Subclinical Hypothyroidism Research Articles

Congenital central hypoventilation syndrome in korea: 20 years of clinical observation and evaluation of the ventilation strategy in a single center

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children’s Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001). Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS.What is Known:• Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system.• The disease-defining gene of CCHS isPHOX2Bgene – most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 – 20/33).What is New:• We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype.• National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.

The Effect of Apalutamide on Thyroid Function in Prostate Cancer Patients.

Apalutamide (APT) is a nonsteroidal antiandrogen medication used to treat metastatic castrate-sensitive and nonmetastatic castrate-resistant prostate cancer. Early clinical trials of APT identified thyroid dysfunction as a common adverse effect of therapy, but the clinical presentation and management of APT-induced hypothyroidism has not been studied. The objective of our study is to elucidate the clinical presentation and treatment approach of APT-associated thyroid dysfunction in prostate cancer patients. We report a case series of 16 patients with APT-associated thyroid dysfunction during prostate cancer treatment at 2 academic medical centers. Patient clinical parameters, thyroid function laboratory data, and thyroid hormone requirements over the course of APT treatment were analyzed. Among the 16 patients in our case series with APT-associated hypothyroidism, 3 had no prior thyroid disease and 13 had preexisting hypothyroidism. The patterns of thyroid dysfunction included overt and subclinical hypothyroidism. The median time from APT initiation to thyroid function test abnormality was 19 weeks, but occurred in some cases as early as 2 to 4 weeks. Hypothyroidism was effectively managed with thyroid hormone replacement using levothyroxine (LT4), though some patients with preexisting hypothyroidism required a 2- to 3-fold dose increase while on APT to achieve a euthyroid state. In the subset of patients who completed or stopped APT therapy, thyrotropin levels fell at a median of 11 weeks post APT therapy and thyroid hormone requirements decreased to near pre-APT levels. APT-associated thyroid dysfunction presents as new or worsening hypothyroidism and should prompt initiation or increase in thyroid hormone replacement. Monitoring of thyroid function tests is recommended every 1 to 2 months for all patients on APT and 2 to 3 months after completion of APT.

#1246 The impact of severe nephrotic syndrome on thyroid function

Abstract Background and Aims Nephrotic syndrome (NS) is a clinical condition characterized by massive urinary loss of proteins, mostly albumin, but also hormones and their carrier proteins among others. The most frequently reported hormonal complication is thyroid dysfunction. The study aimed to assess the frequency of thyroid dysfunction in NS and its association with carrier protein levels and indicators of disease severity. Method A case-control study was conducted involving patients with newly diagnosed or relapsed severe NS, defined as proteinuria &amp;gt; 3.5 g/day and serum albumin ≤ 2.5 g/dL (NS group), and patients without proteinuria (control group). The evaluation included thyroid hormone profiles, serum levels of carrier proteins (prealbumin – PAB, and thyroid-binding globulin – TBG), and markers reflecting the course of NS. Results Forty-two nephrotic and 40 matched non-proteinuric patients were enrolled. The NS group comprised 67% males with a mean age of 49 years and an average proteinuria of 8.9 g/day (Table 1). The leading cause of NS was minimal change disease (22 patients), followed by membranous nephropathy (11 patients). The other causes included: amyloidosis (3 patients: AL – 2 cases, A – 1 case), focal segmental glomerulosclerosis (2 patients) and lupus nephritis (1 case). In 5 cases, no histological diagnosis was made. Thyroid dysfunction secondary to NS was observed in the majority of patients, occurring 18-times more frequently than in the control group (67% vs 10%, OR = 18, 95% CI: 5.3-60.7). Euthyroid sick syndrome was the most commonly seen in NS (15 cases, 36%), followed by overt (8 cases, 19%) and subclinical hypothyroidism (5 cases, 12%). According to the current guidelines, levothyroxine supplementation was required in 11 patients (26% of the NS group, 36% of those with thyroid dysfunction). Serum TSH correlated inversely with PAB (R = −0.63, p &amp;lt; 0.001), and positively with TBG (R = 0.39, p = 0.010), while no relationships were found between carrier proteins and free hormones (fT3 or fT4). The only indicator of NS severity related to thyroid function was serum albumin. It correlated, however, only with TSH (R = −0.41, p = 0.007), not with free hormones. Additionally, neither histological type, nor clinical course of NS distinguished between euthyroidism, euthyroid sick syndrome, or hypothyroidism (Table 2). Conclusion Thyroid dysfunction is a common complication of severe NS. Although euthyroid sick syndrome predominates, the proportion of patients with hypothyroidism who may potentially require levothyroxine replacement therapy remains substantial.

