Thyroid-stimulating Hormone Threshold Research Articles

What is the ideal thyroid-stimulating hormone (TSH) threshold value in congenital hypothyroidism screening? Twin study.

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Therefore, the majority of developed countries have aimed to diagnose cases early through screening programs. In these screening programs, levels of thyroid-stimulating hormone (TSH) and free thyroxine are examined in dried blood spots taken between days 3 and 5 of life. While many countries accept TSH threshold value of 8 mU/L, there is still no consensus on the ideal TSH threshold value. As no twin studies on the TSH threshold value have been conducted previously, this study was planned. Eight pairs of twins were included in the study, with one of the twins having plasma TSH value ≥8 mU/L and the other <8 mU/L, measured between days 3 and 5 of life. The study aimed to investigate whether determining threshold TSH value of 8 mU/L would be beneficial by comparing somatic growth, mental development, and neuromotor development between twins. The age, gender, gestational weeks, birth weights, height, weight, and initial TSH values taken between days 3 and 5 of all cases were recorded. The patients' plasma Vitamin B12, folate, 25-OH Vitamin D, ferritin, and hemoglobin levels were measured. After that, they were evaluated by a child and adolescent psychiatry. Finally, the Denver Developmental Test was applied to the cases. There was no significant impairment in somatic growth, mental development, and neuromotor development in the long-term outcomes of cases with plasma TSH ≥ 8 mU/L compared to those with plasma TSH < 8 mU/L among the twins participating in our study.

Polycystic Ovary Morphology, Subclinical Hypothyroidism, and the Cutoff Value of Thyroid-Stimulating Hormone, a Population-Based Study.

Although numerous studies have explored the link between polycystic ovary syndrome (PCOS) and thyroid dysfunction, the relationship between polycystic ovary morphology (PCOM) and thyroid issues remains unclear. This study aimed to examine the association between PCOM and subclinical hypothyroidism (SCH) as well as the threshold for thyroid-stimulating hormone (TSH). Data were drawn from the Iranian PCOS prevalence study and the Khuzestan PCOS prevalence study. Eligible participants were divided into two groups: those with PCOM (n = 120) and a control group (n = 630). A logistic regression model was employed to assess the impact of PCOM on SCH, with odds ratios and 95% confidence intervals calculated. Additionally, a quantile regression model was used to evaluate the effect of PCOS on TSH levels. The results indicated no significant association between PCOM and SCH (adjusted OR: 1.38, 95% CI: 0.80-2.37; p = 0.243). Furthermore, after adjusting for confounding factors such as age, body mass index (BMI), and number of pregnancies, no significant differences were found in TSH levels between the PCOM and control groups. The prevalence of SCH and the TSH threshold were similar in both groups. Further comprehensive population-based studies with detailed thyroid evaluations are recommended.

Analysis of risk factors for papillary thyroid carcinoma and the association with thyroid function indicators.

This study aims to analyze the relationship between papillary thyroid carcinoma (PTC) and various factors. The study involved two groups-PTC patients and non-PTC controls. We utilized binary logistic regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression for variable selection and risk factor analysis. Correlation analysis was performed using Spearman's rank correlation. The diagnostic value of thyroid stimulating hormone (TSH) levels for PTC was assessed using Receiver Operating Characteristic (ROC) curves. PTC patients exhibited higher body mass index (BMI) (23.71 vs. 22.66, p<0.05) and TSH levels (3.38 vs. 1.59, p<0.05). Urinary iodine concentration (UIC) was an independent predictor of PTC (OR=1.005, p<0.05). The optimal TSH threshold for PTC diagnosis was 2.4 mIU/L [The Area Under the Curve (AUC)=67.3%, specificity=71.4%, sensitivity=70.1%]. TSH levels positively correlated with BMI (r=0.593, p<0.05) and UIC (r=0.737, p<0.05). UIC may be an independent predictor of PTC, and TSH levels have some diagnostic value for identifying PTC.

A practical gestational age-based algorithm for timely detection of hypothyroidism in premature infants.

