Plasma Thyroid-stimulating Hormone Levels Research Articles

Causal association of TSH with ischemic heart diseases and heart failure: A 2-sample Mendelian randomization study.

Thyroid dysfunction is associated with the risk of cardiovascular disease; however, whether plasma thyroid-stimulating hormone (TSH) levels in subjects with euthyroidism affect the risk of cardiovascular disease remains unclear. This study aimed to investigate the causal association between plasma TSH levels and cardiovascular diseases, particularly ischemic heart disease and heart failure (HF). Summary statistics from the Integrative Epidemiology Unit Open genome-wide association studies Project and FinnGen consortium were used to investigate the causal relationship between plasma TSH levels and the risk of cardiovascular diseases. Two-sample Mendelian randomization analysis using inverse-variance weighting as the primary method was performed. The MR Pleiotropy RESidual Sum and Outlier and leave-one-out methods were used to ensure the robustness of our findings. Genetically determined plasma TSH levels were associated with major coronary heart disease events (OR 1.0557, 95% CI 1.0141-1.0991), all-cause HF (OR 0.9587, 95% CI 0.9231-0.9956), and HF + non-ischemic cardiomyopathy (OR 0.9318, 95% CI 0.8786-0.9882). After the Bonferroni correction, the causation described above disappeared. In the secondary analysis, genetically determined higher TSH levels were associated with a higher risk for unstable angina pectoris (OR 1.0913, 95% CI 1.0350-1.1507), but were associated with a lower risk for HF + overweight (OR 0.9265, 95% CI 0.8821-0.9731). These results were further validated using sensitivity analysis. Our findings show that increased plasma TSH levels in patients with euthyroidism may increase the risk of unstable angina pectoris but reduce the risk of HF in overweight patients. This evidence indicates that plasma TSH levels may need to be carefully controlled in specific patients.

SAT498 A Challenging Case of Hypothyroidism Requiring Frequent Primary Care Visits to Achieve Euthyroidism

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: We report a patient with persistent primary hypothyroidism despite multiple adjustments in thyroid medication. Clinical Case: A 67-year-old white man with multinodular goiter underwent total thyroidectomy in 2016 for abnormal thyroid nodule biopsy. Surgical pathology revealed papillary thyroid cancer with lymph node metastasis. He subsequently received radioactive iodine ablation treatment. His plasma thyroid stimulating hormone (TSH) level was noted to be 0.275 uIU/mL (normal range 0.35-4.00 uIU/mL) in January 2017 on levothyroxine 224 micrograms daily. Subsequently, his plasma TSH level continued to remain elevated with variable levels despite multiple titrations of his levothyroxine dosage, counseling, and multiple follow-up visits. Plasma TSH level went up as high as 108.140 uIU/mL (normal range changed to 0.55-4.78 uIU/mL). In January 2022, plasma TSH level normalized to 3.125 uIU/mL with high plasma free thyroxine level of 2.45 ng/dL (normal range 0.89-1.76 ng/dL), but plasma TSH level increased again to 5.190 uIU/mL in April 2022. Home care nurse was involved in monitoring of the patient taking thyroid medication daily and correctly but was unsuccessful. The patient and his son reported taking thyroid medicine daily and correctly. There was no concern for malabsorption or interference with any of his medications. The patient was subsequently asked to come to primary care clinic every week for six weeks with all his medications. He was unable to come to endocrinology clinic due to travel time being more than one hour. His repeat plasma TSH normalized to 1.010 uIU/mL. The etiology of previously high plasma TSH level was suspected due to non-compliance with taking his thyroid medication. Non-compliance was discussed in detail with the patient and his son, including life-threatening consequences of hypothyroidism. The patient verbalized understanding and was willing to comply with the recommendations. The patient was then asked to stop coming weekly to primary care clinic. Repeat plasma TSH level in October 2022 was again noted to be high at 80.723 uIU/mL. He again claimed compliance, but weekly visits to primary care clinic were resumed. In December 2022, he was noted to have low plasma TSH level of 0.232 uIU/mL. Conclusion: Once weekly visits seem impractical but might be required in a certain group of patients with persistent abnormal thyroid hormone levels where no etiology can be found. Presentation Date: Saturday, June 17, 2023

Higher Levels of Plasma Fetuin-A, Nrf2, and Cytokeratin 18 in Patients with Hashimoto's Disease.