Association between the triglyceride-glucose index and thyroid disorders: a cross-sectional survey and Mendelian randomization analysis.

Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

#1080 Low-T3 syndrome: “endemic” in hemodialysis patients?

Abstract Background and Aims In hemodialysis patients, low-T3 syndrome is more prevalent than in the general population and was found to be associated with malnutrition and inflammation. Although evidence suggest that low free T3 (fT3) levels predict cardiovascular and all-cause mortality, low-T3 syndrome is usually not treated. The aim of this single-center retrospective observational study was to determine the prevalence of thyroid axis derangements and examine the relationship between thyroid hormones and biochemical and clinical variables in our hemodialysis (HD) patients cohort. Method Patients on thrice-weekly maintenance HD for at least 6 months were enrolled. Patients taking amiodarone, levothyroxine or methimazole were excluded. Data about age, sex, ethnicity, hemodialysis vintage, type of dialysis (bicarbonate dialysis/online hemodiafiltration/acetate-free-biofiltration/hemofiltration with endogenous reinfusion/expanded hemodialysis) were obtained from medical records and values of fT3, fT4, TSH, albumin, LDL, hemoglobin—routinely checked for every patient during hemodialysis sessions—were acquired. Continuous variables are expressed as median and IQR or mean ± SD and categorical variables as absolute value or percentage. The normality of data distribution was tested by Sapiro-Wilk test. Correlations were studied with Pearson and Spearman. T-test and Mann-Whitney U test were performed to compare continuous and categorical variables. Statistical significance was reached with p &amp;lt; 0.05. Results A total of 57 patients on thrice-weekly maintenance HD were enrolled. Most of them were male (70.2%), Caucasians (89.5%), with a mean age of 69 ± 14 years and with a median dialytic vintage of 63 [29; 113] months. Hypertension was the most frequent comorbidity and more than half of the patients was either affected by ischemic, hypertensive or dilatative cardiomyopathy. Most of the patients underwent bicarbonate hemodialysis (42.1%) and overall 57.9% of the study population was treated by convective techniques. Hemoglobin, albumin, LDL cholesterol, fT3 and fT4 values was normally distributed, while those of TSH and PCR were not. A very high prevalence of low-T3 syndrome (75%) was found, 5 patients showed subclinical hypothyroidism and only in a minority of patients thyroid function tests were normal (12%) (Fig. 1). A significant negative correlation between fT3 and age (p = 0.041) and a positive one between TSH and dialytic vintage (p = 0.017) were found (Table 1). In addition, a significant positive correlation between albumin and fT3 was detected, supporting the known association between low T3 and malnutrition. Interestingly, PCR negatively correlated with fT3 and positively with fT4. Patients treated by diffusive techniques showed no statistically significant difference of thyroid hormone levels compared to convective therapies (Table 1). Conclusion Low-T3 syndrome affects the great majority of patients in our hemodialysis population, with a prevalence even higher than that provided by literature. Our investigations confirm that older patients seem to show lower fT3 levels and a longer hemodialysis vintage may correlate with higher TSH levels. The association with inflammation was also confirmed. Considering the known impact on cardiovascular and all-cause mortality already demonstrated, it is important to routinely check thyroid hormones in HD. In addition, further studies should be performed in order to establish the possible impact of the therapeutic correction of this hormonal derangement on hemodialysis patients’ mortality and cardiovascular outcomes.

Subclinical hypothyroidism in Wales from 2000 to 2021: A descriptive cohort study based on electronic health records.

