The GLP-1 receptor agonist exenatide reduces serum TSH by its effect on body weight in people with type 2 diabetes.

OBJECTIVE: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in patients with type 2 diabetes and obesity leads to a significant reduction in serum thyrotropin (TSH) levels but it is unclear whether this is related to weight loss and improvement in sensitivity to thyroid hormones (TH). DESIGN, PATIENTS AND MEASUREMENTS: We prospectively analysed clinical and biochemical data in patients with type 2 diabetes and obesity who were commenced on the GLP-1 RA exenatide and followed them for 12 months. We assessed the relationship between changes in body weight and serum TSH and resistance to TH indices. RESULTS: In 112 patients (mean age: 53.5 years, 43.8% female, mean body mass index: 39.8 kg/m2 ), 12 months of exenatide treatment was associated with a mean (95% CI) percent body weight loss of 6.5% (5.0%-8.1%) and change in serum TSH of -0.25 mU/L (-0.43 to -0.06). There was a significant negative and nonlinear relationship between change in serum TSH and percent body weight loss: -0.25 mU/L with 5%, -0.4 mU/L with 10% and -0.5 mU/L with 15%, respectively, whereas a rise in serum TSH of 0.5 mU/L was associated with 5% weight gain. There were no changes observed in serum FT4 levels with weight loss but a significant reduction in resistance to TH indices was noted. CONCLUSIONS: Exenatide therapy reduces serum TSH levels and improves central sensitivity to TH action over 12 months via its effect on weight loss. The effectiveness of weight loss strategies, rather than TH replacement, should be investigated in individuals with obesity and mildly raised serum TSH levels.

Possible Contributions of Nongenomic Actions of Thyroid Hormones to the Vasculopathic Complex of COVID-19 Infection.

BACKGROUND: Integrin αvß3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)-when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction-may enhance cellular uptke of SARS-CoV-2 and its receptor. OBJECTIVE: Because T4 also acts nongenomically via the integrin to promote platelet aggregation and angiogenesis, we suggest here that T4 may contribute to the coagulopathy and endothelial abnormalities that can develop in COVID-19 infections, particularly when the lung is primary affected. DISCUSSION AND CONCLUSIONS: Elevated FT4 has been described in the NTIS of COVID-19 patients and may be associated with increased illness severity, but the finding of FT4 elevation is inconsistent in the NTIS literature. Circulating 3,5',3'-triiodo-L-thyronine (reverse T3, rT3) are frequently elevated in NTIS. Thought to be biologically inactive, rT3in fact stimulates cancer cell proliferation via avb3 and also may increase actin polymerization. We propose here that rT3 in the NTIS complicating systemic COVIF-19 infection may support coagulation and disordered blood vessel formation via actin polymerization.

Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays.

INTRODUCTION: Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated. METHODS: After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed. RESULTS: FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer's reference interval. CONCLUSIONS: Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.

The diagnosis and management of subclinical hypothyroidism is assay-dependent- Implications for clinical practice.

OBJECTIVE: We assessed the commutativity of Roche and Abbott thyroid assays in the diagnosis and management of subclinical hypothyroidism (SCH). The Roche and Abbott thyroid assays are used by approximately 75% of clinical laboratories in the UK. METHOD: Consecutive samples received from primary care on patients with SCH who had a raised thyroid-stimulating hormone (TSH) <10 mIU/L and a normal free thyroxine (fT4) from two laboratories using either Roche or Abbott thyroid assays were identified over 10 working days. Following identification, samples were analysed at the other site within 24 hours. Diagnostic and management discordance were studied using the relevant manufacturer-provided reference ranges. RESULTS: We identified 93 patients with SCH (53 using the Roche assay). Roche TSH and fT4 results were respectively 40% ± 15% and 16% ± 7% higher (P < .001) compared to Abbott results. Of the 93 patients, 41 (44%) were concordant for SCH on both methods. Of the 53 patients with SCH on the Roche assays, 40 (75.5%) had normal thyroid function and 13 (24.5%) had SCH when analysed using the Abbott assays. Of the 40 patients with SCH on the Abbott assays, 28 (70%) had SCH and 12 (30%) had results indicative for levothyroxine replacement when analysed on the Roche assays. Of these 12 patients, four had TSH > 10 mIU/L, five had low fT4 and three had both. CONCLUSION: The diagnosis and management of SCH is strikingly different when using TSH and fT4 assays provided by Abbott Laboratories and Roche Diagnostics. Clinicians and laboratorians should be aware that between-assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism.