To assess utility and accuracy of a gestational age-based screening targeting premature infants to detect congenital hypothyroidism. A prospective cohort study was conducted in infants <35 weeks' gestational age with clinical outcomes at 2-3 years of age. Patients received newborn screenings at 24 hours and 10-14 days of life. Free T4 (FT4) and thyroid-stimulating hormone (TSH) levels were measured at one month of life and repeated based on algorithm by corrected gestational age. Among infants <35 weeks gestation (n = 938), the incidence of hypothyroidism requiring treatment was 1:58. TSH levels at one month of age was predictive of treatment (AUC 0.96, 95% CI 0.88-1). The optimal TSH threshold of 8 mIU/L (8 µU/ml) increased the specificity to 0.97 and sensitivity to 0.88. Following initiation of treatment forhypothyroidism during NICU hospitalization,43.8% (n = 7) were diagnosed with permanent congenital hypothyroidism. Our study supports a gestational age-based screening algorithm for early detection of hypothyroidism in premature infants.

In infertile women with subclinical hypothyroidism, with or without thyroid peroxidase antibodies, serum TSH during pregnancy follows preconception values and thyroid hormones remain stable.

How does subclinical hypothyroidism, defined in infertile women during preconception by thyroid-stimulating hormone (TSH) >2.5 or >4.5 mIU/l, with or without thyroid peroxidase antibodies (anti-TPO) >100 IU/ml, impact thyroid hormone levels during pregnancy and after birth? During pregnancy, TSH levels remain similar to those in preconception, even with supplementary thyroxine, whereas the serum levels of anti-TPO progressively decline. Overt hypothyroidism impacts both pregnancy and offspring but randomized clinical trials and cohort studies failed to detect the benefit of treatment with thyroxine in cases with low-threshold TSH or with anti-TPO during pregnancy. First, the prevalence and reproducibility of two candidate cut-off levels of subclinical hypothyroidism in a cohort of 177 infertile women was compared with 171 women not aiming for pregnancy. Second, the impact of distinct setpoints of TSH in preconception (with or without anti-TPO) was monitored during pregnancy in 87 previously infertile women by high-frequency monitoring of thyroid function. Both studies were carried out from 2007 to 2019. Reproducibility and prevalence of subclinical hypothyroidism were examined in infertile women presenting in the fertility care unit of an academic institution. Women not aiming for pregnancy participated as controls. In both groups, TSH and anti-TPO were measured two times on different occasions. In addition, a group of previously infertile women with known preconception setpoints of TSH (with or without anti-TPO) were followed up prospectively throughout pregnancy and after birth. During pregnancy, serum was sampled weekly until Week 12, then monthly until delivery, and once after birth. Only cases with preconception TSH >4.5 mIU/l were supplemented with thyroxine. After collection of all samples, the serum levels of anti-TPO and the major thyroid hormones were measured. Prolactin with known fluctuations during pregnancy was used as reference. Measures of both TSH and anti-TPO at two different time points were accurate and reproducible. The odds of subclinical hypothyroidism in infertile women and controls were similar. During pregnancy, TSH closely followed preconception TSH levels, whereas serum levels of the thyroid hormones predominantly remained within or above (not below) the reference. Treatment of infertile women with preconception TSH >4.5 mIU/l with thyroxine resulted in higher free thyroxine (fT4) serum levels. The serum levels of anti-TPO declined as pregnancies evolved. The numbers of participants both in the prevalence study and in pregnancy did not reach the a priori estimated numbers. For ethical reasons, the patients with preconception TSH >4.5 mIU/l were treated with thyroxine. The findings apply to infertile women only. We propose to use >4.5 mIU/l as the serum TSH threshold for supplementing women with thyroxine before pregnancy. During pregnancy, fT4 may be the better marker to monitor thyroid function. The consistent decrease of anti-TPO antibody levels during ongoing pregnancies must be considered a protective element. The prevalence part of this study was supported by Merck-Serono, Geneva (TH006/EMR200007-603). The hormone measurements of the serum samples collected during the follow-up pregnancies were made possible by financial support of Roche Diagnostica (November 1721, 2017, Rotkreuz, Switzerland). I.D.G. was supported by a grant of the Repronatal Foundation, Basel, Switzerland. All authors declare no conflict of interest. Research Database of UniBasel, project no. 576691 (2007).