Subclinical hypothyroidism (SCH) is a biochemical thyroid disorder characterised by elevated levels of Thyroid Stimulating Hormone (TSH) together with normal levels of thyroid hormones. Evidence on the benefits of treatment is limited, resulting in persistent controversies relating to its clinical management. This study describes the demographic and clinical characteristics of patients identified as having subclinical hypothyroidism in Wales between 2000 and 2021, the annual cumulative incidence during this period and the testing and treatment patterns associated with this disorder. We used linked electronic health records from SAIL Databank. Eligible patients were identified using a combination of diagnostic codes and Thyroid Function Test results. Descriptive analyses were then performed. 199,520 individuals (63.8% female) were identified as having SCH, 23.6% (n = 47,104) of whom received levothyroxine for treatment over the study period. The median study follow-up time was 5.75 person-years (IQR 2.65-9.65). Annual cumulative incidence was highest in 2012 at 502 cases per 100,000 people. 92.5% (n = 184,484) of the study population had TSH levels between the upper limit of normal and 10mIU/L on their first test. 61.9% (n = 5,071) of patients identified using Read v2 codes were in the treated group. 41.9% (n = 19,716) of treated patients had a history of a single abnormal test result before their first prescription. In Wales, the number of incident cases of SCH has risen unevenly between 2000 and 2021. Most of the study population had mild SCH on their index test, but more than a third of the identified patients received levothyroxine after a single abnormal test result. Patients with clinically recorded diagnoses were more likely to be treated. Given the expectation of steadily increasing patient numbers, more evidence is required to support the clinical management of subclinical hypothyroidism.

MARKERS OF LIPID AND PROTEIN OXIDATION IN THE BLOOD OF WOMEN AND MEN WITH AUTOIMMUNE HASHIMOTO'S THYROIDITIS

Purpose: The aim of this study was to analyze changes in markers of oxidative stress (lipid peroxidation and oxidative modification of proteins) and the total antioxidant activity in the blood of women and men with autoimmune Hashimoto's thyroiditis (HT). Methodology. This study was carried out in a group of 153 individuals. The group of women participating in the study consisted of 109 individuals (71.24%), while the group of men consisted of 44 individuals (28.76%). All persons were divided into two groups: 1) euthyroidism (n = 64; men – n = 18, and women – n = 46); and 2) Hashimoto's autoimmune thyroiditis with subclinical hypothyroidism (n = 89; men – n = 26, and women – n = 63). The functioning of the thyroid gland was additionally verified by measuring the concentration of thyrotropin (TSH), free triiodothyronine (fT3), free tetraiodothyronine (thyroxine, fT4), and antibodies against thyroid peroxidase (anti-TPO). The concentration of thyrotropin, triiodothyronine, free thyroxine and the concentration of antibodies against thyroperoxidase in human serum were determined using the electrochemiluminescence method "ECLIA" on the immunological analyzer Elecsys Cobas e 411 (Hitachi, Japan). In each group of women and men with euthyroidism and Hashimoto's autoimmune thyroiditis with subclinical hypothyroidism, the 2-thiobarbituric acid reactive substances (TBARS), carbonyl derivatives of protein oxidative modification (OMP), and total antioxidant capacity (TAC) were determined. Scientific novelty. Statistically significant changes in levels of oxidative stress markers were not observed. In women with HT, elevated TBARS levels with simultaneously increased TAC levels in the plasma and erythrocytes were observed. Additionally, levels of aldehydic and ketonic derivatives of oxidative modification of proteins in the blood of women with HT were lower compared to the women with the euthyroid state. In men with HT, levels of markers of oxidative stress (except TAC levels in the plasma) were lower compared to those obtained in men with the euthyroid state. Conclusions. Hashimoto's thyroiditis with subclinical hypothyroidism does not have a direct influence on levels of biomarkers of lipid and protein oxidation. The results obtained in the current study highlight the need for future investigations of biomarkers of lipid and protein oxidation, especially depending on the duration of this disease.

