Increased thyroid hormone sensitivity is correlated with visceral obesity in patients with type 2 diabetes.

OBJECTIVE: The study aimed to assess whether thyroid hormone (TH) sensitivity is related to visceral fat area (VFA) and visceral obesity in euthyroid subjects with type 2 diabetes (T2D). METHODS: 750 euthyroid patients with T2D were enrolled. A VFA of 80 cm2 or more was considered visceral obesity. Central TH sensitivity was conducted using thyrotrophic thyroxine resistance index (TT4RI), thyrotropin index (TSHI), and thyroid feedback quantile-based index (TFQI). Free triiodothyronine to free thyroxine (FT3/FT4) was utilized for assessing peripheral TH sensitivity. RESULTS: The subjects had a mean age of 51.5 ± 11.1 years, and 540 (72.0%) of them were men. In multivariable regression analyses, there was a positive correlation of FT3/FT4 tertile with visceral obesity, after full adjustment for confounding variables (P < 0.05). The middle and highest FT3/FT4 tertiles were correlated with a 134% [95% CI (1.24, 4.44)] and 98% [95% CI (1.04, 3.78)] higher prevalence of visceral obesity than the lowest tertile, respectively. Conversely, elevated TFQI levels were linked to a decreased prevalence of visceral obesity. Stratified analysis revealed that these associations were particularly pronounced in participants who are neither overweight nor obese and those aged less than 60 years (all P < 0.05). CONCLUSIONS: Higher TH sensitivity is correlated with visceral obesity and elevated VFA in euthyroid patients with T2D, particularly among those younger than 60 years and individuals who are neither overweight nor obese.

FT4 is a novel indicator for risk assessment of severe hypocalcemia following parathyroidectomy.

OBJECTIVE: To analyze the risk factors associated with the development of severe hypocalcemia (SH) in patients who have undergone parathyroidectomy (PTX). METHODS: This research involved patients with chronic kidney disease-secondary hyperparathyroidism who underwent PTX between June 1, 2021, and May 31, 2023. SH was characterized by a serum total calcium (tCa) level below 1.8 mmol/L. This study aimed to analyze differences in preoperative laboratory findings and clinical manifestations between patients with and without SH. Logistic regression analysis was used to identify potential risk factors associated with the development of SH. RESULTS: The incidence of SH was 23% (n = 176). Significant differences were observed in free thyroxine (FT4), free triiodothyronine, alanine aminotransferase, osteocalcin, tCa, alkaline phosphatase (ALP), C-terminal cross-linked telopeptide of type I collagen, and parathyroid hormone between the SH and non-SH groups. The three independent risk factors for SH were tCa [odds ratio (OR) 0.063, 95% confidence interval (95% CI) 0.006-0.663], ALP (OR 1.003, 95% CI 1.001-1.005), and FT4 (OR 0.439, 95%CI 0.310-0.621). The area under the curve, sensitivity, specificity, and overall accuracy of this model were 0.904 (95% CI 0.856-0.952), 46.3%(95% CI 32.0%-61.3%), 94.8% (95% CI 89.7%-97.5%), and 83.5% (95% CI 77.3%-88.3%), respectively. CONCLUSION: The preoperative level of FT4 plays a crucial role in predicting the risk of SH after PTX. The combined FT4-ALP-tCa model demonstrates the ability to predict SH risk, providing valuable insights for customizing calcium supplementation strategies and improving clinical decision-making.

Doping of Mn2+ ion into boron quantum dots with enhanced fluorescence properties for sensing of L-thyroxine biomarker and bioimaging applications.

L-thyroxine serves as a primary biomarker for diagnosing hypothyroidism and it is also utilized in hormone replacement therapy. Regular assessment of thyroxine levels is crucial for preventing health issues in hypothyroid patients, suggesting the requirement of a facile analytical tool for the detection of L-thyroxine. In this work, a straightforward and efficient synthetic method is introduced for in-situ preparation of Mn2+-doped boron quantum dots (Mn2+@B-QDs) derived from boron powder through a solvothermal reaction. The introduction of Mn2+ ion into B-QDs not only enhances fluorescence efficiency but also provides favorable sites within the QDs, expanding their potential applications in analytical chemistry. The blue fluorescent Mn2+ @B-QDs exhibited excellent performance for the selective recognition of L-thyroxine via a dynamic quenching mechanism. Under ideal conditions, a good linear relation was observed between the fluorescence emission intensity ratio of Mn2+@B-QDs and the concentration of L-thyroxine in the range of 0.125-5 µM, with a lower detection limit of 59.86 nM. The Mn2+@B-QDs exhibited the negligible cytotoxicity against A549 lung cancer cell lines and demonstrated good biocompatibility toward Saccharomyces cerevisiae cells.

