Explore the vast range of titles available.

Abstract Background Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per .1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were −5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity, .70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were −20% for the upper limit of TSH and −15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

The IFCC Committee for Standardization of Thyroid Function Tests intended to standardize free thyroxine (FT ) immunoassays. We developed a Système International d'Unités traceable conventional reference measurement procedure (RMP) based on equilibrium dialysis and mass spectrometry. We describe here the latest studies intended to recalibrate against the RMP and supply a proof of concept, which should allow continued standardization efforts. We used the RMP to target the standardization and reference interval (RI) panels, which were also measured by 13 manufacturers. We validated the suitability of the recalibrated results to meet specifications for bias (3.3%) and total error (8.0%) determined from biological variation. However, because these specifications were stringent, we expanded them to 10% and 13%, respectively. The results for the RI panel were reported as if the assays were recalibrated. We estimated all but 1 RI using parametric statistical procedures and hypothesized that the RI determined by the RMP was suitable for use by the recalibrated assays. Twelve of 13 recalibrated assays had a bias, meeting the 10% specification with 95% confidence; for 7 assays, this applied even for the 3.3% specification. Only 1 assay met the 13% total error specification. Recalibration reduced the CV of the assay means for the standardization panel from 13% to 5%. The proof-of-concept study confirmed our hypothesis regarding the RI but within constraints. Recalibration to the RMP significantly reduced the FT immunoassays' bias, so that the RI determined by the RMP was suitable for common use within a margin of 12.5%.

Background and Objectives: Given that hormone levels vary with age, the application of age-specific reference intervals in older populations is clinically essential. In this study, we aimed to establish age- and sex-specific reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy individuals aged ≥65 in Eastern Turkey using an indirect statistical method. Materials and Methods: This retrospective study included 3835 individuals (1986 males and 1849 females) who were evaluated at Elazığ Fethi Sekin City Hospital between 2020 and 2025. According to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guidelines, reference intervals were determined using a laboratory database–based indirect reference interval estimation approach with nonparametric percentile methods following a posteriori reference population selection, and the Harris–Boyd criteria were applied for age and sex partitioning. Results: The established reference intervals for those aged ≥65 years were 2.40–4.03 pg/mL for fT3, 0.60–1.27 ng/dL for fT4, and 0.41–3.94 mIU/L for TSH. While fT3 levels declined with age, TSH and fT4 levels did not differ consistently across age subgroups. Sex-based differences were significant: fT3 levels were higher in males, whereas fT4 and TSH levels were higher in females. According to the Harris–Boyd analysis, separate reference intervals are recommended for males and females. Conclusions: For healthy older individuals living in Eastern Türkiye, sex-specific reference intervals should be used for thyroid function tests, whereas age-specific reference intervals are sufficient for fT3.

Background Thyroid disorders are common in the adult German population. Little is known about guideline implementation in clinical practice and the prevalence of diagnostic procedures in ambulatory care. The study aims to investigate the use of thyroid hormone measurements, thyroid ultrasound, thyroid scintiscan and associated costs in ambulatory care at population level. Methods Data were derived from two independent population-based cohorts of the Study of Health In Pomerania (SHIP). Ambulatory billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were individually linked for the period 2002–2016 with SHIP data. The main outcomes were the frequency of outpatient ultrasound, scintiscan, serum TSH level measurement, free triiodothyronine (fT3) and free thyroxine (fT4) measurement, TSH-receptor-antibodies and microsomal antibodies measurement within 1 year and 3 years prior to the study entrance of the participants. Multinomial logistic regression models were used to assess the association of age, sex, thyroid medication intake and Charlson-Comorbidity-Index with frequency of TSH measurements and ultrasound examinations. Results A total of 5552 participants (47% male, median age 55) were included in the analysis. 25% (1409/5552) had a diagnosed thyroid disorder or treatment, 40% (2191/5552) had clinical findings based on ultrasound or laboratory testing in SHIP only and 35% (1952/5552) neither a coded thyroid disorder or clinical finding nor thyroid medication. In the total study population 30% (1626/5552) received at least one TSH measurement, 6.8% (378/5552) at least one thyroid ultrasound and 2.6% (146/5552) at least one scintiscan within the past year before the study examination. Tests were performed more frequently in patients with thyroid medication and coded thyroid disorders. Hence, this group caused the highest expenditures. Conclusions Given the high prevalence of thyroid disorders, diagnostic and monitoring tests should be used rationally with regard to costs. TSH levels should be monitored regularly in patients on thyroid medication. A consensus on monitoring frequency and iteration of monitoring of morphological thyroid disorders with TSH and ultrasound and specific guideline recommendations are needed. Trial registration Versorgungsforschung Deutschland (VfD_17_003880).

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.

