Low Thyroid-stimulating Hormone Research Articles

Description of a patient with Graves’ disease post COVID-19 with negative serology

We are presenting a 62-year-old African-American female who was admitted to our Emergency Department (ED) with septic shock due to pneumonia and diverticulitis. After improvement of the admitting conditions, we found out that the patient developed 1-month post-COVID-19 pneumonia Graves’ disease. The diagnosis was challenging because the patient was negative for thyroid-stimulating immunoglobulin (TSI) and thyroid receptor antibodies (TRAb). The clinical picture was highly suggestive of GD. The patient complained of increased sweating, palpitation, lower extremities weakness, and lack of sleep before the septic shock and after the COVID-19 infection. We palpated a trill and we heard a bruit on her thyroid gland which was a specific finding for the hypervascular gland as in GD. Our physical findings were confirmed by the laboratory findings of thyrotoxicosis with increased free thyroxin levels (Ft4) and very low thyroid stimulating hormone (TSH). The Doppler flow ultrasound of the thyroid confirmed bilateral hypervascular thyroid gland suggestive of hyperthyroidism without nodules. The patient did not have any thyroid disease or complaints before her COVID-19 infection. This is as far as we know the first described patient post-COVID-19 induced GD without TSI and TRAb.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Thyroid Function Impact on Cardiac Structure, Function and Disease Risk: Evidence of Causal Associations in European Ancestry

BackgroundThyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality. ObjectiveTo investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their impact on cardiac structure and function assessed by cardiac magnetic resonance imaging. MethodsA comprehensive two-sample Mendelian randomization (MR) analysis was conducted, utilizing summary data from large-scale meta-analyses of European ancestry individuals. ResultsGenetically determined lower TSH levels (OR 0.928, 95% CI: 0.884 to 0.974, P = 0.003) and genetic risk of hyperthyroidism (OR 1.049, 95% CI: 1.016 to 1.083, P = 0.003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable MR revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function. ConclusionsOur study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias.

Pituitary Hyperplasia and Overt Hypothyroidism Induced by Methimazole in an Adolescent Girl with Resistance to Thyroid Hormone Accompanying Hashimoto’s Thyroiditis: A Case Report

We describe a 13-year-old girl who presented at her local hospital with a diffuse goiter and had discrepant thyroid function test (TFT) of elevated free T4 (FT4), free T3 (FT3) levels with mildly elevated thyroid-stimulating hormone (TSH) and a pituitary magnetic resonance imaging (MRI) report of a pituitary hyperplasia. She was referred to our hospital where a repeat TFT found low FT4 and high TSH levels, and high levels of antithyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies, leading to the diagnosis of Hashimoto’s thyroiditis (HT) with overt primary hypothyroidism. The girl had a good response after daily 100 µg levothyroxine treatment for 8 months with decreased goiter size along with disappearance of the pituitary mass. However, her FT4 and FT3 levels were elevated while the TSH was in the high normal range, although at this time there were no signs of hyperthyroidism. A genetic study confirmed our provisional diagnosis that the patient had a p.Pro453Thr monoallelic loss-of-function mutation of the thyroid hormone receptor beta (THRB) gene, suggesting the diagnosis of coexisting resistance to thyroid hormone-β (RTHβ) and HT in this patient.

Cadmium Exposure was Associated with Sex-Specific Thyroid Dysfunction: Consistent Evidence from Two Independent Cross-Sectional Studies Based on Urinary and Blood Cadmium Measurements.

Population-based studies on the association between cadmium (Cd) exposure and thyroid function are limited and have shown conflicting results. Two independent cross-sectional studies using different Cd biomarkers were carried out in six rural areas with different soil Cd levels in China. Thyroid dysfunction was defined based on levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4). Multivariable linear regression, multiple logistic regression, and restrictive cubic splines models were used to estimate the association between Cd and thyroid dysfunction. For both of the two independent studies, higher Cd levels were observed to be associated with lower TSH levels and higher risk of thyroid dysfunction. The negative relationship between urinary Cd and TSH was found in both total participants (β = - 0.072, p = 0.008) and males (β = - 0.119, p = 0.020) but not in females; however, the negative relationship between blood Cd and TSH was only found in females (β = - 0.104, p = 0.024). Higher urinary Cd was associated with higher risk of thyroid dysfunction (OR = 1.77, p = 0.031), while higher blood Cd was associated with higher risk of thyroid dysfunction (OR = 1.95, p = 0.011). Results from the two independent cross-sectional studies consistently suggested that higher Cd levels were associated with sex-specific thyroid dysfunction.