Subclinical Hypothyroidism Diagnosis and Management in Primary Care settings

Subclinical hypothyroidism is a prevalent thyroid disorder characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free thyroxine (T4) levels. Its diagnosis and management in primary care settings present ongoing challenges and uncertainties. This systematic review aims to evaluate the current evidence regarding the diagnosis and management of subclinical hypothyroidism in primary care, with a focus on diagnostic criteria, clinical outcomes, and treatment approaches. A comprehensive search of electronic databases (PubMed, Embase, Cochrane Library) was conducted to identify relevant studies published in English within the last 10 years. Randomized controlled trials, cohort studies, and systematic reviews were included. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The findings were synthesized descriptively, and meta-analysis was conducted when appropriate. A total of 25 studies met the inclusion criteria and were included in this review. Diagnostic criteria for subclinical hypothyroidism varied across the studies, with differing TSH thresholds used to define the condition. The clinical outcomes associated with subclinical hypothyroidism were heterogeneous, including cardiovascular risks, metabolic disorders, and quality of life. The management of subclinical hypothyroidism in primary care was diverse, ranging from watchful waiting to levothyroxine therapy. The benefits of levothyroxine treatment were inconclusive, with some studies reporting improvement in symptoms and lipid profiles, while others found no significant differences compared to placebo or observation. The diagnosis and management of subclinical hypothyroidism in primary care remain controversial. The variability in diagnostic criteria and inconsistent evidence on clinical outcomes and treatment efficacy complicate decision-making. Future research should focus on establishing standardized diagnostic thresholds, evaluating ....

The Correlation between the First Trimester Combined Test Results and Thyroid Stimulating Hormone Levels as Well as Its Effect on Pregnancy Outcomes.

Determining the pregnancy outcomes with independent prognostic factors in the first trimester combined screening test and thyroid stimulating hormone (TSH) is a concern for practitioners. We aimed to evaluate the correlation between TSH and first trimester combined screening test levels and examine their effects on pregnancy outcomes in healthy pregnant women. A total of 349 pregnant women in Izmir Ataturk Training and Research Hospital, Turkey with normal TSH values in the first trimester between 2015 and 2020 were enrolled. Patients were divided into two groups as 274 and 75 patients according to TSH values with 2,5 as cut-off value; their birth weights and weeks were compared. Patients were also divided into three groups according to gestational weeks; their TSH values and combined tests were compared. When grouped based on the TSH threshold value (2.5uIU/ml), no significant relationship was found between the combined test parameters and TSH levels. In the combined test, after grouping according to the week of gestation, a negative correlation was observed between free beta-human chorionic gonadotropin (β-hCG) and TSH measured at 11 weeks (P=0.040, r=-0.189). A significant negative correlation was found between free β-hCG and newborn birth weight (P=0.032, r=-0.199), TSH and delivery time (P=0.011, r=-0.235). Free β-hCG and TSH levels could guide practitioners for birth weight and early delivery, respectively. Postponing the combined test for patients with elevated serum TSH levels to between the 12th and 13th weeks of gestation may reduce false positives.

Management of childhood cancer survivors at risk for thyroid function abnormalities: A Delphi study.

Thyroid function abnormalities can occur after treatment for childhood cancer. Evidence for the management of thyroid dysfunction among asymptomatic childhood cancer survivors (CCS) is lacking. We used a Delphi consensus methodology to expand guidelines for screening asymptomatic CCS at risk for thyroid dysfunction and explore recommendations for the clinical management of abnormal results. A Delphi panel of 40 expert physicians representing oncology, endocrinology, and primary care participated in three rounds of anonymous, iterative questionnaires formatted as clinical scenarios. Consensus is defined as ≥ 90% of panelists agree with recommendation and disagreement as < 70% agree. Panelists reached consensus that CCS treated with radiation including neck, total body, whole brain, brain including the hypothalamic-pituitary axis (HPA), and therapeutic meta-iodobenzylguanidine (MIBG) should have annual, lifelong screening using serum thyroid-stimulating hormone (TSH) and free T4 starting within one year off-treatment (98%). Panelists disagreed on continuing to screen CCS for thyroid dysfunction after immunotherapy associated with acute thyroid injury (31%-50%). There was also disagreement on indications for brain (17%-43%) or thyroid (50%-65%) imaging, laboratory tests to assess the HPA (29%-75%), and TSH threshold to initiate treatment of subclinical hypothyroidism. Lack of evidence was the most frequent rationale panelists offered for not recommending additional testing or medications. Panelists' recommendations did not vary by geography, specialty, or survivorship clinical experience. Consensus was reached on most recommendations for screening and management of cancer treatment-related thyroid dysfunction. Screening after completion of thyroid-toxic immunotherapy, indications for imaging, and treatment of subclinical hypothyroidism are areas of disagreement for further investigation.

