Thyroid-stimulating Hormone Concentrations Research Articles

Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, and dementia risk: results from the NHANES 2011–2012 and Mendelian randomization analysis

IntroductionAs the world ages, dementia places a heavy burden on society and the economy, but current methods of diagnosing dementia are still limited and there are no better therapies that target the causes of dementia. The purpose of this work is to explore the relationship between thyroid disease, thyroid stimulating hormone (TSH) concentrations, free tetraiodothyronine (FT4) concentrations and cognitive function.MethodsThis study utilized cognitive function and thyroid data from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between different groups of TSH and FT4 concentrations and cognitive function using weighted logistic regression and restricted cubic spline (RCS), and then used two-sample Mendelian Randomization (MR) to assess the causal relationship between hyperthyroidism, hypothyroidism, TSH and FT4 concentrations with dementia.ResultsOur analysis of the 2011–2012 NHANES data showed that the individuals with low TSH concentrations had higher Alzheimer’s Disease Word List Registry Consortium1 (CERAD1) and CERAD.delay.recall scores than individuals with high TSH concentrations, and individuals with low FT4 concentrations had higher CERAD3 and Animal Fluency Test scores than individuals with high FT4 concentrations. Our results also showed a non-linear relationship between serum TSH and FT4 concentrations and the Animal Fluency Test. The TSH concentrations within the range of 1.703 to 3.145 mIU/L exhibit a positive correlation with Animal Fluency Test, whereas concentrations outside this range are negatively correlated with Animal Fluency Test. The FT4 concentrations exhibited a positive correlation with Animal Fluency Test to the left of the FT4 concentrations inflection point (0.849 ng/L), whereas to the right of this inflection point, correlation was negative. MR analysis results further indicate that genetic predisposition to hyperthyroidism may be associated with a reduced risk of dementia and vascular dementia(VaD). Conversely, genetic predisposition to hypothyroidism appears to be linked with an increased risk of dementia and VaD. Additionally, genetic predisposition to elevated TSH concentrations may be correlated with a heightened risk of risk of Alzheimer’s disease (AD).ConclusionThis study provides evidence of a nonlinear relationship between TSH and FT4 concentrations and cognitive function, with hyperthyroidism decreasing the risk of dementia and VaD, hypothyroidism increasing the risk of dementia and VaD, and elevated serum TSH concentrations increasing the risk of AD. Furthermore, prioritizing early detection, diagnosis, and treatment through the assessment of thyroid function in individuals at high risk for developing dementia is of paramount importance. This strategy has the potential to significantly contribute to the prevention and deceleration of dementia progression.

Propylthiouracil thyroid manipulation positively affects the metabolic adaptability of primiparous dairy cows to early lactation requirements

The study examined effects of thyroid manipulation with propylthiouracil (PTU) on the metabolic adaptability of transitional dairy cows to early lactation. The study included 30 primiparous Holstein-Friesian cows, which were divided into two groups: PTU+ (n = 15; received orally 4 mg/kg PTU during 20 days before expected calving) and PTU− (n = 15; did not receive orally PTU). Blood was sampled from each cow consecutively from − 20, − 17, − 13, − 5, − 4, − 3, − 2, and − 1 days before the expected term of calving, calving day (0), and + 1, + 2, + 3, + 4, + 5, + 10, + 15, + 30 and + 60 days after the calving to measure thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), insulin, glucose, beta-hydroxybutyrate (BHB), bilirubin, total protein and albumin concentrations. Liver samples were biopsied at −7 ± 2 and +7 day relative to calving from both groups of cows to determine deiodinase (DIO) expressions and fat and glycogen content. Additionally, milk yield was monitored during the first 60 days of lactation. PTU successfully induced thyroid suppression by significantly reducing T3 and T4 concentrations and hepatic DIO1 expressions and caused PTU+ cows to have significantly higher insulin and glucose concentration in the precalving period. After calving, PTU+ cows had higher insulin and glucose concentration, liver glycogen content and overall milk production, lower BHB concentration, BCS loss, and liver fat deposits. Accordingly, cows treated with PTU have a more favourable energy balance and metabolic adaptation to early lactation.

The influence of calibration on bias in quality control and patient results for TSH on Vitros XT 7600 analyzer.

Thyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients' samples. In the period from October 2021 to August 2022 we looked at the QC results of ten 28-days' calibration time intervals and calculated relative bias compared to the mean. For each time interval the mean from three QC points before and after calibration was calculated. The average from 10 pre- and post-calibration means was calculated and the relative bias, pre- and post-calibration, was then calculated. We used 5 patient samples with low, normal and high TSH concentrations and calculated relative bias pre- and post-calibration. The allowed relative bias for TSH is ± 6.7%. At both QC levels, with the respective means of 5.14 mIU/L (coefficient of variation, CV% = 3.1%) and 27.80 mIU/L (CV% = 3.2%) had their respective relative bias - 8.2% and - 7.9%. The patient samples with low (0.586 mIU/L), normal (2.89 mIU/L and 5.19 mIU/L) and high (20.5 mIU/L and 39.8 mIU/L) TSH had - 4.1%, - 4.0%, - 3.5%, - 5.1% and - 4.1%, respectively. Even though the relative bias exceeded allowable criteria for the QC samples, this was not manifested on the patients' samples.

Thyroid gland dysfunction and keratoconus

Background: The association between keratoconus and thyroid gland dysfunction (TGD) remains controversial. We aimed to determine the frequency of keratoconus among patients with laboratory-confirmed, treatment-naive TGD compared with that of age- and sex-matched healthy controls. Moreover, we investigated the potential relationship between TGD and corneal topographic and tomographic parameters. Methods: This multicenter, cross-sectional study recruited individuals with treatment-naive, laboratory-confirmed TGD and sex- and age-matched healthy controls. Demographic and ophthalmic data of all participants were recorded. All participants underwent comprehensive ocular examinations and corneal tomography. Patterns of symmetric bowtie, asymmetric bowtie, asymmetric bowtie/superior steep, asymmetric bowtie/inferior steep, or asymmetric bowtie pattern with a skewed radial axis were documented if present. Furthermore, the maximum simulated keratometry value (Kmax), corneal thinnest thickness (CTT), and back elevation (BE) values were recorded. We measured the serum concentrations of thyroid-stimulating hormone (TSH) and thyroid hormones (free thyroxine [FT4] and free tri-iodothyronine [FT3]) using an immunoassay method. Results: We included 200 eyes of 200 individuals with TGD and 200 eyes of 200 healthy age- and sex-matched controls, with female predominance in both groups. The mean FT4 concentration was significantly higher and the TSH concentration was significantly lower in the TGD group than in the control group (both P < 0.0001), whereas the FT3 level was comparable between groups (P > 0.05). In the TGD group, the frequencies of hyperthyroidism and hypothyroidism were 190 (95%) and 10 (5%), respectively. We found significantly lower mean CTT, higher Kmax, and greater BE values with a significantly higher frequency of abnormal topographic patterns among eyes in the TGD group than in controls (all P < 0.05). The frequency of eyes with keratoconus was significantly higher in the TGD (7.5%) group than in the control (0.5%) group (P < 0.0001). Except for a statistically significant correlation of Kmax (r = - 0.23, P < 0.05) and CTT (r = + 0.15, P < 0.05) with TSH level in the TGD group, no significant correlation was found between corneal characteristics and thyroid profile in either group (all P > 0.05). Conclusions: We observed a higher frequency of keratoconus, with female predominance, in the TGD group. TGD was associated with significant changes in certain corneal topographic and tomographic parameters. Compared with healthy controls, individuals with TGD demonstrated increased Kmax and BE values with more corneal thinning, highlighting the potential association between keratoconus and TGD. However, further large-scale longitudinal studies are essential to confirm our findings.

Swellable Biopolymer Composite Microneedle Patch for Pain-Free Collection of Interstitial Fluid to Analyze Multiple Biomolecules.