Laboratory stewardship programs are increasingly adopted to enhance test utilization and improve patient care. Despite their potential, implementation within complex healthcare systems remains challenging. Benchmarking metrics helps institutions compare their performance against peers or best practices. However, the application in laboratory stewardship is underrepresented in the literature. The PLUGS (Patient-centered Laboratory Utiliazation Guidance Services) Informatics Working Group developed guidelines to address common test utilization issues. Metrics were based on data that are easily retrievable and calculable. Three key benchmarks were chosen for a pilot study: the ratio of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D test orders, the ratio of thyroid-stimulating hormone (TSH) to free thyroxine (FT4) test orders, and the percentage of iron workup orders after an initial low mean corpuscular volume (MCV). Institutions analyzed their own data and we established optimal benchmarks through inter-laboratory comparisons. Nine laboratories evaluated vitamin D testing, with 2 implementing stewardship interventions beforehand. A benchmark of 50:1 was established, where a higher ratio indicates intentional ordering of 1,25-dihydroxyvitamin D. Nine laboratories evaluated thyroid testing, with 3 implementing interventions. The benchmark of 3.5:1 was established, with a higher ratio suggesting judicious TSH ordering. Seven laboratories evaluated iron workups, proposing a benchmark of 50% as a starting metric. Intervention guidelines were provided for laboratories below the benchmarks to promote improvement. Benchmarking metrics provide a standardized framework for assessing and enhancing test utilization practices across multiple laboratories. Continued collaboration and refinement of benchmarking methodologies is essential in maximizing the impact of laboratory stewardship programs on patient safety and resource utilization.

Disorders of the thyroid gland are relatively frequent in women of childbearing age and can result in poor pregnancy outcome. The authors of this Perspective are in favor of serum TSH measurement for all pregnant women and present relevant information on analytical and clinical aspects of serum TSH determination and its usefulness to detect subtle thyroid function abnormalities associated with the pregnant state, namely overt and subclinical hypothyroidism and hyperthyroidism. Improvements in the sensitivity of the serum TSH assay have revolutionized our strategies for investigating thyroid function and firmly established TSH as the first-line thyroid function test for most clinical situations, including pregnancy. As a single hormone determination, serum TSH provides the most sensitive index to reliably detect thyroid function abnormalities. Normal thyroid function is important to ensure the best possible pregnancy outcome; in addition, disorders of the thyroid gland are relatively frequent in women of childbearing age. The aim of this article is, therefore, to present relevant information on analytical, as well as clinical, aspects regarding serum TSH determination and its usefulness to detect subtle thyroid function abnormalities associated with the pregnant state, namely overt and subclinical hypothyroidism and hyperthyroidism. As these disorders are associated with poor pregnancy outcome, the authors of the present article are in favor of serum TSH measurement for all pregnant women.

Abstract Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves’ disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves’ disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment.

To investigate a dose dependency of thyroperoxidase antibody (TPOAb) concentrations in relation to thyroid function and premature delivery and define a population-based, pregnancy-specific, functional cutoff for TPOAb positivity. Individual participant meta-analysis of three prospective birth cohorts: the Amsterdam Born Children and their Development study, and the Holistic Approach to Pregnancy. Population-based studies in the Netherlands (2002 to 2014). A total of 11,212 pregnant women (<20 weeks' gestation). Thyrotropin (TSH) and FT4 concentrations, premature delivery. In all cohorts, there was a dose-dependent positive association of TPOAb concentrations with TSH concentrations, as well as a dose-dependent negative association with FT4 concentrations during early pregnancy (all P < 0.0001). There was a dose-dependent association of TPOAb concentrations with the risk of premature delivery, which was also modified by TSH concentrations. Women with TPOAb concentrations from the 92nd percentile upward had a higher TSH and a higher risk of a TSH >2.5 mU/L (range, 19.4% to 51.3%). Stratified analyses showed that women with TPOAb concentrations below manufacturer cutoffs already had a higher risk of premature delivery, especially when TSH concentrations were high or in the high-normal range. This study demonstrated a dose-dependent relationship between TPOAbs and thyroid function as well as the risk of premature delivery. Furthermore, our results indicate that the currently used cutoffs for TPOAb positivity may be too high. Furthermore, the use of a population-based cutoff for TPOAbs may identify women with a clinically relevant extent of thyroid autoimmunity and a higher risk of premature delivery but that would not be considered TPOAb positive or eligible for treatment otherwise.

Abstract Background Nonthyroidal illness syndrome (NTIS) can result in thyroid function test alterations that mimic hypothyroidism. The duration of NTIS-induced changes in dogs is not well-described. Objectives Document alterations in thyroid function tests during NTIS and recovery, and the time necessary for their resolution. Animals From 103 dogs sampled, 25 euthyroid dogs with acute, resolvable illness having a low serum total thyroxine (TT4) concentration on admission were analyzed. Methods Prospective observational study. Serum TT4 concentration was measured in 103 dogs within 4 hours of admission. If below the reference interval (RI), subsequent serum samples were obtained every 24 hours from admission until discharge (acute phase) and at 2 weeks and 4 weeks after discharge (recovery phase). Serum samples were submitted for batch measurement of serum TT4, free thyroxine (fT4), total 3,5,3′-triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) concentrations. Results In the cohort of dogs analyzed, serum TT4, TT3, and fT4 concentrations were below the RI in 100%, 80%, and 16% at admission; 20%, 80%, and 0% at discharge; 4%, 8%, and 0% at 2 weeks; and 0%, 0%, and 0% at 4 weeks, respectively. Serum TSH concentration was within the RI in 100% at admission and discharge, and above the RI in 4% and 12% at 2 weeks and 4 weeks, respectively. Conclusions and Clinical Importance Naturally occurring NTIS in dogs induces alterations in thyroid function tests during acute illness and recovery. Measurement of serum TT4 concentration 2 to 4 weeks after discharge or serum fT4 concentration by ED during illness is recommended for accurate assessment of thyroid function in acutely ill dogs.