Fetuin-A is a protein that exhibits proatherogenic, pro-inflammatory, and anti-inflammatory effects with increased insulin resistance and adipocyte dysfunction. The nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that is crucial for protecting cells against oxidative damage. As a cell death product, cytokeratin 18 (CK18) levels increase during necrosis and apoptosis of both normal and tumor cells. We analyzed the plasma levels of three biomarkers based on the hypothesis that they might be related to some pathophysiological pathways in Hashimoto's disease. We compared 34 female patients with overt hypothyroidism due to Hashimoto's disease (Group 1) with 34 age-matched healthy females (Group 2). For comparison, plasma levels of thyroid-stimulating hormone (TSH), fetuin-A, Nrf2, and CK18 were measured in all participants. In group 1, the mean TSH levels (31.4±15.3) were significantly higher than those in group 2 (2.6±1.0) (p<0.001). The levels of mean fetuin-A (606.7±34.2) and Nrf2 (1.3±0.6) were found to be significantly higher in group 1 than in group 2 (440.0±34.2 vs. 0.7±0.2) (p<0.001 for both). CK18 levels in group 1 (0.36±0.13) were also significantly higher than in group 2 (0.26±0.16) (p=0.020). A significant correlation was observed between TSH levels and fetuin-A (r=0.401, p=0.001). Increased levels of fetuin-A, Nrf2, and CK18 may be a consequence or cause of the pathophysiological pathways of Hashimoto's disease. The clinical significance of increased levels of these biomarkers requires further investigation.

Association between Thyroid Function and Ocular Parameters.

During development, thyroid hormones play an important role in eye development, while in adults, some pathological thyroid conditions can affect the normal functioning of the eyes. Thyroid eye disease is the most well-known eye pathology caused by a pathological thyroid condition. Few studies have investigated the association between ocular parameters and thyroid function. Thus, in this study, we aimed to examine whether thyroid activity affects ocular parameters. This cross-sectional study included 4633 healthy adults recruited within the 10,001 Dalmatians project of the Croatian Biobank. The plasma levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb) were measured by an immunoassay. We determined 20 ocular parameters for each participant (10 for each eye, including corneal radius, corneal thickness, anterior chamber depth, anterior chamber angle, lens thickness, posterior chamber length, axial length, intraocular lens power (IOL), spherical power, and cylinder power). Patients with hyperthyroidism had thicker corneas compared to euthyroid individuals. Corneal thickness was also negatively associated with plasma TSH levels. Intra-ocular lens power was higher in patients with clinical hypothyroidism, while spherical power was higher in euthyroid individuals with positive antibodies compared to euthyroid individuals. Intra-ocular lens power negatively correlated with fT4 levels, while spherical power positively correlated with TgAb, TPOAb, and Tg levels and negatively correlated with TSH levels. The anterior chamber angle was positively associated with plasma TSH levels and TPOAb levels and negatively associated with plasma fT4 levels. These findings suggest an interesting interplay between ophthalmic measures and thyroid status, detectable even in the general adult population.

The effect of exposure on cattle thyroid after the Fukushima Daiichi nuclear power plant accident

Nuclear plant accidents can be a risk for thyroid cancer due to iodine radioisotopes. Near the Fukushima Daiichi nuclear power plant, cattle were exposed to radiation after the accident occurred in May 2011. Here we estimated the total radiation exposure to cattle thyroid and its effects on thyroid function. Until October 2016, the estimated external exposure dose in Farm A was 1416 mGy, while internal exposure dose of 131I, 134Cs, and 137Cs were 85, 8.8, and 9.7 mGy in Farm A and 34, 0.2, and 0.3 mGy in Farm B, respectively. The exposed cattle had thyroid with relatively lower weight and lower level of stable iodine, which did not exhibit any pathological findings. Compared with the control, the plasma level of thyroid-stimulating hormone (TSH) was higher in Farm A cattle born before the accident, while the plasma thyroxine (T4) was higher in Farm A cattle born after the accident, suggesting that exposed cattle showed slight hyperactivation of the thyroid gland. In addition, Farm A cattle have higher level of cortisol, one of the anterior pituitary gland-derived hormones. However, we did not observe a causal relationship between the radiation exposure and cattle thyroid.