Blood levels of zearalenone, thyroid-stimulating hormone, and thyroid hormones in patients with colorectal cancer.

Mycotoxins are secondary metabolites produced by various species of mold fungi commonly found in plant materials. Zearalenone (ZEN) adversely affects the endocrine system. This study aimed to determine whether thyroid-stimulating hormone (TSH), procalcitonin (PCT), free triiodothyronine (fT3), and free thyroxine (fT4) levels are altered during natural zearalenone mycotoxicosis in patients diagnosed with sigmoid colon cancer (SCC) or colorectal cancer (CRC). A study was conducted on women and men diagnosed with SCC or CRC accompanied by the presence or absence (Patients Without ZEN - PWZ group) of ZEN in the blood. The PWZ group consisted of 17 patients with symptoms of SCC and CRC in whom ZEN and its metabolites were not detected in peripheral blood. The experimental (empirical) groups included a total of 16 SCC and CRC patients who tested positive for ZEN, but not its metabolites. TSH values in both sexes were within the upper limit of the reference range (0.27 - 4.2 µIU/mL) adopted by the hospital laboratory and corresponded to the upper second tertile and the lower third tertile. PCT values demonstrated that SCC and CRC were accompanied by a systemic or local bacterial infection. All mean values of fT3 were in the middle of the reference range, and the mean values of fT4 were within the upper reference limit. The fT3/fT4 prognostic marker was somewhat above the cut-off point of 0.22. These results indicate that in postmenopausal women and andropausal men who were diagnosed with SCC and CRC and were exposed to food-borne ZEN, higher values of the prognostic marker (fT3/fT4) were associated with an unfavorable prognosis. The study also revealed that the more distal the neoplastic lesions in the colon, the higher the percentage of both thyroid hormones, regardless of the patient's sex. The presence of ZEN in the diet alters thyroid activity in patients diagnosed with SCC and CRC.

Edward Calvin Kendall: A Pioneer in Biochemistry and Endocrinology.

Edward Calvin Kendall was a distinguished American biochemist known for pioneering research on adrenal cortex hormones, notably cortisone. This review article examines Kendall's life, career, and key scientific contributions, including his groundbreaking work on thyroid hormones and corticosteroids. The discussion emphasizes Kendall's role in advancing biochemical research and his lasting influence on physiology and medicine. By analyzing primary sources and historical accounts, this article offers a thorough overview of Kendall's impact on biochemistry and endocrinology.

Changes in Central Sensitivity to Thyroid Hormones vs. Urine Iodine during Pregnancy.

INTRODUCTION/AIM: Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose-response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake. MATERIALS AND METHODS: One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson's correlation was used to assess the TFQI versus UI. RESULTS: The mean TFQI index ranged from -0.060 (second trimester) to -0.053 (two months postpartum), while the corresponding UI was 137 and 165 µg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: -0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 µg/L, in the first and the second trimesters of pregnancy, respectively. DISCUSSION: The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis' function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

A Randomized Clinical Trial Comparing 2 Levothyroxine Regimens During Ramadan Fasting in Thyroidectomized Patients.

Context: For Muslim patients on levothyroxine (L-T4) therapy, the best approach for L-T4 intake during Ramadan fasting remains unclear. Objective: We compared 2 practical approaches for L-T4 intake during Ramadan. Methods: We randomly assigned 69 patients (21 males, 48 females, median age 44 years) with differentiated thyroid cancer (DTC) who underwent thyroidectomy in the past and are on stable LT4 doses to 2 arms. Arm A (33 patients) ingested their pre-Ramadan L-T4 dose at the evening meal and ate immediately. Arm B (36 patients) increased their pre-Ramadan dose by 25 µg if their regular L-T4 dose was ≤150 µg/day or by 50 µg if their pre-Ramadan dose was >150 µg/day and ate immediately. Results: At the beginning of Ramadan (baseline), the median thyrotropin (TSH) level and the numbers of patients in euthyroidism, subclinical hyperthyroidism (Shyper), or subclinical hypothyroidism (Shypo) were comparable between the 2 arms (P = .69 and P = .65, respectively). At the end of Ramadan, in arm A there were 17 (51.5%), 3 (9.1%), and 13 (39.4%) patients in euthyroidism, Shyper, and Shypo compared with 17 (47.2%), 14 (38.9%), and 5 (13.9%) patients, respectively, in arm B (P = .005). The mean ± SD TSH levels in arms A and B at the end of Ramadan were 5.6 ± 6.0 mU/L and 1.67 ± 2.6 mU/L, respectively (P = .0001). Conclusion: No overt thyroid dysfunction developed but there were more cases of Shypo in arm A and Shyper in arm B. Arm B achieved desirable levels of TSH (normal or slightly suppressed) in 86% of cases and might be a preferable approach, especially for patients who need TSH suppression (eg, DTC).