THE INFLUENCE OF AGE, PHYSICAL ACTIVITY, SMOKING AND THE PRESENCE OF MYOCARDIAL INFARCTION AND THYROID DISEASES IN THE FAMILY ON THE LEVEL OF ALDEHYDIC AND KETONIC DERIVATIVES OF OXIDATIVE MODIFICATION OF PROTEINS IN THE BLOOD OF WOMEN AND MEN WITH MYOCARDIAL INFARCTS AND HYPOTHYROIDISM

The importance of thyroid hormones in maintaining homeostasis of the cardiovascular system can be inferred from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism and low triiodothyronine syndrome - adversely affect the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidemia, endothelial dysfunction, changes in blood pressure, and the direct effects of thyroid hormones on the myocardium. Purpose: analysis of changes in the concentration of markers of oxidative stress, e.g. oxidation of protein amino acid residues [concentration of aldehydic and ketonic derivatives of oxidatively modified proteins (OMP)] in the blood of individuals with hypothyroidism and/or myocardial infarcts, living in central Pomeranian region, depending on age, physical activity, smoking and the presence of myocardial infarcts and thyroid diseases in the family. Methodology. The level of oxidative stress markers was assessed among 225 individuals, i.e. 132 males (58.67%) and 93 females (41.33%) aged 35-71 years residing in central Pomeranian region. In the obtained blood, an assessment of levels of aldehydic and ketonic derivatives of oxidatively modified protein analyses was carried out. Scientific novelty. According to our research, the level of aldehydic derivatives of oxidative modification of proteins was significantly higher in the elderly (more than 55 years old), and the level of ketonic derivatives was higher in younger individuals (less than 55 years old) with myocardial infarction and with both myocardial infarction and hypothyroidism. This proves the intensification of oxidative stress in both presented diseases, both among the elderly and younger individuals. The highest level of aldehydic and ketonic derivatives of oxidative modification of proteins was noted among individuals with myocardial infarctions and hypothyroidism with low physical activity and among non-smokers who suffer from hypothyroidism and additionally suffered myocardial infarctions, which may indicate an increase in oxidative stress at these diseases, regardless of physical activity and smoking. The highest level of aldehydic derivatives was noted in the group of individuals with myocardial infarction and hypothyroidism with myocardial infarction in family history, which may indicate an increase in oxidative stress in both diseases, especially in this studied group. The highest level of oxidative modification of proteins was noted among individuals with myocardial infarction and hypothyroidism, individuals with thyroid diseases in their family history, as well as those with no thyroid diseases in their family history. This proves the intensification of oxidative stress in both presented diseases, regardless of the factor of thyroid diseases in the family history. Conclusions. In the course of myocardial infarction, the level of aldehydic derivatives of oxidatively modified proteins is affected by gender, while the level of ketonic derivatives of oxidatively modified proteins is affected by the presence of a myocardial infarction in the family history. The level of aldehydic derivatives of oxidative modification of proteins in individuals with hypothyroidism is influenced by low physical activity and age over 55, while the level of ketonic derivatives of oxidative modification of proteins is affected by the gender of the individuals. In the course of myocardial infarction and hypothyroidism, the level of aldehydic derivatives of protein oxidative modification is affected by age and physical activity, while the level of ketonic derivatives of protein oxidative modification is affected by the age of individuals.

Insulin Resistance Among Children and Adolescents with Subclinical Hypothyroidism: A Case-Control Study