Biological variation and analytical goals of four thyroid function biomarkers in healthy European volunteers.

BACKGROUND: Interpretation of thyroid function tests by means of biological variation (BV) data is essential to identify significant changes between serial measurements at an individual level. Data on thyroid parameters in adults are limited. OBJECTIVES: We aimed at determining the BV of four thyroid function test (thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3) and thyroglobulin (Tg)) by applying recent recommendations to acquire BV data on a latest generation of immunoassay. METHODS: Nineteen healthy volunteers (8 males and 11 females) were drawn every week during 5 consecutive weeks. Samples were analysed in duplicate on the Cobas 602 analyzer (Roche Diagnostics). After normality assessment, outlier exclusion and homogeneity of variance analysis, analytical variation (CVA ), within-subject biological variation (CVI ) and between-subject biological variation (CVG ) were determined using nested ANOVA. RESULTS: CVA , CVI and CVG were 0.9%, 19.7% and 37.6% for TSH; 3.6%, 4.6% and 10.8% for FT4; 2.2%, 6.0% and 8.6% for FT3; and 0.9%, 15.4% and 84.9% for Tg. Index of individuality (II) for all parameters was between 0.2 and 0.7. The percentage above which the change between two measures is truly significant (reference change value) was 54.7% for TSH, 16.2% for FT4, 17.7% for FT3 and 42.8% for Tg. CONCLUSION: Based on recent international recommendations, our study provides updated BV data for four thyroid function tests in European healthy volunteers. Reliable BV characteristics, and especially RCV, can facilitate the interpretation of consecutive thyroid function tests in an individual and therefore have the potential to efficiently support clinical decisions regarding thyroid diseases.

USE OF THE FREE THYROXINE INDEX TO REFINE THE LOWER LIMIT OF A FREE THYROXINE IMMUNOASSAY FOR DETECTION OF SECONDARY HYPOTHYROIDISM.

OBJECTIVE: To determine the utility of measuring free T4 index (FT4I) in patients with low free T4 (FT4) levels using immunoassay and normal thyroid-stimulating hormone for the evaluation of secondary hypothyroidism. METHODS: We performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal thyroid-stimulating hormone level, low FT4 level, and any FT4I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT4I as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of the FT4 immunoassay's lower-limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation were categorized according to the presence or absence of pituitary disease. RESULTS: A total of 155 sets of result pairs (FT4 and FT4I) performed on 118 subjects were analyzed. The lower limit of a normal FT4 level by immunoassay at this institution was 0.93 ng/dL, though all pairs with FT4 ≥0.89 ng/dL had a normal FT4I. All pairs with FT4 ≤0.67 ng/dL had a low FT4I. No pituitary macroadenomas were identified in any subject, though the rates of pituitary imaging in this patient sample were low. CONCLUSION: Patients with a borderline low FT4 level by immunoassay often have normal FT4I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon.

Impact of an Interprofessional Collaborative Quality Improvement Initiative to Decrease Inappropriate Thyroid Function Testing.