Sampling of interstitial fluid (ISF) using microneedle (MN) patch offers a pain-free minimally invasive alternative to syringe needle-based blood sample collection. However, there is a challenge in the development of MN patch that provides swelling behavior with sufficient mechanical strength for skin penetration. Here, we report fabrication of MN patch made of biopolymer composite containing iota-carrageenan, gelatin, and polyethylene glycol. Calcium chloride was used as a crosslinker to improve mechanical strength. MN patch was characterized for integrity, swelling behavior, mechanical strength, aspiration of fluid from agarose gel, and the excised porcine ear skin. An array of 361 MNs was able to aspirate 36 ± 5 and 14 ± 1 μL fluid after application in agarose gel matrix and the ex vivo porcine skin model, respectively. MN patch applied in vivo rat model for 30 min resulted in the collection of ISF containing 267 ± 128 mg/dL, 24 ± 13 mg/dL, and 0.6 ± 0.4 mIU/mL of glucose, uric acid and thyroid stimulating hormone (TSH), respectively. The concentration of glucose, uric acid, and TSH in rat blood was found to be 199 ± 47 mg/dL, 8.4 ± 6 mg/dL, and 1.1 ± 0.6 mIU/mL at the same time. Furthermore, MN patch applied on the forearm of 10 healthy human volunteers for 30 min was able to aspirate 32 ± 14 μL of ISF. The concentration of glucose, uric acid, and TSH determined from ISF samples of human volunteers was 64 ± 25 mg/dL, 4.2 ± 4.1 mg/dL, and 0.16 ± 0.08 mIU/mL, respectively. The visual analogue scale (VAS) pain score after MN application was lower compared with hypodermic syringe needle insertion. Taken together, biopolymer composite-based swellable MN patch can be developed for collection of ISF for simultaneous determination of multiple biomolecules in a minimally invasive manner.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

Thyroid function tests in healthy kittens aged between 2 and 16 weeks.

This study aimed to determine thyroid hormone concentrations in a cohort of healthy kittens due to the paucity of information in the literature, and the potential for congenital hypothyroidism (CH) to contribute to fading kitten syndrome (FKS). The serum concentrations of total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3) and thyroid-stimulating hormone (TSH) were measured in 19 healthy kittens aged 2-16 weeks. Mean TT4, fT4, TT3 and fT3 concentrations significantly differed across age groups. Mean TT4 and fT4 concentrations peaked at 6 and 5 weeks of age, respectively. The TT4 concentration exceeded the adult cat reference interval (ACRI) in 54% (32/59) of samples at week 6, with the highest TT4 concentration being 7.1 µg/dl (91 nmol/l). Mean TT3 and fT3 concentrations also peaked at 6 weeks of age. Mean TT3 concentration started below the ACRI until 4 weeks of age, after which it remained within the ACRI. The mean fT3 concentration was within the ACRI at all ages. The mean TSH concentration did not differ across age groups and remained within the ACRI in nearly 100% of samples. Peak TT4, fT4, TT3 and fT3 concentrations in healthy kittens at 5 and 6 weeks of age are likely due to changes in the maternal transfer of thyroid hormones after weaning and organ system development. Knowing healthy neonatal and pediatric thyroid hormone concentrations in a cohort of kittens might help a veterinarian interpret thyroid hormone levels when trying to rule out CH in a kitten with FKS.

Exposure to PM2.5 and its constituents in relation to thyroid function of pregnant women: Separate and mixture analyses

The relationships between exposure to PM2.5 and its constituents and thyroid hormone (TH) levels in pregnant women are still uncertain, particularly regarding the impact of mixed exposure to PM2.5 constituents on thyroid function during pregnancy. This study aimed to investigate the individual and mixed effect of PM2.5 and its constituents on TH levels during pregnancy. Fluorescence and chemiluminescence immunoassays were utilized to measure serum concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in pregnant women participating in the Fujian Birth Cohort Study (FJBCS). PM2.5 and its constituents were obtained from the ChinaHighAirPollutants dataset. Generalized linear regression model and mixture analysis were applied to explore the individual and mixed effect of PM2.5 and its constituents on TH levels. 13711 participants from the FJBCS were taken into the final analysis. In the context of separate exposure, an increase of one interquartile range (IQR) in PM2.5 exposure during the 1st trimester, 2nd trimester, and entire pregnancy was associated with a decrease of −0.042 (−0.050, −0.034), −0.017 (−0.026, −0.009), and −0.011 (−0.017, −0.004) in FT4 level, respectively. As well, significant negative associations were observed between FT4 level and PM2.5 constituents. Additionally, PM2.5 and its constituents were in relation to an increased risk of hypothyroxinemia in pregnant women. It is noteworthy that, in the context of mixed exposure, the weighted quantile sum regression (WQS) indices were significantly associated with both FT4 level (1st trimester: −0.031 (−0.036, −0.026); 2nd trimester: −0.026 (−0.030, −0.023); whole pregnancy: −0.024 (−0.028, −0.020)) and hypothyroxinemia risk (1st trimester: 1.552 (1.312, 1.821); 2nd trimester: 1.453 (1.194, 1.691); whole pregnancy: 1.402 (1.152, 1.713)). PM2.5 and its chemical constituents may affect thyroid function in pregnant women individually and in combination, with the effect observed during early gestational exposure being most pronounced.