Relationship between the development of hyperlipidemia in hypothyroidism patients.

As shown in the previous studies, hypothyroidism (HT) is identified to be closely associated with the elevated plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and with the decreased plasma levels of high density lipoprotein cholesterol (HDL-C). On the other hand, the thyroid hormone (TH), which has been considered as a vital hormone produced and released by the thyroid gland, are well-established to regulate the metabolism of plasma TC; whereas other evidence proposed that the thyroid-stimulating hormone (TSH) also regulated the plasma cholesterol metabolism independently of the TH, which further promotes the progression of hyperlipidemia. Nevertheless, the potential mechanism is still not illustrated. It is worth noting that several studies has found that the progression of HT-induced hyperlipidemia might be associated with the down-regulated plasma levels of TH and the up-regulated plasma levels of TSH, revealing that HT could promote hyperlipidemia and its related cardio-metabolic disorders. Otherwise, multiple novel identified plasma proteins, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), have also been demonstrated to embrace a vital function in modulating the progression of hyperlipidemia induced by HT. In the present comprehensive review, the recent findings which elucidated the association of HT and the progression of hyperlipidemia were summarized. Furthermore, other results which illustrated the underlying mechanisms by which HT facilitates the progression of hyperlipidemia and its cardio-metabolic disorders are also listed in the current review.

Levothyroxine Administration during Ramadan: A Prospective Randomized Controlled Trial

Background and Aim: We have previously shown in a retrospective analysis that the plasma thyroid-stimulating hormone (TSH) rises significantly post-Ramadan in levothyroxine-treated hypothyroid patients, possibly as a result of lifestyle alterations and time restrictions during the nonfasting period from dusk until dawn. The aim of this study is to determine the best time to instruct patients to take levothyroxine during Ramadan so as to minimize changes in thyroid function tests during this period. Methods: In a randomized prospective design, hypothyroid patients taking levothyroxine were randomized to receive instructions to take levothyroxine at one of the following 3 times during Ramadan: (group 1) at dusk 30-min before Iftar meal, (group 2) 3 or more hours after Iftar meal, or (group 3) at dawn 30-min before Suhur meal. Thyroid function tests were performed within 3 months before Ramadan and within 6 weeks post-Ramadan. Data from patients with at least 1 blood test before or after Ramadan were analyzed using mixed-effects regression models. Results: Plasma TSH levels were available at one or more time points for 148 patients, group 1 (n = 50), group 2 (n = 46), and group 3 (n = 52). A statistically significant within-patient increase in plasma TSH was seen in patients at the 25th percentile pre-Ramadan in groups 2 and 3 (p values <0.001), but not in group 1. A statistically significant within-patient decrease in plasma TSH was found in patients at the 75th percentile in group 1 only. For patients at the 50th percentile pre-Ramadan, no statically significant within-patient changes were found, though descriptively, increases in plasma TSH were observed for groups 2 and 3, while a decrease was observed in group 1. Conclusions: Our data suggest that instructing patients to take levothyroxine at the time of breaking the fast 30 min before the Iftar meal minimizes unfavorable changes in plasma TSH post-Ramadan. In contrast, instructing patients to take levothyroxine 3 h post-Iftar or 30 min before Suhur led to a greater rise in post-Ramadan TSH.