Background: Published data show that thyroid function laboratory tests are often ordered inappropriately in the acute care setting, which leads to unnecessary costs and inappropriate therapy decisions. Pilot data at our institution indicated that approximately two-thirds of the thyroid-stimulating hormone (TSH) laboratories were unnecessary, correlating to a potential cost avoidance of more than $20,000 annually. The purpose of this study was to improve the appropriateness of thyroid function test ordering with a multipronged initiative. Methodology: This controlled, single-center, before and after study included inpatients or emergency department (ED) patients at Wake Forest Baptist Medical Center who were at least 18 years of age and had a TSH level ordered during the study period. Patients with a history of thyroid cancer were excluded. The initiative included an electronic ordering intervention, direct education of providers (medical residents, attendings, and clinical pharmacists), and distribution of pocket information cards with appropriate ordering criteria. The primary outcome was the number and percentage of inappropriate TSH tests ordered before and after implementing the 3 interventions. Secondary outcomes included cost savings, inappropriate changes in thyroid therapy based on improperly ordered tests, and the number of free T4 lab tests ordered on patients with a TSH within the therapeutic range. Results: All 3 interventions were implemented, except for education of ED residents and faculty, who chose to forgo the direct education component. Inappropriate ordering of TSH levels decreased from 63 to 50 (13% reduction, P = .062) after implementation. Inappropriate TSH ordering decreased across all services, except in the ED. Inappropriate Free T4 orders decreased from 191 to 133 (30% reduction, P = .01). There were no therapy changes based on inappropriate TSH orders. Extrapolated annual cost savings were approximately $6,000. Conclusion: This multipronged interprofessional collaborative quality improvement initiative was associated with a nonstatistically significant reduction in inappropriate TSH orders, statistically significant reduction in inappropriate free T4 orders, and cost savings. There was a reduction in inappropriate ordering across all services except the ED, which may have been due the ED not participating in the direct education component of the initiative.

Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down síndrome.

INTRODUCTION: Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored. OBJECTIVE: To determine whether FHTD is associated with an increased incidence of CH in neonates with DS. METHOD: Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. RESULTS: Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). CONCLUSIONS: Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

INTRODUCCIÓN: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. OBJETIVO: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. MÉTODO: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). RESULTADOS: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). CONCLUSIONES: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

A 2019 update on TSH-secreting pituitary adenomas.

Thyrotropin-secreting pituitary adenomas (TSH-omas) present with signs and symptoms of hyperthyroidism and they are characterized by elevated serum levels of free thyroid hormones with measurable TSH levels. TSH-omas are very infrequent, accounting for less than 1% of all pituitary adenomas, thus representing a very rare cause of hyperthyroidism. For this reason, data collected on these rare disorders are relatively few, but some new researches shed new light on the etiopathogenesis, the diagnosis and the treatment of such a remarkable disease. Since the same biochemical picture is present in the syndromes of thyroid hormone resistance (RTH), in particular in the form of pituitary RTH, failure in distinguishing these clinical entities may lead to improper patient management. Conversely, early diagnosis and correct treatment of TSH-omas may prevent the occurrence of neurological and endocrinological complications, thus leading to a better rate of cure. In the present short review article, the most relevant recent advances in the pathophysiology of TSH-omas are described.

Evaluation of thyroid test utilization through analysis of population-level data.

BACKGROUND: Inappropriate laboratory test utilization can result in unnecessary patient testing and increased healthcare costs. While several thyroid function tests are available, thyroid-stimulating hormone (TSH) is recommended as the first-line test for investigating and monitoring thyroid dysfunction. We evaluate thyroid test utilization in Northern Alberta in terms of testing patterns, frequencies, and reflex cutpoints. METHODS: This retrospective study analyzed thyroid test requests from January to December 2014. Each request was designated as appropriate or potentially inappropriate as per clinical practice guidelines and Choosing Wisely recommendations, and the frequencies of each testing pattern were calculated. Sub-analysis was performed to categorize testing patterns based on physician specialty. The number of test requests per patient was determined to assess the appropriateness of testing frequency. Receiver operating characteristic (ROC) curves were generated to define optimal TSH cutpoints for automatic reflex to FT4 testing. RESULTS: Of 752,217 test requests, approximately 10% were potentially inappropriate in terms of testing patterns. Free thyroxine (FT4) and free triiodothyronine (FT3) requested with TSH accounted for 59% of all potentially inappropriate test requests, and 49% of requests from endocrinologists (ENDO) were potentially inappropriate, occurring most frequently among those with less experience. Excessive testing frequencies were observed in 869 patients, accounting for 9382 test requests. Adjustment of our TSH reflex cutpoint would significantly increase specificity for identifying a low FT4 without compromising sensitivity. CONCLUSIONS: This study suggests that questionable testing patterns, excessive testing frequencies, and suboptimal reflexive testing cutpoints contribute to inappropriate thyroid test utilization.