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.

Objective: To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. Methods: This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon signed ranks tests and generalized estimated equations to assess effects on thyroid and metabolic markers, and receiver operating characteristics curves to predict optimal dose. Results: Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day. Thyrotropin concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Conclusion: Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans.

Associations of the AVPR1A RS1 Microsatellite Locus with the Level of Hormones of the Anterior Pituitary Gland and Personality Traits.

The arginine vasopressin receptor gene (AVPR1A) is one of the genes affecting mental processes. The aim of this study was to search for associations of microsatellite locus RS1, which is related to the AVPR1A expression level, with the level of hormones of the anterior pituitary gland and personality traits. The study sample included Yakut men aged 18-26years (n = 121). The analysis of RS1 locus was carried out using the PCR method and sequencing of the primary nucleotide sequence. Serum hormonal levels of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin were determined by the time-resolved fluorescence immunoassay (DELFIA), plasma adrenocorticotropic hormone (ACTH) levels were determined by enzyme-linked immunosorbent assay (ELISA). In the Yakut population "short" (S) alleles of the AVPR1A RS1 locus containing ≤ 10 repeats (63%) and the corresponding SS genotypes (44.6%) were more frequent, while individuals with "long" (LL) and "heterozygous" (SL) genotypes accounted for 18.2 and 37.2%, respectively. The range of concentrations of ACTH and TSH in the group of SS genotype carriers was significantly lower than that observed in the group of LL genotype carriers (p = 0.042 and p = 0.048, respectively); the LH level was significantly higher (p = 0.029). The trend towards higher neuroticism in SS genotype carriers compared to the individuals with LL genotypes (p = 0.05) is revealed. The results obtained indicate the modulating effect of genetic variants of the AVPR1A gene on the level of anterior pituitary hormones, which could slightly affect the level of neuroticism in humans.

Changes in the level of immune checkpoints in patients with various forms of autoimmune thyroiditis

Background. Autoimmune thyroiditis (AIT) affects more than 5 % of the world’s population.The aim. To determine the level of sPD-1, sPD-L1, sCTLA-4 and sB7.2 molecules in individuals suffering from various forms of autoimmune thyroiditis.Methods. The study included 31 individuals aged 18 to 40 years. They were divided into four groups: group I – healthy individuals (n = 10); group II – carriers of antibodies to thyroid peroxidase (n = 11); group III – individuals with AIT accompanied with subclinical form of hypothyroidism (n = 6); group IV – individuals with AIT complicated by compensated hypothyroidism (n = 4). Venous blood was collected to determine the level of antibodies to thyroid peroxidase using enzyme immunoassay, the concentration of thyroid stimulating hormone and free thyroxine – using chemiluminescence immunoassay, and the levels of sPD-1, sPD-1L, sCTLA-4, and sB7.2 – using flow cytofluorometry. Statistical processing was performed using the Kruskal – Wallis one-way analysis of variance.Results. When comparing the level of sPD-1L in groups I (54.1 (28.7; 67.6) pg/ml) and II (4.36 (2.36; 18.0) pg/ml), the decreased in this indicator was 91.94 % (p = 0.001). When comparing the sPD-1 level in the group of healthy individuals (16.6 (13.6; 37.2) pg/ml) and group IV (7.28 (5.18; 11.1) pg/ml), werecorded a decrease of 56.14 % (p = 0.001). The sB7.2 concentration decreased by 65.03 % in group II (16.4 (15.6; 32.7) pg/ml) compared to the control group (46.9 (39.3; 54.4) pg/ml) (p = 0.001). In group III, the sCTLA-4 level was 3.22 (3.06; 3.33) pg/ml and decreased by 88.66% compared to the control group (p = 0.001).Conclusion. The development of autoimmune thyroiditis is accompanied with the decrease in the concentration of sPD-1, sPD-1L, sCTLA-4 and sB7.2.