Thyroid function, brain bioelectrical activity and heart rate variability in patients with hypertension

Aim. To study the levels of thyroid-stimulating hormone (TSH) and thyroid hormones (TH), frequency and amplitude parameters of alpha wave, parameters of heart rate variability, hemodynamics and their relationship in patients with hypertension (HTN) and healthy individuals.Material and methods. We studied 75 patients with stage 2 HTN and 70 healthy individuals. All patients underwent an electroencephalography, 24-hour blood pressure monitoring. Weighted average heart rate variability was calculated. We determined blood plasma levels of TSH and TH. Statistical processing, multiple regression and correlation analysis were carried out using the Statistica v. 10.0.1 software package (StatSoft Inc).Results. In patients with HTN, TSH and TH were lower than in the control group by 50% and 38%, respectively. The а-index was also 40% lower. Patients with HTN were characterized by lower amplitude, frequency and power of а-wave, and weighted average heart rate variability by 35%, 13-35%, and 30%, respectively. Pulse wave velocity in patients with HTN exceeded the control group by 18%, and the systemic dynamic response was 2,2 times higher. The groups differed in the characteristics of the relationship of а-wave between the brain lobes and hemispheres with TSH, TH, heart rate variability and hemodynamics.Conclusion. The concentration of TSH and TH is interrelated with the frequency and amplitude parameters of alpha wave, heart rate variability and hemodynamic parameters in hypertensive patients.

Interplay between Thyroid Hormones and Stearoyl-CoA Desaturase 1 in the Regulation of Lipid Metabolism in the Heart.

Stearoyl-CoA desaturase 1 (SCD1), an enzyme that is involved in the biosynthesis of monounsaturated fatty acids, induces the reprogramming of cardiomyocyte metabolism. Thyroid hormones (THs) activate both lipolysis and lipogenesis. Many genes that are involved in lipid metabolism, including Scd1, are regulated by THs. The present study used SCD1 knockout (SCD1−/−) mice to test the hypothesis that THs are important factors that mediate the anti-steatotic effect of SCD1 downregulation in the heart. SCD1 deficiency decreased plasma levels of thyroid-stimulating hormone and thyroxine and the expression of genes that regulate intracellular TH levels (i.e., Slc16a2 and Dio1-3) in cardiomyocytes. Both hypothyroidism and SCD1 deficiency affected genomic and non-genomic TH pathways in the heart. SCD1 deficiency is known to protect mice from genetic- or diet-induced obesity and decrease lipid content in the heart. Interestingly, hypothyroidism increased body adiposity and triglyceride and diacylglycerol levels in the heart in SCD1−/− mice. The accumulation of triglycerides in cardiomyocytes in SCD1−/− hypothyroid mice was caused by the activation of lipogenesis, which likely exceeded the upregulation of lipolysis and fatty acid oxidation. Lipid accumulation was also observed in the heart in wildtype hypothyroid mice compared with wildtype control mice, but this process was related to a reduction of triglyceride lipolysis and fatty acid oxidation. We also found that simultaneous SCD1 and deiodinase inhibition increased triglyceride content in HL-1 cardiomyocytes, and this process was related to the downregulation of lipolysis. Altogether, the present results suggest that THs are an important part of the mechanism of SCD1 in cardiac lipid utilization and may be involved in the upregulation of energetic metabolism that is associated with SCD1 deficiency.

Greater effects of high- compared with moderate-intensity interval training on thyroid hormones in overweight/obese adolescent girls.

To investigate the effects of 12-week high-intensity- (HIIT) vs. moderate-intensity-interval training (MIIT) on thyroid stimulating hormone (TSH) and thyroxine (T4) and insulin-resistance in overweight/obese adolescent girls. Twenty four adolescent girls (age 16.5±1.36yrs) were randomly allocated into three groups: (1) HIIT (2 blocks per session of 6-8 bouts of 30s runs at 100-110% maximal aerobic speed (MAS), with 30s active recovery between bouts at 50% MAS; n=8), (2) MIIT (2 blocks per session of 6-8 bouts of 30s runs at 70-80% MAS, with 30s active recovery between bouts at 50% MAS; n=8) and (3) control group (no exercise, n=8). Each training groups engaged in three sessions per week during three months. Anthropometric parameters, aerobic capacity, homeostasis model assessment index for insulin resistance (HOMA-IR) as well as plasma TSH and T4 levels were assessed in all subjects before- and after-training. Following both training programs, body mass, body mass index Z-score, waist circumference and body fat decreased, while aerobic capacity increased. However, TSH and T4 concentrations decreased only after the HIIT (-30.47%, p<0.05, ES=1.42 and-12.86%, p<0.05, ES=1.18; respectively). The HOMA-IR decreased in both training groups (-26.25%, p<0.05, ES=1.87 for MIIT and-21.72%, p<0.05, ES=2.14 for HIIT). Twelve weeks of HIIT was effective in reducing circulating TSH and T4 levels, unlike MIIT, in overweight/obese adolescent girls. These findings indicated that the stimulation of pituitary-thyroid function is more sensitive to training intensity than training duration. Further studies are needed to confirm this conclusion.

