Serum T4 Concentrations Research Articles

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats

AbstractBackgroundHypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism‐like behavior of IMH offspring.MethodsThe animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid‐stimulating hormone (TSH) were detected using enzyme‐linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open‐field test, three‐chamber sociability test, and Morris water maze, to explore the autistic‐like behavior of 40‐day‐old offspring rats.ResultsThe ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly.ConclusionThe animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic‐like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

Effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.

Aromatase plays an important role in ovarian development, the normal progress of the menstrual cycle, and fertility status. Elevated aromatase activity is linked to obesity. There is a bidirectional relationship between obesity and thyroid function. Few studies have investigated the relationship between TSH and ovarian aromatase in obesity. Our aim was to investigate the effect of TSH on aromatase expression of ovarian granulosa cells in obese mice. Female mice pups were divided into an obesity group and a control group. Obese parameters and the time of pubertal onset were recorded. At the age of 5weeks, blood and tissues were obtained. Serum aromatase and hormone concentrations were measured using ELISA. The granulosa cells were isolated and exposed to variable concentrations (0μM, 1μM, 10μM, 100μM) of TSH. The expression of CYP19A1 mRNA and protein were assessed via RT-qPCR and western blot. In female mice, body weight, Lee's obesity index, and serum levels of E2, aromatase, and TSH were significantly higher in the obesity group compared to the control group, whereas the time of pubertal onset and serum T3 and T4 concentrations were significantly lower (all P < 0.001). In granulosa cells, the expression of CYP19A1 mRNA in the obesity group was lower than that in the control group at 1μM and 100μM concentrations of TSH (both P < 0.001). The expression of CYP19A1 protein in the obesity group was higher than that in the control group after TSH stimulation (P = 0.014, P < 0.001, and P = 0.004, respectively). With the increase of TSH concentrations, the expression of CYP19A1 mRNA and protein in the two groups significantly increased (all P < 0.001). Early puberty and elevated serum aromatase and TSH levels were found in obese female mice. In the granulosa cells of obese mice, TSH directly regulates aromatase expression in a dose-dependent manner.

Phenylbutyrate Treatment in a Boy with MCT8 Deficiency: Improvement of Thyroid Function Tests and Possible Livertoxicity.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare X-chromosomal inherited disease leading to severe cognitive impairment, muscular hypotonia and symptoms of peripheral thyrotoxicosis. Experimental approaches aiming to functionally rescue mutant MCT8 activity by the chemical chaperone phenylbutyrate (PB) demonstrated promising effects in vitro for several MCT8 missense mutations. The objective was to evaluate biochemical and clinical effects of PB in doses equivalent to those approved for the treatment of urea cycle disorders in a boy with MCT8 deficiency due to a novel MCT8 missense mutation c.703G > T (p.V235L). During a treatment period of 13 months, PB led to a significant decrease of elevated TSH and T3 serum concentrations, while fT4 increased. Weight z-score of the toddler remained remarkably stable during the treatment period. Neurodevelopmental assessments (BSID-III) revealed a slight increase of gross motor skills from developmental age 4 to 6 months. However, increasing liver enzyme serum activities and accumulation of phenylacetate (PAA) in urine led to treatment interruptions and dose alterations. In vitro analyses in MDCK1 cells confirmed the pathogenicity of MCT8 p.V235L. However, while PB increased expression of the mutant protein, it did not rescue T3 transport, suggesting a PB effect on thyroid function tests independent of restoring MCT8 activity. In a clinical attempt of PB treatment in MCT8 deficiency we observed a significant improvement of thyroid hormone function tests, tendencies towards body weight stabilization and slight neurodevelopmental improvement. Hepatotoxicity of PB may be a limiting factor in MCT8 deficiency and requires further investigation.