Background: Subclinical hypothyroidism (SCH) is marked by elevated thyroid-stimulating hormone (TSH) levels while maintaining normal thyroxine levels. Although the link between insulin resistance (IR) and overt hypothyroidism is well-established, less is known about this relationship in children and adolescents with SCH. Objectives: This study aimed to explore the association between insulin resistance and SCH in individuals aged 4 to 18 years. Methods: In this case-control study, 30 patients with SCH aged 4 - 18 from the Endocrinology Clinic at Imam Reza Hospital, Shiraz, Iran, were chosen as the case group through convenient sampling. Additionally, 30 healthy children and adolescents from the same clinic were randomly selected as controls. Exclusion criteria included positive Anti-TPO, goiter, previous thyroid disease, systemic diseases, chronic or acute diseases, diabetes, and a BMI ≥ 85%. Levels of TSH, insulin, fasting blood sugar (FBS), triglycerides, cholesterol, low-density lipoprotein, and high-density lipoprotein were compared between the groups. Data were analyzed using SPSS 25. Results: The study found that levels of FBS, insulin, and Homeostatic Model Assessment for IR (HOMA-IR) were significantly higher in the SCH group than in the control group. There was a significant correlation between TSH levels and both insulin levels and IR in the SCH group. Subclinical hypothyroidism was found to significantly increase the risk of developing IR among pediatric patients compared to healthy controls. Conclusions: Overall, our findings indicate a positive correlation between TSH levels and IR in children with SCH. Additionally, HOMA-IR levels were significantly higher with elevated TSH in the SCH group compared to healthy children. It is recommended that IR be evaluated and treated timely in SCH patients to prevent future complications.

The Effect of Bariatric Surgery on Subclinical Hypothyroidism Patients in Shiraz

The Effect of Bariatric Surgery on Subclinical Hypothyroidism Patients in Shiraz

Prevalence of Thyroid Disorder in First Trimester of Pregnancy, Study from Lumbini Province Nepal

INTRODUCTION Thyroid disorder is the second most common endocrine disorder of pregnancy. The most common thyroid disorder is hypothyroidism which often goes undiagnosed during pregnancy without screening. It has influence in maternal and fetal outcome of pregnancy. The objective of this study is to determine the prevalence of thyroid disorder in the first trimester of pregnancy. MATERIAL AND METHODSThis was cross-sectional observational study conducted for a period of 6 months (Jan - June 2022) at Universal College of Medical Sciences, Bhairahawa, Nepal. All the pregnant women in their first trimester who came for antenatal check-up in gynae OPD was included after taking consent. RESULTSTotal 393 cases were evaluated. 58% were primigravida and 42% were multigravida. Mean age was 26 years with minimum 17 years and maximum 41 years. Majority of cases were of the age group 20 to 30 years 76.6%. Thyroid disorder noted in 21.3%. Hypothyroidism found in 18.6% with overt hypothyroidism in 12.8% and subclinical hypothyroidism in 5.8%. Hyperthyroidism noted in 2.7% with overt hyperthyroidism in 1.5% and subclinical hyperthyroidism in 1.2%. CONCLUSIONThyroid disorder in pregnancy in common health problem in first trimester in pregnancy. Early diagnosis and treatment is needed to reduce complications associated with this endocrine disorder of pregnancy.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Impact of hormone replacement therapy on cardiovascular risk in patients with hypothyroidism: a systematic review

Hypothyroidism, which is developed in 4-10 % of the population, and subclinical hypothyroidism found in more than 10 % of people which are highly associated with cardiovascular pathophysiology at some level. Hypothyroidism, which is the most frequent endocrine disorder with a lack of enough thyroid hormones, presents a wide range of cardiovascular complications, including coronary artery disease, heart failure, and dyslipidemia. Thyroid hormone replacement therapy, particularly levothyroxine (LT4), continues to be the central management of hypothyroidism, which aims to restore euthyroidism and other cardiac comorbidities as well as relieving symptoms. Nonetheless, the complex interworking of thyroid function and cardiovascular health requires a detailed clarification of the processes associated with disease development and drug therapy. Hypothyroidism triggers a chain of cardiovascular alterations such as aberrant lipid metabolism, endothelial dysfunction, and lessened cardiac contractility primarily by lowering the thyroid hormone level. Besides, these modifications eventually lead to raised rates of atherosclerosis, myocardial infarction, and heart failure. LT4 replacement therapy achieves normalization of hyperthyroidism with the replacement of thyroid hormone deficiency, which restores the cardiovascular system to normal by doing so. LT4 modulates lipid metabolism, improves endothelial function, and stimulates myocardial contractility via several different mechanisms. LT4 therapy acts on systemic inflammation and oxidation to accentuate the protective effects of the cardiovascular system. Apart from this, there is an increasing awareness about the use of new thyroid hormone formulations, like LH4, in the therapy of hypothyroidism. LH4, the thyromimetic compound, demonstrated a similar binding affinity at the thyroid hormone receptor as T3 (triiodothyronine) but with better tissue selectivity and more metabolic stability. Clinical trials have proven the potency of LH4 in lowering symptoms of hypothyroidism, for example, fatigue, weight gain which are leading cause of cardiovascular disorders. LH4 administration has been safe for up to six months, and only mild adverse effects have been reported when it is used more than a year.