Radiation-Induced Hypothyroidism in Patients with Oropharyngeal Cancer Treated with IMRT: Independent and External Validation of Five Normal Tissue Complication Probability Models.

Simple SummaryHypothyroidism is a common complication of therapeutic irradiation in the neck area. Several dose-response models have been proposed to predict its’ occurrence based on clinical and radiomic features. We aimed to externally validate the results of five such models in a prospectively recruited cohort of 108 patients with oropharyngeal cancer. Two of the evaluated models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance. Both models are based on mean thyroid dose and thyroid volume. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse. Short-term change in the level of thyroid-stimulating hormone (TSH) after radiation therapy was not indicative of hypothyroidism development in long term. We conclude that the models by Rønjom et al. and by Boomsma et al. are feasible for long-term prediction of hypothyroidism in oropharyngeal cancer survivors treated with intensity-modulated radiation therapy.We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03–1.19) for mean thyroid dose and 0.87 (95%CI 0.81–0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79–0.93) and 0.84 (95%CI: 0.76–0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65–1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

A Biochemichal and Ultrastructural Study on the Effect of Toluene on the Pars Distalis of Anterior Pituitary Glands of Adult Male Albino Rats

Background: Toluene is an environmental chemical pollutant and widely used as organic solvent and in production of many industrial products. It has systemic toxic effects on many organs as liver, kidney and the central nervous system and cause immune dysfunction. It can affect nerve myelination and cross the blood-brain barrier. Little is known about the exact effect of toluene exposure on the cells of anterior pituitary and no adequate studies were found about the effect of toluene on the morphological and histological structure of the pituitary cells.Aim: To assess the ultra structural of the pars distalis after toluene exposure. And to correlate any biochemical changes with the histological alteration as a trial to know the possible mechanism behind these changes.Materials and Methods: 20 adult male albino rats were divided into control group consisted of 10 rats and toluene exposed group 10 rats were exposed once a day to vapors of toluene (1000 ppm) for 15 minutes for 45 days. Blood samples were taken from the heart chambers of for assessment of the thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), adrencorticotrophic hormone (ACTH), growth hormone (GH) and prolactin. The anterior lobes of pituitary glands were immediately dissected out. Each specimen was separated into two parts; one processed and stained with hematoxylin & eosin and the other part was examined by electron microscope.Results: Biochemical: in the toluene-exposed group there was significant reduction in plasma level of GH, TSH, FSH and LH hormones and non-significant reduction in ACTH prolactin.Microscopic: the exposed group cells show complete loss of normal architecture in many areas and had vacuolated cytoplasm, shrunken asymmetrical nucleus with more thickened chromatin and few secretory granules.Conclusion: The toluene exposure induced morphological changes in most of cells of pars distalis and their secreted hormones

T189. FREE THYROXIN CONCENTRATIONS MODERATE THE RESPONSE TO A COGNITIVE REMEDIATION THERAPY IN PEOPLE WITH EARLY PSYCHOSIS: PRELIMINARY FINDINGS

