testing for Congenital Hypothyroidism in Infants with Very Low Birth Weight

To assess for possible missed hypothyroidism in infants of very low birth weight (VLBW) whose initial newborn screening (NBS) was within normal reference range. We analyzed serum thyroid-stimulating hormone (TSH) obtained at 36weeks of corrected gestational age or at hospital discharge if earlier (retest TSH) in infants with VLBW in the neonatal intensive care unit to determine the prevalence and factors associated with retest TSH ≥5 mU/L, a concentration requiring close follow-up for hypothyroidism. Utility of alternative cut-offs for NBS TSH also was assessed. A total of 398 infants, median gestational age 29 (range 22-36) weeks, birth weight 1138 (470-1498) g, were included in this study. Retest TSH was obtained at 49.5 (12-137) days after birth. Median retest TSH was 3.1 (0.5-27.9) mU/L. Seventy-three (18.3%) of the cohort had retest TSH ≥5 mU/L. Adjusting NBS cut-off to ≥15 or ≥10 mU/L identified <50% of infants with TSH ≥5 mU/L, resulting in 6% false positives and >70% false negatives. Multiple regression modeling indicated that 35% of variance in retest TSH value was explained by NBS TSH concentration, birth weight, and gestational age, all P<.01. Retesting for hypothyroidism at 36weeks of corrected gestational age in infants with VLBL and normal NBS could identify infants who require ongoing surveillance until thyroid function has been definitively ascertained. Adjusting NBS TSH cutoffs is not a valid option for identifying potential hypothyroidism in infants with VLBW because of lack of sensitivity and unacceptable false-positive and false-negative rates.

Optimizing Cord Blood Thyroid Stimulating Hormone Cutoff for Screening of Congenital Hypothyroidism-Experience from Screening 164,000 Newborns in a Tertiary Hospital in India.

Background and Objectives:In our institution, we have an ongoing newborn thyroid screening (NBS) program since July 2001. In the initial 9 months, we used cord blood thyroid-stimulating hormone (TSH) (CBTSH) cutoff of 20 mIU/L and thereafter the cutoff was increased to 25 mIU/L. Our objective was to evaluate whether a CBTSH cutoff of 25 mIU/L is sensitive and cost-effective in NBS of congenital hypothyroidism (CH).Materials and Methods:All in-born babies are screened and those with CBTSH ≥25 mIU/L are recalled for confirmatory TSH/T4/FT4 tests. CH is confirmed with elevated TSH and low T4/FT4. Those with CBTSH 20–24.99 mIU/L were recalled for confirmatory tests in initial period of our NBS and prospectively between January and August 2017. Statistical analysis was done to derive positive predictive value and sensitivity to diagnose CH for each CBTSH between 20 and 30 mIU/L.Results:A total of 164,163 neonates were screened from July 2001 to August 2017. Of the 2352 babies with CBTSH ≥25–30 mIU/L, 1763 returned for retesting and 5 confirmed as CH (4 gland-in-situ and 1 absent uptake on nuclear scan). Of the 14,742 screened during the study period, 195 of the 293 babies with CBTSH 20–24.99 mIU/L returned for retesting and none diagnosed as CH. A CBTSH of 25 mIU/L has 99.2% sensitivity and 97.5% specificity. A lower screen TSH cutoff 20 mIU/L would result in recall of additional 300 babies/year with no definite improvement in sensitivity.Conclusions:Our data justify the continuation of using screen TSH cutoff of 25 mIU/L while using cord blood for NBS in our population. With a diverse and large population, it is important that we use feasible regional screen cutoffs for optimal use of our resources.

Spectrum of thyroid dysfunction and dementia: a dose-response meta-analysis of 344,248 individuals from cohort studies.

Thyroid hormone, as a modifiable risk factor for dementia, promotes neurocognitive function and regulates metabolic processes. Various studies have defined different thyroid-stimulating hormone cutoffs, but the safest thyroid-stimulating hormone concentration was absent. A dose–response meta-analysis describing the overall functional relation and identifying exposure intervals associated with a higher or lower disease risk is thus desirable. Therefore, our current analysis was conducted to understand the influence of thyroid dysfunction on dementia risk. We searched PubMed, Embase, and Web of Science before May 1, 2020 for human studies published in English. Studies were considered for inclusion if they used a cohort study design to measure the risk of dementia in different thyroid function status groups, diagnosed thyroid functional status and all-cause dementia, included participants aged >18 years, and provided quantitative measures of data. The analysis contained 17 articles with 344,248 individuals with a 7.8-year mean follow-up. Ten studies with 329,287 participants indicated that only subclinical hyperthyroidism was associated with an increased risk of dementia. In contrast, subclinical hypothyroidism, clinical hyperthyroidism, and clinical hypothyroidism did not affect dementia. In the dose–response meta-analysis with 46,417 samples from 11 studies, the association of thyroid-stimulating hormone with the risk of dementia exhibited a U-shaped curve. Our study indicated that subclinical hyperthyroidism was associated with the risk of dementia and the thyroid-stimulating hormone concentration at around 1.55–1.60 mU/L as the optimum range for the risk of dementia.