A Cross-Sectional Study of Acute Coronary Syndrome and Thyroid Profile: Dissecting the Relationship to Improve Patient Care.

Thyroid-releasing hormones are pivotal in regulating cardiovascular (CVS) function and maintaining its hemodynamics and homeostasis. Even a minor alteration in thyroid function has an enormous implication on CVS morbidity and mortality. Moreover, hypothyroidism was found to be a potential menace for coronary artery disease (CAD).The objective of this study was to determine the role of thyroid-releasing hormones in patients suffering from acute coronary syndrome (ACS). Among a cohort of 100 patients suffering with ACS, a complete history and clinical information followed by physical examinationand electrocardiography were recorded. Blood samples were also collected to record the blood sugar levels i.e., fasting blood sugar (FBS), postprandial blood sugar (PPBS), and thyroid profile, including free thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and reverse triiodothyronine (rT3). The data was analyzed using SPSS version 26 software (IBM Corp., Armonk, NY, USA). The study identified alterations in the thyroid hormone levelsin 27% of patients suffering from ACS. The prevalence of euthyroid sick syndrome was found to be 59.3%, while subclinical hypothyroidism and subclinical hyperthyroidism were reported among 18.5% and 14.8% of patientsrespectively. Therewas no significant difference found between males and females. The study illustrated a greater occurrence of aberrant thyroid hormone profiles among those aged 40-60 years. The ST-elevated myocardial infarction (STEMI) group had a statistically significant higher prevalence of an aberrant thyroid hormone profile compared to the non-ST-elevated myocardial infarction (NSTEMI) and unstable angina (UA)groups (p=0.02). A total of nine patients died with ACS and all of those had statistically significant low fT3 and TSH values while higher rT3 values (p<0.05). An atypical thyroid status has been found to elevate the likelihood of developing CAD and experiencing CVS mortality. This condition can impact ventricular function and serum cholesterol levelsas well as heart rate and rhythm. Therefore, understanding this relationship could potentially lead to improved treatment strategies for individuals with ACS which will further prevent major CVS complications.

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

A high level of thyroid-stimulating hormone is a risk factor for the development of chronic kidney disease in men: a 10-year cohort study.

Hypothyroidism has been reported to be associated with chronic kidney disease (CKD). However, the impact of thyroid-stimulating hormone (TSH) on new onset of CKD and its gender dependence remain undetermined. We investigated the association of serum TSH level and the development of CKD defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or positive for urine protein in 28,990 Japanese subjects who received annual health examinations. After excluding subjects with no data for serum TSH, urinalysis and eGFR and those with CKD at baseline, a total of 10,392 subjects (men/women: 6802/3590, mean age: 48 years) were recruited. During a 10-year follow-up, 1185 men (6.7%) and 578 women (2.9%) newly developed CKD. Multivariable Cox proportional hazard models after adjustment of age, body mass index, smoking habit, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease and eGFR (≥ 90 mL/min/1.73 m2) showed that the hazard ratio (HR) for the development of CKD in the high TSH (> 4.2 mU/L) group was significantly higher than that in the low TSH (≤ 4.2 mU/L) group in men (HR [95% confidence interval]: 1.41 [1.09-1.83]) but not in women (1.08 [0.77-1.51]). There was a significant interaction between sex and the category of TSH level for the development of CKD (p = 0.02). The adjusted HR with a restricted cubic spline increased with a higher level of TSH in men but not in women. In conclusion, a high level of TSH is associated with an increased risk for the development of CKD in men but not in women.

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.

Hypothyroxinemia and weight velocity in preterm infants.

Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA. Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children's Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity. In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA. We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Elevation of free triiodothyronine (fT3) levels by Plasmodium falciparum independent of thyroid stimulating hormone (TSH) in children with uncomplicated malaria.

Malaria parasites have a devastating effect on the infected host. However, there is a paucity of data on the effect of Plasmodium falciparum on thyroid hormones. This case-control study (1:1) involved children <16 years of age with uncomplicated malaria. Hematological parameters were determined using the URIT-5380 hematology analyzer (China). Later, levels of thyroid hormones, namely free triiodothyronine (fT3), free tetraiodothyronine (fT4), and thyroid-stimulating hormone (TSH), were determined using human ELISA kits (DiaSino ELISA kit, Zhengzhou, China). Ninety children with malaria and ninety matched control group were studied. Overall, compared to the control group, lower TSH (3.43 ± 1.25 vs. 3.84 ± 1.34, p = 0.035) and elevated levels of fT3 levels (5.85 ± 1.79 vs. 3.89 ± 1.19, p < 0.001) were observed in patients with malaria. However, fT4 levels were comparable between cases and control group (16.37 ± 2.81 vs 17.06 ± 3.5, p = 0.150). Free T3 levels were significantly higher in children <10 years (p < 0.001) and higher among male children with malaria (p < 0.001). Overall, there was a significant positive relationship between parasite counts and fT3 (R = 0.95, p < 0.001). Furthermore, body temperature was positively correlated with fT3 (R = 0.97, p < 0.001). Isolated fT3 thyrotoxicosis was observed in falciparum malaria, especially in children <10 years and male malaria patients, independent of TSH. This observation could explain the severity of malaria in children.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones

Background/ObjectivesPregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. MethodsIllinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8–40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. ResultsIn women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with −5.65% (95% CI: −9.79, −1.28) lower testosterone and −0.09 μIU/mL (95% CI: −0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: −0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with −1.77% (95% CI: −4.08, 0.58) lower TT4 and −0.18 μIU/mL (95% CI: −0.33, −0.03) lower TSH. We also identified select chemical interactions. ConclusionSome biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

Thyroid hormone may predict treatment failure in Kawasaki disease.

In systemic inflammatory conditions, inflammatory cytokines can cause low thyroid hormone levels. There are no reports discussing the relation between thyroid hormone levels and response to treatment for Kawasaki disease. We investigated 67 patients who underwent treatment in the acute phase of Kawasaki disease. We divided patients into two groups based on their response to initial intravenous immunoglobulin (IVIG) treatment: the responder group (n = 40), and the non-responder group (n = 27). The serum levels of the thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were compared before and after treatment in all patients, and between responder and non-responder groups. The FT3, FT4, and TSH levels were low before the initial treatment and increased significantly after treatment (p < 0.05). The FT3, FT4, and TSH levels before treatment were significantly lower in the non-responder group than in the responder group (p < 0.05). Logistic regression analysis suggested that the addition of pre-treatment FT4 values to Gunma score was useful in predicting treatment failure. Thyroid hormone and TSH levels were lower in the non-responder group than in the responder group in the initial IVIG treatment for Kawasaki disease. This study suggests that Kawasaki disease in the acute phase is associated with low thyroid hormone levels and TSH. It is possible that these hormone levels predict response to the initial IVIG.

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta-analysis.

Thyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta-analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD. We searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD. A total of 13 studies were included in the analysis. Compared to non-PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD=-0.59, 95%CI=-1.04 to -.15, p=.009; FT3: SMD=-0.40, 95%CI=-.51 to -.30, p=.000) and higher serum FT4 levels (SMD=0.33, 95%CI=.07-.59, p=.013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4. Our results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

Clinical features of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis: a new aspect of paraneoplastic autoimmune condition.

The pathogenesis of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis postimmune checkpoint inhibitor therapy. All 9 patients exhibited extremely low growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels; 2 had a slightly atrophic pituitary gland; 4 had thymoma, and 5 had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in 5 cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis.