Thyroid hormone receptor-ß analogs for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH).

The association between suboptimal thyroid function ((sub)clinical hypothyroidism or low normal thyroid function) and the metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) is clearly established. Furthermore, in MASLD, thyroid hormones have low intracellular concentrations and the activation of the thyroid hormone receptor (THR) is reduced. Administration of thyroid hormone has been shown to reduce liver triglycerides by stimulating fatty acid disposal through lipophagy and beta-oxidation, and to lower LDL-cholesterol. As thyroid hormone exerts it's effects in many different organs, including heart and bone, several drug candidates have been developed acting as selective thyromimetics for the THR-ß nuclear receptor with potent and targeted liver actions. Importantly, these compounds have reduced affinity for the THR-α nuclear receptor and tissue distribution profiles that differ from endogenous thyroid hormones thereby reducing unwanted cardiovascular side effects. The most advanced compound, resmetirom, is an oral drug that demonstrated, in a large phase 3 trial in MASH patients, the ability to remove liver fat, reduce aminotransferase levels and improve atherogenic dyslipidemia with a good tolerability profile. This translated into histological improvement that led to accelerated approval of this drug for active fibrotic steatohepatitis, a milestone achievement as a first MASH drug.

Current status of the thyroid hormone measurement items in patients receiving levothyroxine monotherapy by the management based on the thyroid tissue volume.

We and other investigators reported that mild TSH suppression with levothyroxine (LT4) was needed to achieve normal free triiodothyronine (FT3) levels and metabolic euthyroid state in athyreotic patients. Consequently, management methods based on thyroid tissue volume have been implemented for patients receiving LT4 at the Kuma Hospital. This retrospective study examined the composition of the thyroid hormone measurement items (serum-free thyroxine [FT4], FT3, and FT4 + FT3) in patients receiving LT4 monotherapy. According to the etiology of hypothyroidism, 36% of the 25,523 patients included in this study underwent total thyroidectomy (TT). Thirteen percent and 14% had undergone 131I treatment for hyperthyroidism (RIT) and partial thyroidectomy (PT), respectively. Moreover, 37% of patients had received non-invasive treatment (NIT). The proportion of patients who underwent only FT3 measurements was higher (TT, 93%; RIT, 61%) in the first two groups, whereas the proportion of patients who underwent only FT4 measurements was higher (PT, 50%; NIT, 65%) in the remaining two groups. Only FT3 measurements were performed in 58% of patients. Only FT4 measurements were performed in 34% of patients. The serum TSH levels were suppressed in nearly half of the patients (46%). Thus, FT3 was the major thyroid hormone measured in patients receiving LT4 treatment, and the serum TSH levels were suppressed in nearly half of the patients. This may be attributed to the management guidelines at our hospital, a specialized facility for thyroid disease, wherein half of the patients present are athyreotic or have atrophic thyroid glands after TT or RIT.

Regulatory Effects of 5-Day Oral and Intraperitoneal Administration of a Thienopyrimidine Derivative on the Thyroid Status in Rats.

In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland. During long-term administration, compound TPY3m stimulates the production of thyroid hormones without weakening the activity of the thyroid axis. Thus, TPY3m is a prototype of drugs for correcting thyroid hormone deficiency.

Establishment of a Quenchbody-based L-thyroxine detection method and its comparison with ELISA systems.

The quantification of L-thyroxine (T4) is crucial for regulating metabolism, diagnosing diseases, and monitoring the efficacy of T4 replacement therapy. However, because T4 is a hapten biomarker with a molecular weight of 777 g/mol, conventional immunoassay approaches, including Western blotting and some types of ELISA, have limited accuracy in the quantification of small molecules, including T4. Furthermore, these methods are time-consuming and involve multiple incubation and reaction steps. Therefore, a novel immunoassay method is required for simple and rapid on-site detection of T4. In this study, we expressed a recombinant anti-T4 single-chain variable fragment (scFv) in soluble form using Escherichia coli. The scFv exhibited high T4-binding efficiency, and T4 concentration-dependent titration curves indicated that the sandwich ELISA could detect T4 in the nanogram range. We labeled the scFv using a fluorescent dye for a Quenchbody (Q-body)-based one-pot immunoassay, which yielded a T4 concentration-dependent fluorescent response in 3 min. A comparison of the Q-body-based T4 detection system with ELISA-based methods demonstrated that the ELISA system was more sensitive but the Q-body assay was more rapid. Therefore, both ELISA and Q-body systems can be used depending on the experimental purpose, with the newly developed anti-T4 Q-body system being applicable for convenient in situ immunoassay of T4.