The relationship between TSH levels and clinical pregnancy outcomes for patients who undergo in vitro fertilization/intracytoplasmic sperm injection: a retrospective study.

BackgroundThyroid dysfunction is linked with adverse pregnancy outcomes, an upper limit of a normal thyroid-stimulating hormone (TSH) threshold of 4.12–4.5 mIU/L should be considered for subclinical hypothyroidism in the infertile female population. Whereas, it’s controversial whether or not the infertility thresholds for upper limit of TSH threshold of 2.5 mIU/L. In our study examines the correlation of optimal TSH levels and clinical pregnancy outcomes after fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) embryo transfer cycles.MethodsPatients who underwent fresh IVF/ICSI embryo transfer cycles for the first time who presented between January 1, 2015 and December 31, 2017 at the Chongqing Institute of Reproductive and Genetic, Chongqing Health Center for Women and Children were enrolled. We excluded patients with ≥40 years, body mass index (BMI) ≤18 or ≥28 kg/m2, the man with severe oligoasthenospermia, women with poor ovarian reserve, and presence of endocrine disorders, uterine anomaly, sactosalpinx, abnormal thyroid function, preimplantation genetic diagnosis, and chromosomal abnormality or polymorphism. Baseline characteristics and clinical pregnancy outcomes were observed in our study. We detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by Receiver operating characteristic (ROC) curves and logical regression.ResultsA total of 6,088 patients who undergo IVF/ICSI were included. We first detected that the live birth rate had a statistically significant difference when the TSH level was 3 mIU/L. With the TSH ≤3 mIU/L group having a higher live birth rate than the TSH >3 mIU/L group (51.79% vs. 47.89%, P=0.024), meanwhile no significant difference were revealed between the early miscarriage rate (12.54% vs. 14.97%, P=0.091) and early clinical pregnancy rate (59.21% vs. 56.32%, P=0.114). There were no differences in pregnancy outcomes when the TSH threshold was at 3.5 or 4 mIU/L and no association was detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by ROC curves and logical regression.ConclusionsPatients undergoing IVF/ICSI with a serum TSH level ≤3 mIU/L may have a higher live birth rate rather than ≤2.5 or ≤4 mIU/L.

Risk of over- and under- treatment with levothyroxine in primary care in Copenhagen, Denmark.

A decrease over time in thyroid stimulating hormone (TSH) levels when initiating levothyroxine (L-T4) therapy for hypothyroidism has been reported, where treatment most often is initiated with TSH levels below 10 mIU/L. The primary objective of this study was to investigate whether this lower TSH threshold resulted in an increased number of overtreated patients. Retrospective cohort study comprising inhabitants in Copenhagen had TSH measurements requested by general practitioners which led to a new prescription of L-T4 between 2001 and 2012. Over- and under- treatment were defined as TSH <0.1 mIU/L or above 10 mIU/mL, respectively, in three consecutive measurements. Data were analyzed by Aalen-Johansen estimators and Cox proportional hazards models. In total, 14 533 initiations of L-T4 were included in the study. The cumulative risk of being over- or undertreated was 4.7 and 7.4% after 10 years. The hazard of overtreatment was higher among women, younger adults, and with lower initial TSH levels. The hazard of overtreatment decreased over the time period from 2001 to 2012. Among overtreated individuals, the chance of returning to a normal TSH was about 55% after 10 years. In 18% of the cases, L-T4 therapy was initiated on TSH levels less than 5 mIU/L. Although a still decreasing threshold for initiating L-T4 therapy is known, the risk of overtreatment (and undertreatment) was low and lessened in the period 2001-2012 among Danish primary care patients. Nevertheless, as many as 18% were started on L-T4 with normal TSH levels.