Autoimmune Hypothyroidism Associated with Helicobacter Pylori Infection

Objective: The study aimed to investigate the correlation between Helicobacter pylori (H. pylori) and thyroid autoimmunity. Material and Methods: To demonstrate the possible correlation between H. pylori infection and autoimmune hypothyroidism, 200 individuals were enrolled in this research (100 patients with active H. pylori infection and 100 healthy controls). All of them were tested for serum levels of thyroid hormones, thyroid stimulating hormone (TSH), and autoantibodies, as well as Helicobacter pylori-Immunoglobulin G (H. pylori-IgG) and cytotoxin-associated gene A-Immunoglobulin G (cagA-IgG) antibodies. Results: The study found that H. pylori infection was associated with higher levels of TSH, thyroperoxidase and thyroglobulin (TPO and TG) (p-value&lt;0.000, 0.001 and 0.006, respectively) and a significant decrease in the levels of free-thyroid hormone (FT3 and FT4) (p-values=0.008 and 0.007 respectively) in patients compared with the control group. Moreover, using Pearson’s correlation tests, significant proportional correlations were found between H. pylori IgG and TSH (r=0.302, p-value=0.001), and a significant negative correlation was found between anti-H. pylori-IgG and with FT3 and FT4 (r=-0.261, p-value=0.003 and r=-0.260, p-value=0.003, respectively). Moreover, Spearman’s correlation results showed that H. pylori IgG was positively linked to TPO (r=0.531, p-value&lt;0.001) and TG (r=0.320, p-value=0.001). Conclusion: The current investigation found that H. pylori infection was linked to higher concentrations of thyroid autoantibody and TSH and lower levels of thyroid hormones, suggesting that the bacterium may play a role in the development of subclinical autoimmune hypothyroidism.

Age-specific reference intervals for TSH and FT4 to optimize diagnosis of thyroid disease.

Background Thyroid-stimulating hormone (TSH) and subsequent free thyroxine (FT4) concentrations outside the reference interval (RI) are used to diagnose thyroid diseases. Most laboratories do not provide age-specific RIs for TSH and FT4 beyond childhood, although TSH concentrations vary with age. Therefore, we aimed to establish TSH and FT4 age-specific RIs throughout life and aimed to determine whether using these RIs would result in reclassification of thyroid disease diagnoses in adults. Methods This multicenter retrospective cross-sectional study used big data to determine indirect RIs for TSH and FT4. These RIs were determined by TMC and refineR-analysis, respectively, using four different immunoassay platforms (Roche, Abbott, Siemens, Beckman Coulter). Retrospective data (2008-2022) from 13 Dutch laboratories for general practitioners and local hospitals were used. RIs were evaluated per manufacturer. Age groups were established from 2-20 years by 2-year categories and decade categories between 20 and 100 years. Results We included totally 7.6 million TSH and 2.2 million FT4 requests. TSH upper reference limits (URLs) and FT4 lower reference limits (LRLs) were higher in early childhood and decreased towards adulthood. In adulthood, TSH URLs increased from 60 years in men, and from 50 years in women, while FT4 URLs increased from 70 years onwards. Using adult age-specific RIs resulted in a decrease in diagnoses of subclinical and overt hypothyroidism in women above 50 and men above 60 years in our Roche dataset. Conclusion This study stressed the known importance of using age-specific RIs for TSH and FT4 in children. This study also showed the clinical relevance of using age-specific RIs for TSH in adulthood to reduce diagnoses of subclinical hypothyroidism in older persons. Therefore, implementation of adult TSH age-specific RIs should be strongly considered. Data is less uniform regarding FT4 age-specific RIs and more research should be performed before implementing these in clinical practice.

Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary-Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats.

Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary-thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats.

Iodine supply and thyroid function in women with gestational diabetes mellitus: a cohort study.