52 Alleviating antinutritional effects of high soybean meal diets for nursery pigs through multienzyme and acidifier supplementation

Abstract This study evaluated the effect of multienzyme and acidifier supplementation in high soybean meal (SBM) diets on performance and allergenic response in nursery pigs. A total of 240 weaned pigs, 5.9 ± 0.8 kg body weight (BW), were allotted to 5 dietary treatments with 8 replicates in a randomized complete block design. Dietary treatments were low SBM diet (17% in phase 1 and 20% in phase 2), standard SBM diet (22% in phase 1 and 25% in phase 2), high SBM diet (30% in phase 1 and 35% in phase 2), high SBM diet with multienzyme supplementation (100 ppm of phytase, 500 ppm of carbohydrase, 250 ppm of protease, and 25 ppm of keratinase), and high SBM diet with multienzyme and acidifier (0.5%) supplementation. The enzyme combination was selected based on an in-vitro digestion experiment evaluating the degradation rate for antinutritional factors present in SBM. Diets were provided in a 3-phase feeding program: phase 1 (wk 1), phase 2 (wk 2 and 3), and phase 3 (wk 4 to 6); common corn-SBM based diet. Growth performance was measured at the end of each phase along with blood collection for serum IGF-1, IgA, and IgE analyses. One pig per pen was euthanized to collect intestinal tissue for histomorphology and ileal digesta for sIgA analysis. Data were analyzed using MIXED procedure of SAS and fecal score data was analyzed using FREQ procedure of SAS. Pigs fed high SBM diets with multienzyme or with multienzyme and acidifier tended to have a greater (P = 0.08) average daily gain compared with pigs fed High-SBM diet during phase 2 by 12.5%. Pigs fed high SBM diets with multienzyme and acidifier supplementation had greater (P &amp;lt; 0.05) average daily feed intake compared with pigs fed high SBM diet in phase 2. During phase 1 and 2, pigs fed high SBM diets supplemented with multienzyme or multienzyme plus acidifier had less incidence of soft and watery feces (χ2 &amp;lt; 0.05) than those fed high SBM diet. Dietary treatment did not affect serum concentrations of T4, IGF-1, IgA, and IgE. Pigs fed high SBM diet with multienzyme and acidifier supplementation had less (P &amp;lt; 0.05) concentration of sIgA in the ileal digesta on d 14 compared with high SBM diet (24.2 vs 33.8 mg/mL) but similar to low SBM diet (22.7 mg/mL). Pigs fed high SBM diet with multienzyme and acidifier supplementation had greater (P &amp;lt; 0.05) jejunal villus height to crypt depth ratio on d 7 compared with low SBM by 12%. In conclusion, supplementation with multienzyme or multienzyme and acidifier in high SBM diets could reduce the negative impact of high SBM inclusion in nursery pig diets by improving growth performance, promoting intestinal health, and reducing allergenic response in nursery pigs.