Thyroid Hormone Status in Severely Malnourished Children between 6 Months to 5 Years Admitted to Nutritional Rehabilitation Centre of a Tertiary Care Hospital

Introduction: Severe malnutrition poses a significant risk to the thyroid gland's function and hormonal balance, which can lead to numerous physiological and developmental complications. Understanding the relationship between severe malnutrition and thyroid hormone status is crucial for the effective management of these children.&#x0D; Aim and Objective: To investigate the prevalence and patterns of thyroid hormone abnormalities in severely malnourished patients with subgroup analysis in Marasmus, Kwashiorkor, and edematous malnourished patients.&#x0D; Methodology: We conducted a cross-sectional study involving 116 children diagnosed with severe acute malnutrition (SAM). The study protocol was approved by the Institution Ethics Committee. Well-informed written consent in the local language was taken from parents. SAM was diagnosed and managed according to WHO criteria (1). Comprehensive laboratory investigations were conducted to assess serum levels of thyroid-stimulating hormone (TSH), free thyroxine (T4), and triiodothyronine (T3). Statistical analysis was performed to examine the associations between these variables and SAM.&#x0D; Results: Most of the 116 subjects included in the study were male (53.4%) and had a lower socioeconomic status (43.9%). The age distribution of the children aged below 5 years revealed that 46.5% were between 12 and 36 months old. In the present study, Marasmus was 55.2%, Kwashiorkor was 12.1%, and edematous malnutrition was 32.7%. Among 116 participants, 94.8% were discharged, while 5.2% were expired during treatment. The mean levels of fT3, fT4, and TSH were 1.88±1.06 pg/ml, 0.99±0.84 ng/dl, and 3.22±0.87 µIU/ml, respectively. Most SAM patients had low fT3, fT4, and TSH levels relative to the normal range.&#x0D; Conclusion: Monitoring of thyroid hormone status in SAM patients is mandatory for this vulnerable population.

Relationship between Iron Deficiency and Thyroid Function: A Systematic Review and Meta-Analysis.

Objective: Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. Methods: This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "iron deficiency", "thyroid function", "thyroid disease", "thyroid dysfunction", and "hypothyroidism". A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran's Q testing and heterogeneity indices (I2) were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Results: Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: -0.24 mIU/L; 95% CI -0.41, -0.07; I2 = 100%, p = 0.005), FT4 (MD: -1.18 pmol/L; 95% CI -1.43, -0.94; I2 = 99%, p < 0.000001), and FT3 (MD: -0.22 pmol/L; 95% CI -0.32, -0.12; I2 = 99%, p < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Conclusion: Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.

Are We Missing Hypothyroidism among Children with Sickle Cell Anaemia?

Children with sickle cell anaemia have been reported to have potential risk of hypothyroidism from chronic blood transfusions and probable thyroid tissue ischaemia. However, few studies on hypothyroidism status of children with sickle cell anaemia in Nigeria are available. The objective of this study was to determine the prevalence of hypothyroidism among children with sickle cell anaemia. A cross sectional study that assayed the thyroid hormones and thyroid stimulating hormone (TSH) of 71 children with sickle cell anaemia was conducted at Olabisi Onabanjo University Teaching Hospital Sagamu. Using age appropriate hormonal reference values, the subjects were classified into subclinical, primary and secondary hypothyroidism. The mean serum TSH, Free T3, and Free T4 were comparable irrespective of age category (p > 0.05). No subject was identified to have low TSH value while 7.0% had high TSH value. Low free T3 was identified in 1.4% and 8.5% had high free T3 values. Low free T3 and free T4 were seen in 11.3% each of the subjects. The overall prevalence of primary, secondary and subclinical hypothyroidism was 0%, 0% and 4.2%, respectively. Sub-clinical hypothyroidism does occur in Nigerian children with sickle cell anaemia. Routine screening for hypothyroidism is advocated in all children with sickle cell anaemia.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer

BackgroundOf the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium–iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. MethodsWe immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, β+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high–thyroid-stimulating hormone receptor and low–thyroid-stimulating hormone receptor–expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor–positive THJ529T tumors. ResultsImmunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor–positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor–expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. ConclusionOur observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor–positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.