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

BackgroundThyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.MethodsA systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.ResultsSix articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.ConclusionsThis systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.Systematic review registrationPROSPERO CRD42022308006

The effect of periodontal status on the TSH and FT4 levels

Background: Some bacteria and viruses cause thyroid gland inflammation. Periodontal diseases lead to the production of numerous bacteria in the mouth that spread to other tissues and organs, causing infection in those sites. This investigation’s goal was to the correlation between thyroid abnormalities with periodontal disorders. Methods: The research study was carried out on 96 patients who provided blood samples from the total of 1012 applicants who enrolled to the periodontology clinic. The patients were categorized into 4 categories based on their age: (i) ages ranging 0-20, (ii) ages ranging 21-40, (iii) ages ranging 41–60, and (iv) ages over 61. In addition, they were additionally divided into three groups according to both TSH and FT4 levels: The TSHa and FT4a group included patients with below-normal values, the TSHb and FT4b group included patients with normal TSH and FT4 values, and the TSHc and FT4c group included patients with above-normal TSH and FT4 values. The statistical analysis was performed using SPSS 21. Frequency analysis and the Mann-Whitney U Analyses were utilized for statistical analysis., and the level of significance was set at P&lt;0.05. Results: The median TSH and FT4 levels of the patients were 1.98±1.28 mIU/L and 1.19±0.32 mIU/L, in that order there were no significant statistical differences seen in TSH and FT4 levels between genders or age groups. According to their FT4 and TSH levels, 7.3% of the patients had subclinical hypothyroidism and 4.2% had subclinical hyperthyroidism. In total, 11.5% of the patients had thyroid dysfunction. Conclusion: The results indicated that thyroid dysfunction was present in a remarkably high proportion of patients (11.5%).

Clinicopathological Evaluation of Thyroid Dysfunction in Women with Abnormal Uterine Bleeding

Introduction: Abnormal uterine bleeding describes any variation from normal bleeding patterns in nonpregnant, reproductive-aged women beyond menarche lasting for at least 6 months. Regular cyclic menstruation results the choreographed relationship between the endometrium and its regulating factors. Any type of disturbance between the regulatory mechanism of pituitary ovarian axis or pelvic diseases results in abnormal uterine bleeding. Thyroid hormones play a key role in the menstrual and reproductive function of women. It is recognized universally that menstrual disturbances may accompany clinical alterations in thyroid function. Objectives: To evaluate the thyroid dysfunction in patients with abnormal uterine bleeding. Materials and Methods: This cross sectional study was conducted in Department of obstetrics &amp; gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from April 2023 to December 2023. Women with abnormal uterine bleeding were included in the study. Sample was selected by purposive sampling. Sample size was 100. Detail demographic data were collected from the informant and recorded in structured case report form. Clinical examination and relevant investigation were done meticulously. Data was collected by using a semi-structured questionnaire. Data was processed and analysed with the help of computer program SPSS and Microsoft excel. Quantitative data expressed as mean and standard deviation and qualitative data as frequency and percentage. Result was presented in the form of tables, pie chart, graphs, bar diagrams, histogram &amp; charts etc. Results: In this study, the maximum numbers of cases (43.0%) were between 26-35 years age group. Mean age was 29.57 ± 8.27 years. Large numbers of respondents came from urban area (58%). On evaluation of types &amp; causes of AUB, maximum patient belongs to AUB-L (leiomyoma) group (53%) followed by AUB-A (adenomyosis) (28%); AUB-P (polyp) (8%); AUB-O (ovulatory) (9%) and AUB-M (malignancy) (2%). Present study showed that prevalence of thyroid disorders is 26% in AUB patients. The prevalence of Hypothyroidism was 18% and Hyperthyroidism was 8%. Thyroid dysfunction is associated with menstrual abnormalities in females of all age groups. Conclusion: Abnormal uterine bleeding has a strong association with thyroid disorders. The most common type of disorder is subclinical hypothyroidism. Thus, all patient of AUB must be evaluated for thyroid dysfunction. Medicine Today 2023 Vol.36 (1): 1-6

Thyroid Hormone Status in Children Taking Antiepileptic Drugs (AEDs): An Experience in a Tertiary Care Hospital of Bangladesh.