BackgroundCognitive deficits are a common cause of functional disability in people with psychotic disorders. Cognitive remediation produces moderate improvements in cognitive performance in people with schizophrenia, although there is variability in the responses between patients. As previous longitudinal studies suggest that free thyroxin (FT4) levels influence attention cognitive tasks in patients with early psychosis, we aimed to conduct a pilot study to explore whether thyroid hormones might predict the response to cognitive remediation therapy (CRT) in patients with first-episode psychosis.Methods27 patients (8 women; 19 men) with first-episode psychosis aged between 18 and 35 years old were randomized to receive a computerized CRT for three months (2 sessions/week) (N=14) or treatment as usual (TAU) (N=13). A full cognitive battery (CANTAB Schizophrenia) was administered at baseline and follow-up (3 months later, after the CRT/TAU period). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Data were analyzed on an intention-to-treat basis. Correlation analyses were conducted to explore the association between TSH and FT4 levels and cognitive changes over time. An ANOVA for repeated measures was used to compare longitudinal changes over time by the experimental group while adjusting for TSH and FT4 levels. Significance was defined as p<0.05.ResultsTSH concentrations were not associated with cognitive changes over time. FT4 concentrations were associated with cognitive worsening over time in cognitive tasks dealing with reaction time (simple median movement time [r= 0.60, p= 0.003]; simple median reaction time [r= 0.44, p= 0.039]), sustained attention (signal detection for the rapid visual processing task [r= -0.46, p= 0.028]) and verbal memory (immediate recognition [r= -0.54, p= 0.008]; delayed recognition [r= -0.48, p= 0.019]). The ANOVA for repeated measures did not show time by group effects although a time by FT4 significant effect was found for cognitive tasks dealing with these cognitive domains (p<0.05 for all).DiscussionAlthough a direct effect of the CRT on cognitive improvement was not found, baseline FT4 concentrations appeared to predict the response to CRT in people with early psychosis. Significant associations were found for cognitive domains dealing with attention processes, which are in accordance with previous studies exploring the association between thyroid function and cognitive functioning in early psychotic patients. Our preliminary findings suggest that the determination of thyroid function status might be important for establishing which patients could show cognitive improvements over time. If these results are replicated in larger studies, the determination of thyroid status might help identify those individuals more prone for showing cognitive improvements, and allowing the implementation of a personalized medicine approach in the field of cognitive rehabilitation in psychosis.

Sub-chronic exposure to Kalach 360 SL, Glyphosate-based Herbicide, induced bone rarefaction in female Wistar rats

We investigated the effects of Kalach 360 SL (KL), Glyphosate (G)-based herbicide, on bone tissue in different groups of female Wistar rats. Group 1 (n = 6) received a standard diet and served as a control, groups 2 and 3 (n = 6 each) received 0.07 ml (D1: 126 mg/Kg) and 0.175 ml (D2: 315 mg/Kg) of KL dissolved in the water for 60 days. The plasma was used to examine the metabolic balance markers (calcium, phosphorus, phosphatase alkaline (PAL), and vitamin D (vit D) and hormonal status (oestrogen and thyroid hormones). As a result, sub-chronic exposure to KL induced a perturbation of bone metabolism (calcium and phosphorus) and hormonal status disturbance. The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Moreover, the KL disrupting eff ;ect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in female rats breast-fed from rats treated with D and D2 of KL. This eff ;ect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). Thus, that KL leads to hypothyroidism. Decrease in levels of oestrogen and thyroid dysfunction led to a disruption in the skeletal bone. The histological study and SEM in bone results allowed us to observe, in rats exposed to KL, the thinning and discontinuity of bone trabecular with a significant decrease in the number of nodes (intertrabecular links).In conclusion, KL sub-chronic exposure caused an aspect of osteoporosis.

Assessment of Thyroid Profile of Type 1 and Type 2 Diabetes Mellitus Patients and Patients with Diabetic Complications

This study was undertaken to assess the thyroid profile of diabetes mellitus (DM) patients and patients with some associated complications in the Edo state, Nigeria. Blood samples from 267 subjects, consisting of 164 diabetic patients (24 type 1 DM and 140 type 2 DM) and 103 nondiabetic apparently healthy individuals (as controls), were analyzed. The thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels were determined using the enzyme linked immunosorbent assay (ELISA). From the result obtained, the T3 level was found significantly (p &lt; 0.05) higher in diabetic-nephropathy (D-NEPHR) patients than the control subjects, while the TSH and T4 levels of D-NEPHR were insignificantly (p &gt; 0.05) higher than those of the control group. The mean TSH level was significantly (p &lt; 0.05) lower in diabetic hypertensive patients when compared with the control group, while the plasma T3 level was significantly (p &lt; 0.05) higher in diabetic hypertensive patients when compared with the control group. There was no significant difference (p &gt; 0.05) in the mean value of T4 of diabetic hypertensive patients when compared with the control subjects. The mean plasma T3 and T4 were significantly (p &lt; 0.05) higher in diabetic neuropathy (D-NEUR) patients than those of control subjects. There were no significant (p &gt; 0.05) differences in the mean plasma TSH level of D-NEUR patients when compared with those of control subjects. The mean plasma T3and T4 levels of diabetic patients with coronary heart disease (DM-CHD) were significantly (p &lt; 0.05) higher than those of control subjects while the mean plasma TSH level of DM-CHD was significantly (p &lt; 0.05) lower than that of control subjects. No significant (p &gt; 0.05) difference in the mean plasma TSH, T4, and T3 levels of diabetic retinopathy subjects when compared with those of control subjects was obtained.