Olfaction and thyroid hormones in patients with subjective cognitive decline, non-amnestic and amnestic mild cognitive impairment.

BACKGROUND: Thyroid hormones may affect olfaction in different stages of cognitive impairment: subjective cognitive decline (SCD), non-amnestic (naMCI) and amnestic mild cognitive impairment (aMCI). Additionally, biometric parameters, depression, and neuropsychological performance are considered as possible influencing factors. DESIGN AND PATIENTS: A retrospective single-center data analysis was conducted during the observation period 2001-2023, with n = 495 (52.3% female) SCD, naMCI and aMCI subjects, aged ≥50 years, at the General Hospital of Vienna. MEASUREMENTS: The criterion olfactory function was objectively measured by Sniffin' Sticks© odor identification and subjectively through the Assessment of Self-Reported Olfactory Functioning test. Serum thyroid hormone levels, mainly thyroid-stimulating hormone, as well as T3, T4, fT3, and fT4, were used to assess thyroid function. Statistical analyses using IBM SPSS® 29.0.0 covered adjusted multiple linear regression models with hierarchical blocks to predict olfactory performance considering ß­weights. RESULTS: Of the study participants, 4.2% had hypothyroidism and 2.4% had hyperthyroidism. The majority exhibited normal thyroid function. One third (33.5%; 95% confidence interval, CI 29.4-37.0%) were hyposmic. The results indicate no substantial association between thyroid and olfactory functions. Increasing age (ß = 0.20), lower performance in the Neuropsychological Test Battery Vienna (NTBV) dimensions verbal memory (ß = -0.33) and attention (ß = -0.12) appear to be risk factors for lower olfaction. A discrepancy between subjective and objective olfaction was found. CONCLUSION: Thyroid and olfactory functions had no substantial relationship. Higher fT4 correlated weakly with lower odor identification. Increasing age and decreased performance in two out of six NTBV dimensions are relevant prognostic factors for olfactory dysfunction.

When the Expected Becomes Unexpected: An Acute Presentation of Hypothyroidism.

Myxedema coma is an uncommon and life-threatening manifestation of severe hypothyroidism. Its occurrence in the pediatric population is exceptionally rare and can result from long-standing untreated hypothyroidism or nonadherence to treatment. Identifying this condition can be challenging because it requires a high level of clinical suspicion along with thyroid function testing. We present a 17-year-old female with a history of anxiety who had widespread nonspecific symptoms, including persistent bradycardia, which were found to be caused by hypothyroidism. Our goal is to raise awareness of the varied clinical manifestations of pediatric myxedema to promote early recognition and prompt medical interventions that can lead to better outcomes.

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.

Relationship of Thyroid Volume and Function with Ankle-Brachial Index, Toe-Brachial Index, and Toe Pressure in Euthyroid People Aged 18-65.

Background and Objectives: The interrelationship between thyroid function and the state of the cardiovascular system has been investigated both in preclinical and human studies. However, it remains unclear whether there is any association between thyroid hormones and features of subclinical cardiovascular dysfunction in euthyroid patients. Material and Methods: This study involved 45 people (females: 57.8%) with no thyroid disease who, during planned hospitalization, underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and measurement of ankle-brachial index (ABI) and toe-brachial index (TBI). People with signs of acute illness or a deterioration of their health were excluded. Results: Significant correlations were found between free triiodothyronine (FT3) and several parameters of both ABI (R = 0.347; p = 0.019 for the mean ABI taken from right side and left side values) and TBI (R = 0.396; p = 0.007 for the mean TBI taken from right side and left side values), as well as the maximal toe pressure (TP) taken from right side and left side values (R = 0.304; p = 0.045). Thyrotropin (TSH) was shown to be significantly correlated only with the maximal TBI value (taken from right side and left side values) (R = 0.318; p = 0.033), whereas free thyroxin (FT4) was shown to be significantly correlated only with the minimal TBI value (taken from right side and left side values) (R = 0.381; p = 0.01). Thyroid volume (TV) was shown to be correlated with TP (R = 0.4; p = 0.008 for the mean TP taken from right side and left side values) and some parameters of TBI value (R = 0.332; p = 0.028 for the mean TBI taken from right side and left side values), but no significant correlations were found between TVand ABI parameters. Patients with a mean ABI value ≤ 1.0 or a mean TBI value ≤ 0.75 have lower TSH, FT3, FT4, and TV than the rest of the study population, but the difference was statistically significant only for FT3. Conclusions: Even in a population of euthyroid patients with no diagnosed thyroid disease, there are some significant correlations between the volume and function of the thyroid gland and the selected features of subclinical cardiovascular dysfunction such as ABI and TBI.