138 Growth performance and physiological response of nursery pigs fed a high canola meal diet with acidifiers

Abstract This study investigated the impact of feed additives aimed at reducing gut pH on the growth performance and physiological responses of nursery pigs when fed a high canola meal (CM) diet. A total of 315 nursery pigs, 6.0 ± 1.2 kg body weight (BW), were allotted to one of five dietary treatments with 9 replicates (7 pigs/pen) in a randomized complete block design. Dietary treatments were PC: corn-soybean meal-based diet with 20% CM, NC: corn-soybean meal-based diet with 40% CM; NC+A: NC diet with acidifier at 1,500 ppm, NC+B: NC diet with encapsulated butyrate at 500 ppm, and NC+A+B: NC diet with acidifier and encapsulated butyrate. All diets were formulated to meet or exceed the nutrient requirements of NRC (2012). All pigs received a common Phase 1 nursery diet during week 1 following weaning. Experimental diets were provided in Phase 2 (wk 2 and 3) and Phase 3 (wk 4 to 6). Individual pig BW and pen feed consumption were measured for each phase to calculate growth performance. At the conclusion of each phase, blood samples were collected from one pig per pen for analysis of serum triiodothyronine (T3) and thyroxine (T4) concentrations. The selected pig was euthanized within 24 h, and its organ weights and pH of digesta were measured. The results were analyzed using MIXED procedure in SAS with the pen as an experimental unit. There was no difference in BW and average daily gain throughout the overall period. However, PC treatment exhibited greater (P &amp;lt; 0.05) average daily feed intake in phase 3 by 18.2% and overall period by 13.4% compared with NC treatment and no difference with NC+A+B treatment. The NC+A and NC+A+B treatments tended to improve (P ≤ 0.10) gain to feed ratio in phase 3 by 17.9% and overall period by 16.1% compared with PC treatment, respectively. At the end of phase 3, the PC treatment tended (P &amp;lt; 0.10) to have greater serum T4 concentrations compared with NC and NC+A treatments (3.2 vs 2.5 and 2.4 ug/dL, respectively), whereas there was no difference between PC and NC+A+B treatments. In phase 3, the thyroid gland weight for PC treatment was less (P &amp;lt; 0.05) than for NC treatment (0.156 vs 0.202 g/kg), whereas there was no difference among PC, NC+B, and NC+A+B treatments. In phase 3, dietary encapsulated butyrate decreased (P &amp;lt; 0.05) the pH of jejunal digesta compared with PC treatment (6.28 vs 7.01), and dietary encapsulated butyrate treatments (NC+B and NC+A+B) tended to decrease (P &amp;lt; 0.10) the pH of hind-colonic digesta compared with the pH of PC treatment by 6.2% and 7.2%. In conclusion, dietary encapsulated butyrate in combination with acidifier may alleviate thyroid dysfunction that is anti-nutritional effect of high canola meal diets.

Low thyroxine serves as an upstream regulator of ecophysiological adaptations in Ansell's mole-rats.

About 10% of all rodent species have evolved a subterranean way of life, although life in subterranean burrows is associated with harsh environmental conditions that would be lethal to most animals living above ground. Two key adaptations for survival in subterranean habitats are low resting metabolic rate (RMR) and core body temperature (Tb). However, the upstream regulation of these traits was unknown thus far. Previously, we have reported exceptionally low concentrations of the thyroid hormone (TH) thyroxine (T4), and peculiarities in TH regulating mechanisms in two African mole-rat species, the naked mole-rat and the Ansell's mole-rat. In the present study, we treated Ansell's mole-rats with T4 for four weeks and analyzed treatment effects on the tissue and whole organism level with focus on metabolism and thermoregulation. We found RMR to be upregulated by T4 treatment but not to the extent that was expected based on serum T4 concentrations. Our data point towards an extraordinary capability of Ansell's mole-rats to effectively downregulate TH signaling at tissue level despite very high serum TH concentrations, which most likely explains the observed effects on RMR. On the other hand, body weight was decreased in T4-treated animals and Tb was upregulated by T4 treatment. Moreover, we found indications of the hypothalamus-pituitary-adrenal axis potentially influencing the treatment effects. Taken together, we provide the first experimental evidence that the low serum T4 concentrations of Ansell's mole-rats serve as an upstream regulator of low RMR and Tb. Thus, our study contributes to a better understanding of the ecophysiological evolution of the subterranean lifestyle in African mole-rats.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

Exploring Thermoregulatory Responses and Hormonal Changes in Heat Stressed Assam Hill Goats