Patterns of Thyroid Hormone Prescription in Patients with Bipolar or Schizoaffective Disorder: Findings from the LiSIE Retrospective Cohort Study.

The prescription of thyroid hormone replacement therapy (THRT) has increased in the general population; the thyroid stimulating hormone (TSH) threshold to initiate THRT has decreased. It remains unclear whether a similar trend has occurred in patients with bipolar disorder (BD). In this work we explore patterns and trends of prescribing THRT in patients with BD or schizoaffective disorder (SZD) with an observational study and time-trend analysis in the framework of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. In most patients, THRT was initiated for subclinical hypothyroidism. The median TSH at which THRT was started was 6.0 (IQR 4.0) mIU/L and the median free serum thyroxine (fT4) at which THRT was started was 11.8 (IQR 3.9) pmol/L. The median TSH concentration at the start of THRT decreased annually with 0.10 mIU/L (p = 0.047) and was higher in patients treated with lithium than in patients treated with other mood stabilisers (p = 0.02). In conclusion, THRT was typically initiated in the context of mild or absent alterations of thyroid function tests with a decreasing TSH threshold. As THRT is rarely reversed once initiated, clinicians need to weigh up potential benefits and risks when prescribing THRT for subclinical hypothyroidism in patients with BD or SZD.

Effectiveness of Different Thyroid Stimulating Hormone Thresholds for Thyroid Hormone Withdrawal - Aided Radioiodine Ablation in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta - Analysis

Background: Patients with differentiated thyroid cancer (DTC) may benefit of radioiodine ablation (RAI) to reduce the probability of thyroid cancer recurrence. Guidelines recommend that thyroid stimulating hormone (TSH) of >30mIU/L before RAI to optimize treatment response. However, evidence regarding this recommendation is conflicting. We conducted a systematic review and meta-analysis to compare outcomes (thyroid cancer recurrence and survival at 10 years of follow up) of stimulated TSH threshold before RAI with primary analysis focus on <30 mIU/L versus ≥30 mIU/L, and subgroup analysis on <90 mIU/L versus ≥90 mIU/L in patients with DTC after initial total thyroidectomy. Methods: The protocol for this study is registered and available online (CRD42020158354). Briefly, we searched several databases from their inception to April 2020. Reviewers, working independently and in duplicate selected studies for inclusion, extracted data, and evaluated each study’s risk of bias. We excluded studies that used recombinant human thyroid stimulating hormone before ablation. Results: We included five retrospective cohort studies, which enrolled a total of 2,514 patients. Risk of bias was low in four studies and high in one study. Mean age was 47 years old (ranged from 40.7 to 47.9) and most of them were female (69%). The most common DTC type was papillary thyroid cancer (78%). From those articles that reported tumor characteristics, 48% had a size ≤2cm (T1b) and 47% >2cm. Moreover, 73% of the patients had no regional lymph metastasis (N0). Two studies reported radioiodine mean dose given of 30 and 100 mci. A total of 301 patients were included in the TSH threshold <30 mIU/L group and 1788 patients in the TSH ≥30 mIU/L group. Comparing stimulated TSH threshold before RAI (<30 mIU/L versus ≥30 mIU/L), there was difference in recurrence at 1 year (RR 2.46 (C.I. 1.09-5.55) and at 20 years (RR 1.71 (C.I. 1.19 – 2.47). However, there was no difference in mortality at 20 years (RR 0.53 (Confidence Interval (C.I.) 0.12-2.23). In addition, 10-years recurrence was not different when we compared <90 mIU/L versus ≥90 mIU/L TSH (RR 1.06; 95%CI: 0.88 – 1.27). Conclusions: Mortality do not differ between recommended TSH goal (≥30 mIU/L) vs <30 mIU/L in thyroid hormone withdrawal-aided radioiodine ablation in DTC patients. However, the risk of recurrence is reduced when patients achieved a TSH level >30 UI/mL. These results suggest that patients may need to reach a stimulated TSH ≥30 mIU/L stimulated TSH threshold to be treated. Randomized trials are needed to confirm these findings.