Subclinical Hypothyroidism and Lipid Metabolism: To Treat or Not to Treat?

Abstract Thyroid hormones have multiple complex effects on lipid synthesis and metabolism. These physiological actions are well documented in overt hypothyroidism where the elevated levels of total cholesterol, low density lipoporotein cholesterol and possibly triglycerides are reverted by levo-thyroxine therapy. Subclinical hypothyroidism, defined as elevated serum thyroid stimulating hormone in the presence of reference range of free thyroxine and free triiodothyronine concentrations, is a relatively frequent clinical conditions. Many clinical and epidemiological studies have evaluated lipid metabolism, markers of subclinical atherosclerosis and other cardiovascular risk factors in subclinical hypothyroidism as well as the need of replacement therapy in these patients. The available results are rather conflicting, with variable and inconclusive results. Moreover, no consensus still exists on the clinical significance and treatment of this mild form of thyroid failure. On the contrary, available evidences suggest that patients with plasma thyroid stimulating hormone levels above 10 mU/L should be treated with levo-thyroxine, since may have an increased risk of cardiovascular disease. However, the epidemiological evidences suggest being rather conservative in older people, since higher thyroid stimulating hormone is associated with lower risk of multiple adverse events in this population. In this review, we summarized the current evidences on the association between subclinical hypothyroidism and lipid metabolism and the effect of levo-thyroxine therapy on lipid parameters.

Thyroid-stimulating hormone (TSH) is associated with 30-day mortality in hip fracture patients.

The aim of this study is to assess the possible association between thyroid-stimulating hormone (TSH) and mortality in hip fracture patients. The study is based on a hip fracture database from Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all hip fracture patients (ICD-10 codes DS720 (femoral neck), DS721 (pertrochanteric), and DS722 (subtrochanteric)) admitted to Bispebjerg Hospital from 1996 to 2012. From this database, we identified all surgically treated hip fracture patients aged > 60years with available plasma TSH-measurements at admission. Of the 914 included patients (24% men and 76% women), 10.5% died within 30days. At inclusion, 161 (17.6%) of the patients were hyperthyroid (TSH < 0.65mIU/L), 58 (6.4%) were hypothyroid (TSH > 4.8mIU/L), while 695 (76.0%) were euthyroid (0.65 < TSH < 4.80mIU/L), p = 0.03. Mortality was significantly higher in the two higher quartiles of TSH [Q3 (13.0%) and Q4 (15.4%)] compared to the two lower quartiles [Q1 (7.4%) and Q2 (6.2%), p = 0.0003. After adjustment for age, sex and Charlson Comorbidity Index (CCI) in a Cox proportional hazard model, the risk of 30-day mortality continued to be increased in patients with TSH above the median as compared to patients with TSH below the median (HR 2.1 (1.4-3.3), p = 0.0006]. The study demonstrates increased 30-day mortality in surgically treated hip fracture patients with plasma TSH levels above the median (1.41mIU/L) at admission, even after adjusting for age, sex and CCI.