Background: Livestock productivity and health are adversely affected by heat stress (HS). The aim of this study was to determine the effects of HS on the thermoregulation and hormonal profile in Assam Hill Goats reared in the subtropical hilly regions of Meghalaya so as to arrive at a conclusion on its heat adaptation abilities. Methods: An experiment was conducted during the year 2022 for 120 days with twelve (12) Assam Hill Goats, aged between 3-5 months, randomly divided into 2 groups (n=6 per group). The goats in group I were exposed to HS through natural exposure to sunlight during the extreme summer months (May to August) for 07 hours (8 AM to 3 PM) during grazing. The control animals (CON, group II) were maintained under shade with no exposure to sunlight. Thermoregulatory responses viz., rectal temperature, respiratory rate and pulse rate and body weight data were recorded every 15 days interval of the sampling period. The hormonal profile viz., serum T3 (nmol/L), T4 (nmol/L) and Cortisol (ng/mL) were also determined. Result: Results revealed a significant (p less than 0.05) increase in rectal temperature, pulse rate (day 45 onwards to day 120) and respiratory rate in HS group in comparison to CON. A significantly (p less than 0.05) lower average daily gain was recorded in HS group. Serum T3 and T4 concentrations were significantly (p less than 0.05) reduced and cortisol concentration was significantly (p less than 0.05) elevated in HS group in comparison to CON. In conclusion, Assam Hill Goats exposed to environmental HS shows elevated thermoregulatory responses, decreased thyroid hormone activity and increased cortisol activity to reduce production to support life sustaining activities in the hilly regions.

Association between maternal hypothyroidism, baby birth weight, and adult cardiovascular disease risk: insights from ECG measurements.

Thyroid hormone (TH) deficiency during pregnancy may affect cardiovascular function in offspring rats. This study aimed to evaluate the effect of TH deficiency during gestation, on the electrocardiogram indices of young and middle-aged offspring of male rats. Eight female rats were equally divided into hypothyroid and control groups. The hypothyroid mothers received 0.025% 6-propyl-2-thiouracil (PTU) in drinking water throughout pregnancy, while control mothers consumed only tap water. Following birth, male rats from each group were observed for 4 months (young age) and 12 months (middle-aged). The group known as fetal hypothyroid (FH) consisted of rats born from hypothyroid mothers. The serum T4 and TSH concentrations from mothers and newborn male rats were assayed at the end of gestation. Lead II electrocardiogram (ECG) was recorded for 5 minutes using Power Lab, AD Instruments. There was a significant rise in the P wave voltage in young FH rats, whereas, it was decreased in middle-aged control and FH rats. The voltage of QRS decreased and its duration increased in the young and middle-aged FH rats compared to the corresponding control groups. Duration and voltage of the T wave were significantly altered in the young and middle-aged FH groups. PR and QT intervals significantly increased in the young and middle-aged FH groups compared to their controls. Maternal hypothyroidism affected the electrocardiogram indices of offspring rats, possibly signaling cardiovascular problems later in life.

Relationship between thyroid function and sex hormones in female German shepherd dogs.

Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited. Estrous stage may influence thyroid function in German Shepherd dogs. Longitudinal, observational, non-randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17-β-estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period. Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism. Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17-β-estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17-β-estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy. Different stages of estrus can influence the measurement of TT4 in female dogs.

Influence of silver nanoparticles on mRNA expression of thyroid hormone-related genes in the thyroid gland and liver of laying hens

The widespread use of silver nanoparticles (AgNPs) in consumer products and animal husbandry raises the need to study their impact on living organisms. This study was conducted on Hy-Line Brown hens at the age of 25 weeks with an average weight of 1.58 kg. Hens for 2 weeks received a solution of 50 nm AgNPs at a concentration of 100 pm (experimental group; n = 6) or a solution in which the nanoparticles were suspended (control group; n = 6). Thyroid hormones (thyroxine – T4, triiodothyronine – T3) were evaluated in the blood plasma and expression profiles of genes involved in thyroid hormone (TH) synthesis (TSHR, NIS, TPO, TG), metabolism (DIO1, DIO2, DIO3) and transport (MCT8, MCT10, LAT1) were determined in the chicken thyroid gland. Furthermore, iodothyronine deiodinase, TH transporter and TH receptor (THRA, THRB) mRNA expressions were evaluated in the livers isolated from the same chickens. AgNPs did not affect serum T4 levels but elevated serum T3 concentration. The results showed that AgNPs increased DIO3 mRNA in the thyroid gland. In turn, in the liver AgNPs administration significantly upregulated DIO2 and downregulated MCT10 mRNA levels. These results indicate that exposure to AgNPs leads to a tissue-specific alternative expression of genes engaged in TH metabolism. Moreover, the mRNA expression of DIO2 in the liver showed a positive correlation with plasma T3 levels. In conclusion, AgNPs may have an impact on TH metabolism by affecting deiodinases and TH transporter MCT10 mRNA expression.

Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review.

The SCL16A2 gene encodes the thyroid hormone (TH) transporter MCT8. Pathogenic variants result in a reduced TH uptake into the CNS despite high serum T3 concentrations. Patients suffer from severe neurodevelopmental delay and require multidisciplinary care. Since a first compassionate use study in 2008, the development of therapies has recently gained momentum. Treatment strategies range from symptom-based approaches, supplementation with TH or TH-analogs, to gene therapy. All these studies have mainly used surrogate endpoints and clinical outcomes. However, the EMA and FDA strongly encourage researchers to involve patients and their advocacy groups in the design of clinical trials. This should strengthen the patients' perspective and identify clinical endpoints that are clinically relevant to their daily life. We involved patient families to define patient-relevant outcomes for MCT8 deficiency. In close collaboration with patient families, we designed a questionnaire asking for their five most preferred therapeutic goals, which, if achieved at least, make a difference in their lives. In addition, we performed a systematic review according to Cochrane recommendations of the published treatment trials. We obtained results from 15 families with completed questionnaires from 14 mothers and 8 fathers. Improvement in development, especially in gross motor skills, was most important to the parents. 59% wished for head control and 50% for sitting ability. Another 36% wished for weight gain, 32% for improvement of expressive language skills, and 18% for a reduction of dystonia/spasticity, less dysphagia, and reflux. Paraclinical aspects were least important (5-9%). In a treatment trial (n=46) and compassionate use cases (n=83), the results were mainly inconclusive, partly due to a lack of predefined patient-centered clinical endpoints. We recommend that future trials should define a relevant improvement in "development" and/or other patient-relevant outcomes compared to natural history as treatment goals.

An optimized radioimmunoassay for quantification of total serum thyroxine (T4) in fetal, neonatal, and pregnant rats

Identifying xenobiotics that interrupt the thyroid axis has significant public health implications, given that thyroid hormones are required for brain development. As such, some developmental and reproductive toxicology (DART) studies now require or recommend serum total thyroxine (T4) measurements in pregnant, lactating, and developing rats. However, serum T4 concentrations are normally low in the fetus and pup which makes quantification difficult. These challenges can be circumvented by technologies like mass spectrometry, but these approaches are expensive and not always widely available. To demonstrate the feasibility of measuring T4 using a commercially available assay, we examine technical replicates of rat serum samples measured both by liquid chromatography mass spectrometry (LC/MS/MS) and radioimmunoassay (RIA). These samples were obtained from rats on gestational day 20 (dams and fetuses) or postnatal day 5 (pups), following maternal exposure to the goitrogen propylthiouracil (0–3 ppm) to incrementally decrease T4. We show that with assay modification, it is possible to measure serum T4 using low sample volumes (25–50 μL) by an RIA, including in the GD20 fetus exposed to propylthiouracil. This proof-of-concept study demonstrates the technical feasibility of measuring serum T4 in DART studies.

A-059 Evaluation of Free Thyroxin Levels in Patients with Low Thyroxin Binding Globulin Concentrations: Is There Interference in the FT4 Indirect Method?