The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case-control study.

PURPOSE: To study the effects of gestational transient thyrotoxicosis (GTT) on pregnancy outcomes. METHODS: This case-control study retrospectively analyzed 7976 women with singleton pregnancies whose thyroid function was measured before 16 weeks of gestation and who delivered at ≥22 weeks of pregnancy. GTT was defined as hyperthyroidism (free thyroxine [FT4] level: ≥95th percentile) in the early pregnancy, which normalized in mid-pregnancy without thyroid-stimulating hormone receptor antibodies. Using data extracted from electronic records, we examined the association between GTT and the pregnancy outcomes (preterm delivery, gestational age at delivery, pregnancy induced hypertension (PIH), preeclampsia, placental abruption, caesarian section, birth weight, low birth weight, Apgar score, cord pH, stillbirth at gestational week ≥22, and neonatal death). We classified the cases into quartiles according to their FT4 values during the early pregnancy and investigated the association with the gestational age at delivery. RESULTS: Two hundred and eight cases of GTT and 6317 cases with normal thyroid assessments were reviewed. GTT was associated with hyperemesis gravidarum, but not with stillbirth, preterm delivery, PIH, preeclampsia, placental abruption, or low birth weight. The gestation period was shorter in patients with GTT than in those with a normal thyroid function (38.69 ± 1.79 vs. 39.07 ± 1.64 weeks, p < 0.01). Higher FT4 levels during the early pregnancy were associated with earlier delivery (p = 0.02). CONCLUSIONS: GTT was associated with a lower gestational age at delivery but not with adverse pregnancy outcomes. There was a negative correlation between the FT4 values in the early pregnancy and the gestational period.

Amniotic fluid paraoxonase-1 activity, thyroid hormone concentration and oxidant status in neural tube defects.

AIM: The aim of this study was to investigate the potential association between neural tube defects and paraoxonase-1 activity in amniotic fluid. We studied total oxidant status, total antioxidant capacity, paraoxonase-1 activity and thyroid hormone amniotic fluid concentration in fetuses with neural tube defects. METHODS: The present study was performed at the Department of Obstetrics and Gynaecology and the Department of Clinical Biochemistry of Dicle University between September 2011 and June 2013. The study group included 37 amniotic fluid samples from pregnant women (16-20 weeks of gestation) with fetuses affected by neural tube defects. The control group consisted of 36 pregnant women who were diagnosed with a high-risk pregnancy according to first or second trimester aneuploidy screening and were later confirmed on amniocentesis to have genetically normal fetuses. RESULTS: Amniotic fluid paraoxonase-1 activity and total oxidant status were significantly higher (P = 0.023, P = 0.029, respectively) whereas free T4 was significantly lower (P = 0.022) in fetuses with neural tube defects compared with control subjects. In fetuses with neural tube defects, amniotic fluid paraoxonase-1 activity correlated positively with total oxidant status (r = 0.424**, P = 0.010), and amniotic fluid total antioxidant capacity correlated positively with free t4 (r = 0.381*, P = 0.022). CONCLUSION: This is the first study in the literature to show an association between paraoxonase-1 activity and thyroid hormone concentration and neural tube defects.

Clinical analysis of 65 cases of hyperemesis gravidarum with gestational transient thyrotoxicosis.

AIM: We investigated thyroid function and the impact of gestational transient thyrotoxicosis (GTT) on pregnancy outcome in patients with hyperemesis gravidarum (HG; n = 143) who were hospitalized for rehydration. METHODS: Serum thyroid-stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), thyroid globulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and hCG were measured after admission. RESULTS: The total prevalence of thyrotoxicosis in HG was 48.3%; GTT was the main form (45.5%). The total incidence of GTT increased significantly if serum hCG was more than 80,000 IU/L, subclinical GTT if serum hCG was 80,000-140,000 IU/L and clinical GTT if serum hCG was more than 180,000 IU/L. GTT did not require antithyroid therapy. The course of TSH, FT3 and FT4 were followed in 34 cases of GTT; thyroid function normalized by the second trimester. Of 65 patients with GTT, two underwent abortions due to unplanned pregnancies, two delivered prematurely and two infants had macrosomia. There were no other complications. All newborns (n = 63) of mothers with GTT had normal TSH levels. CONCLUSION: GTT is common in HG. The severity of GTT is related to serum hCG levels. In patients with HG and GTT, thyroid function normalized by the second trimester without antithyroid treatment. GTT did not affect pregnancy outcomes.