Thyroid hormone therapy in old age

There is evidence that the treatment of overt hyperthyroidism with thyroid hormones is able to reduce mortality as well as cardiovascular and musculoskeletal morbidity. It remains unclear whether these data can be extrapolated to the mildest form of hypothyroidism, subclinical hypothyroidism. Furthermore, it is uncertain whether and to what extent the threshold for therapeutic intervention needs to be modified in the elderly, in whom hypothalamo-pituitary regulation is increasingly insensitive to the negative feedback by thyroid hormones and the patients' response to thyroid hormones changes. The aim of this review is to evaluate the current evidence on the treatment of hypothyroidism in old age with regard to the initiation of therapy and the therapeutic goals. According to new original data and meta-analyses, therapy with thyroid hormones does not alter morbidity and mortality in patients with subclinical hypothyroidism with thyroid stimulating hormone (TSH) below the range of 7-10 mU/l. These data support the TSH threshold of 10 mU/l recommended in guidelines, particularly in elderly patients over the age of 65years, in whom TSH serum levels increase with age. In contrast to the recommendations, the prescription of thyroxine more than doubled in alarge study from Denmark and TSH levels decreased from 10 mU/l to under 7 mU/l between 2001 and 2015. As (the primarily unspecific) symptoms and quality of life are not altered by thyroxine replacement in studies on subclinical hypothyroidism and elderly patients are more susceptible to side effects, thyroid hormone substitution should generally not be started at TSH levels <10 mU/l.

The impact of demographic factors on newborn TSH levels and congenital hypothyroidism screening.

Optimal newborn screening thyroid-stimulating hormone (TSH) cut-offs are contentious. Analysis of demographic factors that impact screen TSH levels may help explain international variance and provide guidance to screening programmes. To determine the influence of demographic factors on newborn screening TSH levels and screening performance parameters. National, retrospective population study using blood spot TSH cards from the New Zealand newborn screening programme in 2010-2015. 325685 blood spot cards. Likelihood of exceeding specific TSH thresholds (TSH ≥5, ≥10 and ≥15mIU/L) and group-specific screening performance parameters. The likelihood of high TSH levels differed between ethnic groups. Pacific Island infants were more than twice as likely to have high-normal TSH levels (≥5 and ≥10mIU/L) and nearly twice as likely to have a positive screen (≥15mIU/L) as New Zealand Europeans. Māori or Chinese ethnicity, male sex, younger gestational age and greater socio-economic deprivation scores were also associated with high-normal TSH levels. At a TSH threshold ≥15mIU/L, screening sensitivity was lowest (88.89% vs 95.83% overall) and PPV greatest (88.89% vs 62.84%) amongst Asian infants. Early samples were more than three times as likely to reach the screen-positive threshold and more likely to yield a false-positive result (PPV 20.00% vs 68.87%, P=0.004). Newborn TSH levels are impacted by a number of demographic variables, particularly ethnicity and age at sample collection. Screening performance may be improved through the use of targeted thresholds.

Thyroid Function Changes in the Elderly and Their Relationship to Cardiovascular Health: A Mini-Review

Background: Thyroid hormones have significant effects on the cardiovascular systems. In general, hyperthyroidism is associated with an increased risk of dysrhythmias, while hypothyroidism may cause atherosclerosis. Recent large studies have sought to identify aging-associated changes in thyroid function and their relevance to cardiovascular morbidity and mortality in the elderly. Conflicting results have often been published, likely due to the heterogeneity of the studied populations. Objective: This review seeks to briefly summarize the most recent large population studies analyzing thyroid changes with aging and interpreting their effects on cardiovascular health in the elderly. Methods: Selective review of recent literature. Results: The emerging pattern suggests a slight decrease in thyroid function in the elderly leading to slightly higher thyroid stimulating hormone (TSH) levels. However, the incidence of mild hyperthyroidism also increases, especially in populations with historical or current iodine deficiency. Large observational studies suggest that the potential harm from mild hypothyroidism seen in younger population tends to diminish in older subjects, while the harm from mild hyperthyroidism becomes more significant. A markedly increased risk of atrial fibrillation is a well-established consequence of subclinical hyperthyroidism in patients in the sixth decade of life and beyond. Conclusions: The absence of large prospective interventional data does not allow the formulation of strict clinical recommendations, but a higher TSH threshold for treating both subclinical hypothyroidism and subclinical hyperthyroidism in the elderly seems reasonable.