Normal-range thyroid-stimulating hormone levels and cardiovascular events and mortality in type 2 diabetes

AimsThyroid dysfunction is a risk factor for cardiovascular disease. Whether thyroid function within the normal range is a risk factor for cardiovascular disease remains uncertain. The aim of this study is to evaluate whether plasma thyroid-stimulating hormone (TSH) levels in the normal range are a risk factor for cardiovascular disease and mortality in participants with type 2 diabetes mellitus with high cardiovascular risk. MethodsWe included 1265 participants with high cardiovascular risk, type 2 diabetes, and TSH within the normal range (0.35–5.00 mIU/L) from the Second Manifestations of ARTerial disease cohort. The primary outcome was major cardiovascular events (MACE; vascular death, stroke and myocardial infarction). Secondary outcomes of interest were the separate vascular outcomes and all-cause mortality. Cox proportional hazard models were used to evaluate the risk of plasma TSH levels on all outcomes. ResultsA total of 191 MACE occurred during a total follow-up of 8183 years. Plasma TSH levels were not associated with MACE (hazard ratio (HR) per mIU/L TSH increase 0.93; 95% confidence interval (95%CI) 0.80–1.08). With a total of 54 strokes during the study period, plasma TSH was associated with a lower risk of stroke (HR per mIU/L 0.64, 95% CI 0.45–0.89). There was no association between plasma TSH levels and risk of myocardial infarction, vascular death, or all-cause mortality. ConclusionsHigher TSH levels within the normal range are associated with a lower risk of stroke in high-risk patients with type 2 diabetes, but not associated with the risk of other cardiovascular events or mortality.

Slc:Wistar/ST rats develop unilateral thyroid dysgenesis: A novel animal model of thyroid hemiagenesis

Developmental anomalies of the thyroid gland lead to congenital malformations such as thyroglossal duct cysts and thyroid dysgenesis. However, the pathogenesis of thyroid dysgenesis remains unclear due to the lack of suitable animal models. This study demonstrated that Slc:Wistar/ST rats frequently developed unilateral thyroid dysgenesis, including hemiagenesis, characterized by the absence of one lobe. In Wistar/ST rats, each thyroid lobe was frequently different in size, and approximately 27% and 20% of the rats presented with hemihypoplasia and hemiagenesis of the thyroid gland, respectively. Dysgenesis was predominant on the left side in both sexes, without sex differences. At a young age, thyroid hemiagenesis did not alter body weight. In rats of both sexes with thyroid hemiagenesis, plasma total triiodothyronine and total triiodothyronine levels remained unchanged while plasma thyroid-stimulating hormone levels were significantly elevated in young rats. The remaining thyroid lobes increased in weight, but the follicular epithelial cells appeared normal in terms of their height and proliferating activities. On the side of thyroid dysgenesis, the parathyroid glands were normally localized and were situated at the same location as the contralateral glands. The ultimobranchial body remnants were localized at the level of the thyroid gland along with the cranial thyroid artery and vein, forming cell clusters or cystic structures and containing calcitonin-positive C-cells. In conclusion, Wistar/ST rats developed unilateral thyroid dysgenesis and may be novel and useful animal models for thyroid hemiagenesis in humans and for morphogenesis of pharyngeal pouch-derived organs.

Genome-wide meta-analysis identifies novel loci associated with free triiodothyronine and thyroid-stimulating hormone.

Thyroid hormones are essential for the normal function of almost all human tissues, and have critical roles in metabolism, differentiation and growth. Free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels are under strong genetic influence; however, most of the heritability is yet unexplained. In order to identify novel loci associated with fT3, fT4 and TSH serum levels we performed a genome-wide meta-analysis of 7411206 polymorphisms in up to 1731 euthyroid individuals from three Croatian cohorts from Dalmatia region: two genetically isolated island populations and one mainland population. Additionally, we also performed a bivariate analysis of fT3 and fT4 levels. The EPHB2 gene variant rs67142165 reached genome-wide significance for association with fT3 plasma levels (P = 9.27 × 10-9) and its significance was confirmed in bivariate analysis (P = 9.72 × 10-9). We also found a genome-wide significant association for variant rs13037502 upstream of the PTPN1 gene and TSH plasma levels (P = 1.67 × 10-8). We identified a first genome-wide significant variant associated with fT3 plasma levels, as well as a novel locus associated with TSH plasma levels. These findings are biologically relevant and enrich our knowledge about the genetic basis of pituitary-thyroid axis function.