Hypothyroidism and Its Impact on Menstrual Irregularities in Reproductive-Age Women: A Comprehensive Analysis at a Tertiary Care Center.

BACKGROUND: Hypothyroidism is known to affect a wide range of physiological systems, including menstrual function, in women of reproductive age. This study aims to comprehensively analyze the association between hypothyroidism and menstrual irregularities in women attending a tertiary care center. METHODS: The study included 120 women aged 18-45 who presented with menstrual abnormalities. Convenience sampling was used to select participants from the outpatient department of obstetrics and gynecology. Thyroid function tests were conducted in the hospital's biochemistry laboratory, including assessments of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid peroxidase antibodies (TPOAb). The study aimed to determine the prevalence of hypothyroidism and its association with various menstrual irregularities, such as oligomenorrhea, polymenorrhea, menorrhagia, and amenorrhea. Data analysis was performed using SPSS software, applying descriptive statistics, Pearson correlation for continuous variables, and Chi-square tests for categorical variables. A significance level of p<0.05 was set for the analyses. RESULTS: The mean age of the participants was 33.1 years (SD ± 7.2). The distribution of menstrual irregularities was 60 (50%) oligomenorrhea, 24 (20%) polymenorrhea, 24 (20%) menorrhagia, and 12 (10%) amenorrhea. Elevated TSH levels (>4.0 mIU/L) were observed in 42 (35%) of the participants, low FT4 levels (<0.8 ng/dL) in 18 (15%), low FT3 levels (<2.5 pg/mL) in 12 (10%), and elevated TPOAb levels (>55 IU/mL) in 24 (20%). A significant association was found between elevated TSH levels and oligomenorrhea (66 (55%), p<0.05) and between reduced FT4 levels and menorrhagia (78 (65%), p<0.05). Additionally, elevated TPOAb levels were significantly associated with amenorrhea (60 (50%), p<0.05). The correlation analysis showed a moderately positive correlation between TSH levels and the severity of menstrual irregularities (r=0.35, p<0.01). Subclinical hypothyroidism was detected in 25% of the participants, while 15% had clinical hypothyroidism. CONCLUSION: This study underscores a notable link between hypothyroidism and menstrual irregularities in women of reproductive age. The results highlight the necessity of routine thyroid function screenings for women experiencing menstrual abnormalities, facilitating precise diagnosis and suitable treatment.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification.

This study investigated the potential associations between hepatitis virus antibody status and thyroid and inflammatory function. The C-reactive protein (CRP), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were measured in individuals with and without antibodies to the hepatitis A virus (HAV) and hepatitis B virus (HBV). Participants were stratified by age, sex, and HAV/HBV antibody status. Participants with and without antibodies to HAV and HBV had normal CRP, TSH, and FT4 levels. However, notable discrepancies were observed in FT4 levels among participants with HAV antibodies and in CRP and FT4 levels among those with both HAV and HBV antibodies, suggesting potential associations between viral immunity and thyroid function, especially in younger participants. Significant variations in thyroid hormone levels were noted when the sample was stratified by sex and HAV and HBV antibody status, indicating that the association between antibody status and thyroid hormone levels varied by sex. This study underscores the need for further research on the effect of viral immunity on inflammatory parameters and thyroid hormone levels.

Insights into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.

CONTEXT: Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. OBJECTIVES: To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. DESIGN: Multicenter cross-sectional retrospective chart review. SETTING: Nine pediatric endocrine units throughout Israel. PATIENTS: Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. RESULTS: CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. CONCLUSIONS: Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.

Exposure to monocrotophos pesticide causes disruption of the hypothalamic-pituitary-thyroid axis in adult male goldfish (Carassius auratus).

The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic-pituitary-thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone ß subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.