The Prevalence of Thyroid Dysfunction and Autoimmunity in Women With History of Miscarriage or Subfertility.

To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. Observational cohort study. A total of 49 hospitals across the United Kingdom between 2011 and 2016. Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. None. Rates of thyroid dysfunction. Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.

SCREENING FOR CONGENITAL HYPOTHYROIDISM AND THE ASSOCIATION OF CONGENITAL HYPOTHYROIDISM WITH SCREENING THYROID-STIMULATING HORMONE LEVELS OF 10–20 MIU/L AMONG INBORN NEONATES IN A GOVERNMENT TERTIARY CARE HOSPITAL OF NORTH KERALA

Background: Newborn screening for hypothyroidism is necessary because of the high incidence of congenital hypothyroidism (CH) in various studies. The necessity of doing confirmatory tests with screening thyroid-stimulating hormone (TSH) levels as low as 10 mIU/L is still unclear. Objectives: To find out the incidence of CH as well as its association with screening TSH levels between 10 and 20 mIU/L. Materials and Methods: In a prospective observational study, inborn neonates irrespective of their gestational age were enrolled and screened for CH using venous TSH levels. Those with TSH levels ?10 mIU/L were subjected to confirmatory tests (free T4 and TSH levels) for the diagnosis based on the recommendations of the Indian Society for Pediatric and Adolescent Endocrinology. The various characteristics of the neonates such as birth weight, gender, gestational age, and maternal thyroid status were recorded and their relationship with subsequent CH was studied. The association between screening TSH levels 10–20 mIU/L and CH was also analyzed, and the cutoff point for screening TSH was determined using receiver operated characteristic (ROC) curve. Results: A total of 2407 neonates were screened for CH, out of which 357 (14.8%) were retested with free T4 and serum TSH levels. The incidence of CH was 1 in 160.5 (6.2/1000 live births). The male to female ratio was 1.5:1. There was a significant association between screening TSH levels and CH. A total of 0.6% of neonates diagnosed with CH had screening TSH levels in the range of 10–20 mIU/L, but this association was not found to be statistically significant, and the ideal cutoff value was 19.45 mIU/L based on ROC curve. Conclusion: The incidence of CH is high which upholds the need for universal newbornthyroid screening. Although there is no statistically significant association between CH and screening TSH levels 10–20 mIU/L, a few cases are likely to be missed on using a higher screening TSH cutoff value of 20 mIU/L.

Thyroid-Stimulating Hormone Reference Ranges for Preterm Infants.

Many newborn screening (NBS) programs now perform repeat or serial NBS to detect congenital hypothyroidism. There is wide variation in thyroid-stimulating hormone (TSH) cutoffs used by NBS programs. Data on TSH reference ranges in preterm infants at increasing postnatal age are limited. Our study objective was to determine TSH reference ranges for preterm infants born at <32 weeks' gestation. We analyzed serial TSH levels on NBS performed on infants born between 22 and 31 weeks' gestation from 2012 to 2016 in Wisconsin. The study cohort was divided into 2 groups (22-27 and 28-31 weeks), and TSH percentiles were defined from birth to the term equivalent gestational age. The study cohort consisted of 1022 and 2115 infants born at 22 to 27 and 28 to 31 weeks' gestation, respectively. The 95th percentile TSH level for the group born at 22 to 27 weeks' gestation gradually decreased and reached a nadir at ∼10 to 11 weeks. In contrast, for the group born at 28 to 31 weeks' gestation, the 95th percentile TSH level reached a nadir at ∼5 to 6 weeks. At 3 to 4 weeks after birth, the 95th percentile TSH level ranged from 11 to 11.8 μIU/mL for the group born at 22 to 27 weeks' gestation and ranged from 8.2 to 9 μIU/mL for the group born at 28 to 31 weeks' gestation. Using a statewide cohort of preterm infants, we constructed TSH reference charts from birth to the term equivalent gestation for preterm infants born at <32 weeks' gestation. Use of a single cutoff for all preterm infants might lead to misdiagnosis. The differences in TSH levels according to gestational-age categories might explain the increased frequency in congenital hypothyroidism diagnoses among preterm infants. These data are useful for defining age-adjusted NBS TSH cutoffs for preterm infants.

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.