Maternal urinary iodine concentration and blood neonatal thyroid-stimulating hormone (TSH) concentration reflect iodine status in pregnancy and serve as markers of iodine deficiency. As dietary measures in gestational diabetes mellitus (GDM) could affect iodine intake, our study aimed to investigate iodine supply in women with GDM compared to healthy pregnant women and to evaluate its relationship to maternal and neonatal thyroid function. Urinary iodine concentration (UIC) and serum TSH, free thyroxine (FT4), and autoantibodies against thyroid peroxidase (TPOAb) were analyzed in 195 women with GDM and 88 healthy pregnant women in the second trimester. Subsequently, neonatal TSH concentrations measured 72 h after delivery in a subgroup of 154 newborns (115 of mothers with GDM and 39 controls) from the national register were analyzed. Median UIC was significantly lower in women with GDM compared to controls (89.50 µg/L vs. 150.05 µg/L; P < 0.001). Optimal iodine intake was found only in nine women with GDM (4.6%) and 33 healthy pregnant women (37.5%) (P < 0.001). Most pregnant women with GDM (88.7%) compared to one half of controls (50%) had iodine deficiency (P < 0.001). Although serum TSH and the prevalence of hypothyroidism (TSH > 4.0 mIU/L) were not different in both groups, hypothyroxinaemia was more prevalent in GDM compared to controls (12.3% vs 3.4%, P = 0.032). Consistently, neonatal TSH > 5.0 mIU/L indicating iodine deficiency, was found in 6 (5.2%) newborns of women with GDM as compared to none in controls. In women with GDM, the prevalence of perinatal complications was significantly lower in those who were taking dietary iodine supplements compared to those who were not (3/39 (7.69%) vs 46/156 (28.85%), P <0.001). In the multiple logistic and linear regression models in women with GDM, hypothyroxinaemia was associated with preterm births, and a negative association of serum FT4 and HbA1c was found. Iodine deficiency in pregnancy was more prevalent among women with GDM compared to healthy pregnant controls. Serum FT4 negatively correlated with HbA1c, and hypothyroxinaemia was associated with preterm births in women with GDM. Conversely, women with GDM who used dietary iodine supplements had a lower risk of perinatal complications.

The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis.

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.

The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism.

Metformin inhibits enhanced secretion of anterior pituitary hormones. Its impact on prolactin and gonadotropin concentrations is absent in individuals with hypovitaminosis D. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism, which were matched for age, thyroid-stimulating hormone (TSH) concentration, and insulin sensitivity: untreated women with vitamin D deficiency/insufficiency (group A), women effectively supplemented with exogenous calciferol (group B), and untreated women with normal 25-hydroxyvitamin D concentrations (25OHD) (group C). Owing to concomitant type 2 diabetes or prediabetes, all subjects were treated with metformin. Concentrations of 25OHD, TSH, total and free thyroid hormones, glucose, insulin, glycated hemoglobin (HbA1c), prolactin, and peripheral markers of thyroid hormone action were assayed before metformin treatment and six months later. Based on hormone concentration, structure parameters of thyroid homeostasis were calculated. Except for 25OHD concentrations, there were no between-group differences in baseline values of the measured variables. Metformin reduced glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and HbA1c in all study group, but these effects were less pronounced in group A than in the remaining groups. The reduction in TSH and Jostel's index was observed only in groups B and C, and its degree correlated with baseline TSH concentrations, baseline 25OHD concentrations, and the degree of improvement in HOMA1-IR. The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.

Association Between Long-Term Exposure to Environmental Fine Particulate Matter and the Prevalence of Thyroid Disorders: A National Cross-Sectional Study in China.