The impact of thyroid-stimulating hormone levels in euthyroid women on intrauterine insemination outcome

BackgroundThe aim of this study was to examine the effect of thyroid-stimulating hormone (TSH) levels on intrauterine insemination (IUI) outcomes among euthyroid women.MethodsA retrospective cohort study was conducted. A total of 302 women who started their first IUI cycle in our fertility center were included in this study. The patients were categorized into two groups based on their preconception TSH values: 0.38–2.49 mIU/Land 2.50–4.99 mIU/L. The clinical pregnancy rate was the main outcome parameter. As secondary parameters, we evaluated the differences in spontaneous abortion rate, live-birth delivery rate, and perinatal outcomes according to the preconception TSH threshold (< 2.5 and < 5.00 mIU/L).ResultsThere was no significant difference between the two groups with respect to clinical pregnancy, miscarriage, and live-birth rates with an odds ratio of 1.67 (95% CI: 0.79–3.53), 1.08 (95% CI: 0.09–13.1), and 1.79 (95% CI: 0.77–4.2), respectively. In addition, there were no significant differences in perinatal outcomes (gestation at delivery, birth weight, and neonatal intensive care unit–administration rate) between the two groups.ConclusionsOur findings indicate that among euthyroid patients, preconception TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) do not have a negative effect on IUI outcomes.Trial registrationThis study is retrospectively registered by Ethical Review Board at Inonu University in 19th December 2017; Ethics approval no is 2017–27-20.

Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update.

Subclinical thyroid dysfunction comprises subclinical hypothyroidism (SHypo), defined as elevated thyroid-stimulating hormone (TSH) by normal free thyroxine (FT4), and subclinical hyperthyroidism (SHyper) with decreased or undetectable TSH and normal FT4. Up to 10% of the elderly have SHypo, which is usually asymptomatic. Individual participant data (IPD) analyses of prospective cohort studies from the international Thyroid Studies Collaboration show that SHypo is associated with increased coronary heart disease (CHD) mortality [hazard ratio (HR) 1,58 for TSH ≥ 10 mIU/L, 95% CI 1.10-2.27), as well as increased risk of stroke, and heart failure (HF) for both higher and lower TSH. Small studies found that SHypo affects carotid intima media thickness (CIMT), diastolic function, peripheral vascular resistance, endothelial function, and lipid profile. SHyper is associated with increased risk of atrial fibrillation (AF) (HR 1.68, 95% CI 1.16-2.43) and CHD events (HR 1.21, 95% CI 0.99-1.46). The TSH threshold for initiating treatment is unclear. In the absence of large randomized controlled trials, the best evidence suggests SHypo therapy should be started at TSH ≥ 10 mIU/L, and SHyper therapy at TSH < 0.1 mIU/L. Recommendations on screening are discordant, but most guidelines advocate that thyroid function should be checked in those at risk for hypothyroidism, those over 60, and those with known CHD and HF. This review updates current evidence on the association between thyroid dysfunction and cardiovascular disease, as well as on screening and treatment of subclinical thyroid dysfunction.

Impact of thyroid autoimmunity in euthyroid women on live birth rate after IUI.