Abstract Background Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in serum. Variations in the serum concentration of TBG determine proportional variations in the total serum concentrations of T4 and T3, without implying changes in function, as long as the free fraction remains normal. Several common clinical conditions lead to significant alterations in TBG levels, the most important factor behind low levels being genetic defects. As TBG is encoded by a gene located on the X chromosome, the defects are more easily manifested in males. Differences in FT4 concentrations were observed in sera from subjects with TBG abnormalities, when FT4 are measured by different immunoassays, specially at extremes of TBG concentrations. The objective of this study was to evaluate FT4 levels by indirect method in patients with low TBG concentrations. Methods We analyzed blood samples requesting serum TBG, TSH and FT4 levels from patients admitted to a private reference clinical laboratory in Brazil, from January 01, 2017 to December 31, 2022. Anonymized data on laboratory tests was available from a database of the local Laboratory Information System. All the patients included had TSH within the reference range, 0.4–4.3 mUI/mL (ECLIA, Modular, Roche). FT4 was measured by ECLIA (0.7–1.8 ng/dL) and TBG by ICMA, Immulite, Siemens, 13–39 mcg/mL. Results 357 patients with low TBG levels were evaluated, 220 (62%) men, 137 (38%) women; mean age 35 yrs (19 d to 88 yrs). They were divided in six groups according TBG levels (mcg/mL): &amp;lt;3.5–17 (M 15, F2); 3.5 to 6.0 - 26 (M 20, F 6); 6.1 to 8.0 - 30 (M 25, F 5); 8.1 to 9.9 - 59 ( M 32, F 27); 10.0 to 11.9 - 139 (M 78, F 61); 12.0 to 12.9 - 86 (M 50, F 36). Three patients had FT4 levels above 1.8 (1.85; 1.87 and 1.96) ng/mL, all them male, with TBG levels &amp;lt;3.5; 5.79 and 9.53 ng/mL, respectively. Conclusion FT4 Indirect methods are developed taking into account the presence, in the serum, of a thyroxine binding capacity within the normal range, a fact that does not occur in individuals with extreme TBG deficiency. In this study, we found only one slightly elevated FT4 value among 17 patients with TBG values below 3.5 mcg/mL, suggesting little interference of very low TBG levels in this indirect free T4 method.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial

BackgroundUnderstanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients.MethodsRadioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 μg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 − 24 were calculated at the last visit.ResultsSerum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 − 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group.ConclusionCombined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested.IRCT registration numberIRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13. Registration date: 08/12/2021.

Integrated Proteomics and Metabolomics Analyses of Serum in Chinese Patients with Severe and Active Graves' Orbitopathy: A Cross-sectional Study.

The present study aims to investigate the alterations of serum proteomic and metabolomic profiles in Chinese patients with severe and active Graves' Orbitopathy (GO). Thirty patients with GO and 30 healthy volunteers were enrolled. The serum concentrations of FT3, FT4, T3, T4, and thyroid-stimulating hormone (TSH) were analyzed, after which TMT labeling-based proteomics and untargeted metabolomics were performed. Metabo- Analyst and Ingenuity Pathway Analysis (IPA) was used for integrated network analysis. A nomogram was established based on the model to explore the disease prediction ability of the identified feature metabolites. One hundred thirteen proteins (19 up-regulated and 94 down-regulated) and 75 metabolites (20 increased and 55 decreased) were significantly altered in GO compared to the control group. By combining the lasso regression, IPA network, and protein-metabolite-disease sub-networks, we extracted feature proteins (CPS1, GP1BA, and COL6A1) and feature metabolites (glycine, glycerol 3-phosphate, and estrone sulfate). The logistic regression analysis revealed that the full model with the prediction factors and three identified feature metabolites had better prediction performance for GO compared to the baseline model. The ROC curve also indicated better prediction performance (AUC = 0.933 vs. 0.789). A new biomarker cluster combined with three blood metabolites with high statistical power can be used to discriminate patients with GO. These findings provide further insights into the pathogenesis, diagnosis, and potential therapeutic targets for this disease.