Background: Exposure to particles with an aerodynamic diameter of ≤2.5 μm (PM2.5) is associated with the occurrence of thyroid dysfunction among pregnant women and neonates, but it is not known if this association occurs in the general population. We aimed to determine the association of prolonged exposure to PM2.5 with the prevalence of thyroid disorders among adults in China. Methods: A nationally representative cross-sectional study of thyroid disorders, iodine status, and diabetes status was carried out in all 31 provinces across China from 2015 to 2017. In total, 73,900 adults aged 18 years and older were included. Serum concentrations of thyroid hormones, thyrotropin, and thyroid antibodies and the urine iodine concentration were measured. The environmental concentration of PM2.5 for each participant's residential address at a spatial resolution of 1 × 1 km was estimated. Results: The average long-term exposure to PM2.5 at residential addresses was 66.41 μg/m3, ranging from 17.58 μg/m3 to 120.40 μg/m3. Compared with that of individuals with lower exposure levels, the prevalence of thyroid diseases such as autoimmune thyroiditis and subclinical hypothyroidism was greater in those with PM2.5 concentrations within the third quartile range (60.18 to 73.78 μg/m3). Compared with those in the first quartile (17.58 to 46.38 μg/m3), participants in the highest PM2.5 quartile (73.78 to 120.40 μg/m3) presented an increased risk of overt hypothyroidism (OR 1.23 [CI 0.94-1.61]), subclinical hypothyroidism (1.10 [1.01-1.21]), autoimmune thyroiditis (1.09 [1.00-1.18]), and thyroglobulin antibody positivity (1.17 [1.07-1.29]). However, there was no association between PM2.5 exposure and overt hyperthyroidism, subclinical hyperthyroidism, Graves' disease, or thyroid peroxidase antibody positivity (p > 0.05). Each 10 μg/m³ increase in the PM2.5 concentration was associated with an increased risk of overt hypothyroidism (OR 1.05 [1.00-1.11]), subclinical hypothyroidism (1.02 [1.00-1.03]), and thyroglobulin antibody positivity (1.02 [1.00-1.04]). Furthermore, a nearly linear exposure-response relationship was observed between long-term PM2.5 exposure and thyroglobulin antibody positivity. Conclusions: PM2.5 exposure was associated with thyroid disorders among Chinese adults. A dose-response relationship between PM2.5 exposure and autoimmune thyroiditis, as well as thyroglobulin antibody positivity, was also observed.

Features of the functioning of the hypothalamic-pituitary-thyroid axis in mice with Lewis carcinoma on the background of induced hyperthyroidism

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory. The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT). Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum. Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted. Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

Association of maternal mild hypothyroidism in the first and third trimesters with obstetric and perinatal outcomes: a prospective cohort study

BackgroundMild hypothyroidism, including subclinical hypothyroidism (SCH) and isolated maternal hypothyroxinemia (IMH), is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy. ObjectiveTo evaluate the impact of SCH and IMH in the first and third trimesters, respectively, on obstetric and perinatal outcomes. Study DesignThis large prospective study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai. 52,027 pregnant women who underwent the first-trimester antenatal screening at IPMCH were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal SCH and IMH in the first trimester on pregnancy outcomes, participants were divided into three groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n= 33,130), first-trimester SCH group (n= 884), and first-trimester IMH group (n= 846). Then, to evaluate the impact of maternal SCH and IMH in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into three groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n= 30,776), third-trimester SCH group (n= 562), and third-trimester IMH group (n= 578). Obstetric and perinatal outcomes, including preterm birth (PTB), preeclampsia, gestational hypertension, gestational diabetes mellitus (GDM), large for gestational age (LGA), small for gestational age, macrosomia, cesarean section, and fetal demise were measured and compared between those in either SCH/IMH group and euthyroid group. Binary logistic regression was used to assess the association of SCH or IMH with these outcomes. Results34,860 pregnant women who had first (weeks 8–14) and third trimester (weeks 30–35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal SCH in the first trimester was linked to a lower risk of GDM (aOR 0.64, 95% CI 0.50–0.82) compared with the euthyroid group. However, third-trimester SCH is associated with heightened rates of PTB (aOR 1.56, 95%CI 1.10–2.20), preeclampsia (aOR 2.23, 95%CI 1.44–3.45), and fetal demise (aOR 7.00, 95%CI 2.07–23.66) compared with the euthyroid group. IMH in the first trimester increased risks of preeclampsia (aOR 2.14, 95% CI 1.53–3.02), GDM (aOR 1.45, 95%CI 1.21–1.73), LGA (aOR 1.64, 95%CI 1.41–1.91), macrosomia (aOR 1.85, 95%CI 1.49–2.31) and cesarean section (aOR 1.35, 95%CI 1.06–1.74), while IMH in the third trimester increased risks of preeclampsia (aOR 2.85, 95%CI 1.97–4.12), LGA (aOR 1.49, 95%CI 1.23–1.81) and macrosomia (aOR 1.60, 95%CI 1.20–2.13) compared with the euthyroid group. ConclusionThis study indicates that while first-trimester SCH did not elevate the risk for adverse pregnancy outcomes, third-trimester SCH was linked to several adverse pregnancy outcomes. IMH in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.