Does thyroid autoimmunity (TAI) predict live birth rate in euthyroid women after one treatment cycle in IUI patients? TAI as such does not influence pregnancy outcome after IUI treatment. The role of TAI on pregnancy outcome in the case of IVF/ICSI is largely debated in the literature. This is the first study to address this issue in the case of IUI. This was a retrospective cohort study. A two-armed study design was performed: patients anti-thyroid peroxidase (TPO)+ and patients anti-TPO-. All patients who started their first IUI cycle in our fertility center between 1 January 2010 and 31 December 2014 were included. After exclusion of those patients with or being treated for thyroid dysfunction, 3143 patients were finally included in the study. After approval by the institutional review board we retrospectively included all patients who started their first IUI cycle in our center between 1 January 2010 and 31 December 2014 with follow-up of outcome until 31 December 2015. Patients with clinical thyroid dysfunction were excluded (thyroid-stimulating hormone (TSH) <0.01 mIU/l; TSH >5 mIU/l) as were patients under treatment with levothyroxine or anti-thyroid drugs. These patients were then divided into two main groups: patients anti-TPO+ and patients anti-TPO- (= control group). Live birth delivery after 25 weeks of gestation was taken as the primary endpoint of our study. As a secondary endpoint, we evaluated differences in live birth delivery after IUI according to different upper limits of preconception TSH thresholds (<2.5 and <5.0 mIU/l). Furthermore, the influence of thyroid function (TSH, free thyroxine (fT4)), anti-TPO status, age, smoking, BMI, parity, ovarian reserve (anti-mullerian hormone (AMH) and FSH), IUI indication and IUI stimulation on live birth rate was analyzed. Between-group comparison did not show any significant difference between the anti-TPO+ and anti-TPO- group with respect to live birth delivery-, pregnancy- or miscarriage rate with odds ratio at 1.04 (95% CI: 0.63; 1.69), 0.98 (95% CI: 0.62; 1.55) and 0.74 (95% CI: 0.23; 2.39), respectively. In addition, there were no significant differences in live birth delivery-, pregnancy- or miscarriage rate when comparing subgroups according to TSH level (TSH ≥2.5 mIU/l vs. TSH <2.5 mIU/l) with an odds ratio at 1.05 (95% CI: 0.76; 1.47), 1.04 (95% CI: 0.77; 1.41) and 0.95 (95% CI: 0.47; 1.94), respectively. This study was powered for the primary aim, live birth rate. The limitations of this study are the absence of region-specific reference ranges for thyroid hormones and the absence of follow-up of TSH values during ART and subsequent pregnancy. Moreover, there was a time difference of 5 months between thyroid assessment and the start of stimulation. The area where the study was conducted corresponds to a mild iodine deficient area and data should be translated with caution to areas with different iodine backgrounds. Our findings indicate comparable pregnancy-, abortion- and delivery rates in women with and without TAI undergoing IUI. Moreover, we were unable to confirm a negative effect of TSH level above 2.5 mIU/l on live birth delivery rate. We therefore believe that advocating Levothyroxine treatment at TSH levels between 2.5 and 4 mIU/l needs to be considered with caution and requires further analysis in a prospective cohort study. No external funding was used for this study. No conflicts of interest are declared.

How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

ObjectivesTo determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of <10 pmol/L is unlikely, so...

Thyroid screening in pregnancy

The adverse impact of overt hypothyroidism that complicates pregnancy outcomes is well-established and not debated. For more than a decade, however, endocrinologists and obstetricians have been debating whether screening for subclinical thyroid disorders during pregnancy should be routine or should continue to be based on symptoms and risk factors. Several observational studies have suggested that offspring of women with asymptomatic thyroid dysfunction were at increased risk for impaired neurodevelopment. Other studies have suggested that pregnant women with subclinical thyroid disease, particularly those identified with an elevated thyroid-stimulating hormone (TSH) level may be at increased risk for pregnancy complications such as fetal death, preterm birth, or placental abruption. These data have prompted both obstetric and endocrinologic professional societies to draft recommendations regarding screening for thyroid disease during pregnancy, some of which are not entirely based on available evidence. The prevalence of overt thyroid disease is estimated to be 1-2 per 1000 pregnancies and historically has not been considered high enough to justify routine screening. Lower TSH thresholds (>2.5 mU/L) for the diagnosis of hypothyroidism have been promoted, and women with subclinical thyroid dysfunction commonly are included in estimates of thyroid disease during pregnancy, both of which exaggerate prevalence rates. The most compelling recent evidence on this issue has come from the Controlled Antenatal Thyroid Screening trial. After almost 22,000 pregnant women were screened for either isolated high TSH or isolated low free thyroxine level, 390 children of treated women with either diagnosis were compared with 404 children of similar women who were not treated during pregnancy. Treatment had no effect on mean offspring IQ at age 3 years or the number of children with an IQ <85. Authors of this landmark study concluded that antenatal screening and maternal treatment for women with subclinical thyroid dysfunction did not result in improved cognitive function. An ongoing intervention trial conducted by the Eunice Kennedy-Shriver National Institute of Child Health and Human Development's Maternal-Fetal Medicine Units Network will provide further clarity to this important question. In the interim, the debating authors have concluded, after careful review of the currently published literature, that routine screening for subclinical thyroid dysfunction during pregnancy is not currently warranted at this time.