Introduction: Antiepileptic drugs (AEDs) may alter thyroid hormone homeostasis at the level of biosynthesis, release, transport, metabolism and excretion of thyroid hormones. The purpose of the study was to see the thyroid hormone status in children with epilepsy treating with common antiepileptic drugs. Materials &amp; Method: The cross-sectional study was carried out in department of pediatric neurology, National Institute of Neurosciences and Hospital (NINS), Dhaka. One hundred and sixty epileptic children aged 1 year to 14 years who were on monotherapy or polytherapy with the most commonly used Antiepileptic drugs (AEDs) for at least 6 months or more were enrolled. Serum TSH and FT4 were measured in all selected patients with early morning serum sample. Result: Nearly one third of study subjects had thyroid dysfunction, most of which were Subclinical hypothyroidism (SCH). The frequency of SCH was 29.2% in carbamazepine(CBZ), 50% in oxcabazepine (OXC), 28.6% in phenobarbitone(PHB) and 13% in valproic acid (VPA) treated epileptic children. No child was found to have subclinical hypothyroidism with topiramate and ethosuximide monotherapy. Antiepileptic drugs (AEDs) monotherapy or polytherapy had no significant difference in alteration on thyroid hormone level. Use of CBZ for long duration significantly altered thyroid function. Doses of Antiepileptic drugs (AEDs) didn’t show any significant thyroid dysfunction. Conclusion: Commonly used Antiepileptic drugs (AEDs) in children with epilepsy were associated with alteration of thyroid hormones, most commonly subclinical hypothyroidism. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 58-64

The Importance of Treating Subclinical Hypothyroidism in Patients With Immune Thrombocytopenia: A Case Report

The Importance of Treating Subclinical Hypothyroidism in Patients With Immune Thrombocytopenia: A Case Report

Study of Thyroid Function Tests in Patients with Metabolic Syndrome

Study of Thyroid Function Tests in Patients with Metabolic Syndrome

Model-Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial.

Levothyroxine is one of the most prescribed drugs in the western world. Dosing is challenging due to high-interindividual differences in effective dosage and the narrow therapeutic window. Model-informed precision dosing (MIPD) using machine learning could assist general practitioners (GPs), but no such models exist for primary care. Furthermore, introduction of decision-support algorithms in healthcare is limited due to the substantial gap between developers and clinicians' perspectives. We report the development, validation, and a clinical simulation trial of the first MIPD application for primary care. Stable maintenance dosage of levothyroxine was the model target. The multiclass model generates predictions for individual patients, for different dosing classes. Random forest was trained and tested on a national primary care database (n = 19,004) with a final weighted AUC across dosing options of 0.71, even in subclinical hypothyroidism. TSH, fT4, weight, and age were most predictive. To assess the safety, feasibility, and clinical impact of MIPD for levothyroxine, we performed clinical simulation studies in GPs and compared MIPD to traditional prescription. Fifty-one GPs selected starting dosages for 20 primary hypothyroidism cases without and then with MIPD 2 weeks later. Overdosage and underdosage were defined as higher and lower than 12.5 μg relative to stable maintenance dosage. MIPD decreased overdosage in number (30.5 to 23.9%, P < 0.01) and magnitude (median 50 to 37.5 μg, P < 0.01) and increased optimal starting dosages (18.3 to 30.2%, P < 0.01). GPs considered lab results more often with MIPD and most would use the model frequently. This study demonstrates the clinical relevance, safety, and effectiveness of MIPD for levothyroxine in primary care.