The efficacy of iodinated ethyl esters of safflower seed oil (Carthamus tinctorius L.) in the control of iodine deficiency in sheep

Iodine is an essential component of the thyroid gland hormones (T3 and T4), necessary for mammalian life. Iodine deficiency leads to inadequate thyroid hormone production, and all the consequences of iodine deficiency stem from the associated hypothyroidism. Iodized oil is made by treating a fatty vegetable oil with iodine or hydriodic acid and is an effective long-term means of iodine supplementation. The type and fatty acids profile in the parent oil, as well as the way iodine is trapped, affect the physicochemical properties and effectiveness of the product. This research was conducted to study the effect of iodinated safflower oil on preventing iodine deficiency disorders (IDD) in livestock, compared with a commercial iodine supplement. Iodinated fatty acid ethyl esters prepared from safflower seed oil (IFAEESSO). Thirty Farahani ewes with a history of iodine deficiency were divided into three groups, including control and two treatment groups. The treatment groups received 390 mg of iodine by an intramuscular injection of 1.26 ml of IFAEESSO (n = 10) or 1.5 ml of Depodine® (n = 10), respectively. Serum iodine, thyrotropin stimulating hormone (TSH), T3 and T4 concentrations were assayed at baseline and every 30-day intervals over six months period. Iodine supplementation resulted in a significant increase in serum inorganic iodine over five months with Depodine and IFAEESSO (P < 0.01). Serum T3 and T4 concentrations also increased in treatment groups (P < 0.01), while the concentration of TSH didn’t change. The mean T4 and T3 concentrations were 3.16 μg /dl and 53.89 ng /dl in the control group, which increased to 3.50 μg /dl and 58.88 ng/dl for Depodine and 3.88 μg /dl and 63.55 ng/dl for IFAEESSO, respectively. The serum inorganic iodine and thyroid hormone concentrations were significantly higher in the IFAEESSO group than in the Depodine group (P < 0.01). IFAEESSO is an effective supplement against IDD and more efficient than that of Depodine to increase serum iodine concentration, and thyroid hormone production.

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA &gt;250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. while under normal long term CHOW feeding the SNS component may be as little as 3 % of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

Thyroid evaluation in suspicious hypothyroid adult dogs before and after treatment.

The purpose of this study was to measure circulating TSH, T4 and fT4 concentrations in dogs submitted to a clinical visit for general symptoms (weight gain, polyuria and polydipsia, changes in hair coat). Twenty-eight dogs, 14 cross-breed and 14 purebreds (Golden Retriever, Labrador, Doberman), of both sexes (14 males and 14 females), aged 8 to 14 years, were assessed. No significant differences of circulating TSH, T4 , fT4 concentrations between the baseline and after therapeutic treatment nor between intact and neutered females were observed. Compared to baseline values, intact males showed higher TSH concentrations (p⟨0.01), and castrated males lower TSH concentrations (p⟨0.01) after therapeutic treatment. Compared to intact males, castrated males showed baseline TSH concentrations higher (p⟨0.01), but lower (p⟨0.01) after therapeutic treatment. No significant differences of T4 and fT4 concentrations between baseline conditions and after therapeutic treatment, nor between intact and castrated males, were observed. The experimental sample considered in this study falls within that casuistry involving elevated TSH concentrations but low serum T4 and fT4 concentrations or close to the minimum physiological cut-off, in which the common clinical signs suggestive of hypothyroidism was, essentially, overweight and neglected appearance of the hair.

Rat Serum Osteocalcin Concentration Is Decreased by Restriction of Energy Intake

We studied the effects of energy restriction on serum osteocalcin concentration and bone formation rate in rats. The experiment was designed to achieve energy restriction by reducing the carbohydrate intake while providing identical quantities of protein, fat, vitamins and minerals. Energy intakes of three groups of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum calclum, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Energy restriction (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin concentrations, although the serum concentrations of its key regulators, i.e., 1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4 were significantly lower in the energy-restricted groups. However, our results do not support their implication in the regulation of serum osteocalcin synthesis by energy intake. Serum osteocalcin concentration was positively correlated with bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P < 0.05) rates suggesting that its decrease resulted from a reduction of bone formation, and not from abnormal mineralization, because osteoid seam thickness was not modified. Energy intake seems to be an important determinant of serum osteocalcin concentration and bone formation; however, the exact mechanism underlying this regulation remains to be determined.