Distinct transcriptional profiles in rat thyroid glands after developmental exposure to three in vitro thyroperoxidase inhibiting chemicals.

Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.

Refractory hypothyroidism in children: an overview.

Refractory hypothyroidism (RF) defined as raised serum levels of thyroid stimulating hormone (TSH) above upper limit of the reference range with or without the persistence of hypothyroid symptoms following a 6-week interval after the dosage was last increased to upper limits of dose per age. The most common cause of RH is inadequate compliance. In addition, diet, concomitant medication interactions, and gastrointestinal diseases can all result in l-thyroxine (LT4) malabsorption, which can cause RH. Moreover, weight gain, switching brands of LT4, poor storage of LT4, chronic liver disorders, cystic fibrosis, nephrotic syndrome, consumptive hypothyroidism, Addison's disease are significant contributors to RF in children. RH in children is frequently asymptomatic, when symptoms do occur, they are typically minor and resemble those of hypothyroidism. It is essential to identify RH early and treat its underlying cause in order to avoid overusing LT4, which can lead to cardiac and bone problems. Endocrinologists should handle children who they suspect of having RH methodically after making sure there is enough compliance. Searching for undiagnosed illnesses and/or other factors that can affect LT4 absorption could be part of this. We present this review after an extensive literature search and long-standing clinical experience. This review's objective is to shed light on the causes, clinical manifestations, investigations, and treatment of RH in children.

Hyperthyroidism keeps immunoglobulin levels but reduces milk fat and CD11b/c+ cells on early lactation.

Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T4 (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRß1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45+ and CD3+ cells and decreased CD11b/c+ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.

Age-Specific Reference Intervals for Thyroid-Stimulating Hormones and Free Thyroxine 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, and 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 to 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 were higher in early childhood and decreased toward adulthood. In adulthood, TSH URLs increased from 60 years in men, and from 50 years in women, while FT4 URLs increased from 70 years onward. 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 are less uniform regarding FT4 age-specific RIs and more research should be performed before implementing these in clinical practice.

Exploring the Effect of Thyroid Hormone on Serum Lipoprotein (a) Levels in Patients With Thyroid Hormone Dysfunction: A Systematic Review.

Genetic variations among people mainly determine the blood levels of lipoprotein (a) (Lp(a)), and it is relatively stable throughout one's lifetime. Nevertheless, there could still be other factors that control the Lp(a) level. Thyroid hormones are known to influence the serum lipid level by regulating the expression of key enzymes that are involved in lipid metabolism. Both hypo and hyperthyroidism are associated with changes in lipid levels. Even though thyroid hormone abnormalities have been shown to alter traditional lipid parameters like low-density lipoprotein (LDL-C), its influence on Lp(a) has not been established. This review aims to identify the relationship between Lp(a) and thyroid hormones by reviewing data from correlative studies and observing treatment-related Lp(a) level changes in thyroid disorders from interventional studies. We searched MEDLINE, Cochrane, and Google Scholar databases with predefined search criteria and search strategies for paper identification. Individual reviewers reviewed identified papers for selection. Finalized papers were reviewed for Lp(a) levels and their responses to treatment in patients with thyroid disorders to establish the relationship between Lp(a) and thyroid hormone. We concluded that the data were limited and sometimes contradicted one another to establish a clear relationship between Lp(a) and thyroid hormones. Even though correlative studies data showed strong indications that overt-hypothyroidism was associated with high Lp(a) levels, thyroid hormone replacement studies did not show any significant changes in Lp(a) levels compared to pre-treatment in patients with both overt-hypothyroidism and subclinical hypothyroidism. More clinical trials focusing on Lp(a) with longer periods of treatment and follow-up in thyroid patients are needed to establish the relationship between the two. The possibility of dose-related Lp(a) responses to thyroid hormone treatment should also be explored.