Emerging research themes in maternal hypothyroidism: a bibliometric exploration.

Background: Hypothyroidism, a prevalent endocrine disorder, carries significant implications for maternal and infant health, especially in the context of maternal hypothyroidism. Despite a gradual surge in recent research, achieving a comprehensive understanding of the current state, focal points, and developmental trends in this field remains challenging. Clarifying these aspects and advancing research could notably enhance maternal-infant health outcomes. Therefore, this study employs bibliometric methods to systematically scrutinize maternal hypothyroidism research, serving as a reference for further investigations. Objective: Through bibliometric analysis, this study seeks to unveil key research focus areas, developmental trends, and primary contributors in Maternal Hypothyroidism. The findings offer insights and recommendations to inform future research endeavors in this domain. Methods: Literature metrics analysis was performed on data retrieved and extracted from the Web of Science Core Collection database. The analysis examined the evolution and thematic trends of literature related to Maternal Hypothyroidism. Data were collected on October 28, 2023, and bibliometric analysis was performed using VOSviewer, CiteSpace, and the Bibliometrix software package, considering specific characteristics such as publication year, country/region, institution, authorship, journals, references, and keywords. Results: Retrieved from 1,078 journals, 4,184 articles were authored by 18,037 contributors in 4,580 institutions across 113 countries/regions on six continents. Maternal Hypothyroidism research publications surged from 44 to 310 annually, a 604.54% growth from 1991 to 2022. The USA (940 articles, 45,233 citations), China Medical University (82 articles, 2,176 citations), and Teng, Weiping (52 articles, 1,347 citations) emerged as the most productive country, institution, and author, respectively. "Thyroid" topped with 233 publications, followed by "Journal of Clinical Endocrinology & Metabolism" (202) with the most citations (18,513). "Pregnancy" was the most cited keyword, with recent high-frequency keywords such as "outcome," "gestational diabetes," "iodine intake," "preterm birth," "guideline," and "diagnosis" signaling emerging themes in Maternal Hypothyroidism. Conclusions: This study unveils developmental trends, global collaboration patterns, foundational knowledge, and emerging frontiers in Maternal Hypothyroidism. Over 30 years, research has predominantly focused on aspects like diagnosis, treatment guidelines, thyroid function during pregnancy, and postpartum outcomes, with a central emphasis on the correlation between maternal and fetal health.

ASSESSMENT OF OSTEOPONTIN, SCLEROSTIN, AND OSTEOCALCIN LEVELS IN PATIENTS WITH HYPOTHYROIDISM ON MEDICAL THERAPY.

Thyroid hormones are critical regulators of bone maintenance in adulthood and play an important part in the development of bones. They also play a function in the formation of bones. Childhood hypothyroidism leads to delayed skeletal development, limited linear growth, and impaired bone mineral accumulation. This research aims to assess the serum concentration of sclerostin, osteocalcin, and osteopontin in women diagnosed with hypothyroidism. Additionally, it seeks to examine the impact of medical treatment on the levels of sclerostin, osteocalcin, and osteopontin in individuals with hypothyroidism. This research examined a total of 180 women, divided into three groups: 70 women before treatment, 70 women after treatment, and 40 control subjects. The age range of the participants was between 15 and 54 years. The participants in this research are categorized into three distinct groups: The first cohort consisted of 70 women diagnosed with hypothyroidism, as confirmed by medical professionals. The second group consisted of 70 women who had undergone treatment for hypothyroidism. The research included a control group consisting of healthy women with no family history of thyroid illness. These women were in good health and their ages were similar to those of the women with hypothyroidism. According to the presented data show a decrease in the mean of the serum level of sclerostin, and osteocalcin in hypothyroidism women before and after treatment compared with the control group (13.4±4.9 versus 19.8±5.1 and 21.5±5.0), (9.8±4.7 versus 14.35±12.63 and 15.20±14.73), respectively. The result was significant (p<0.01), with no differences in osteopontin levels between study groups. It was concluded that the sclerostin, and osteocalcin decreased in women with hypothyroidism before treatment in comparison with women after treatment and healthy women, while Furthermore no differences in Osteopontin levels between the three groups.

Relationship of thyroid dysfunction and its manifestations in diabetes mellitus patients in the Kingdom of Saudi Arabia.

OBJECTIVE: Both diabetes mellitus (DM) and thyroid dysfunction (TD) are endocrinopathies that are frequently inclined to coexist in patients. Most studies avoid explicitly supporting or opposing testing thyroid function for diabetic patients as a baseline. The association between hypothyroidism and diabetes is considerable when assessing thyroid functions in diabetic individuals based on clinical suspicion. Therefore, this study aimed to assess the relationship between thyroid dysfunction and its manifestations in DM patients in the Kingdom of Saudi Arabia. SUBJECTS AND METHODS: The study included 301 DM subjects. A questionnaire divided into two sections was administered to all participants. The first section involved questions about diabetes control, monitoring, and disease severity. The second section included questions about thyroid disease and the 14-item Hypothyroidism Clinical Prediction (HCP) score we created for our research. The HCP score was obtained by summing up all discrete scores for different symptoms of hypothyroidism. ROC curve analysis was used to assess the predicted hypothyroidism cases based on the most precise cut-off point for the HCP overall score (highest sensitivity and specificity). HCP discriminant ability for detecting hypothyroid cases was assessed considering the Area Under the Curve (AUC) as a measurement. RESULTS: Almost 53 (17.6%) diabetes mellitus subjects were previously diagnosed with hypothyroidism. Comparatively, regarding the given cut-off point, the total number of predicted hypothyroidism cases using the HCP score was 149 (49.5%). The most reported symptoms included tiredness (75%), followed by irritability (72%), and difficulty in losing weight (65%). Hypothyroidism was detected/predicted among 60.1% of female diabetics vs. 44.2% of males with recorded statistical significance (p=.006). CONCLUSIONS: This study further proves a significant association between diabetes and hypothyroidism in Saudi Arabia. We recommend periodic screening for thyroid dysfunction in the diabetic population in specific cases; since some patients with diabetes are more likely to have hypothyroidism based on their clinical presentation.

Prevalence of Thyroid Dysfunction in Type 2 Diabetes Mellitus.

The level of thyroid hormones is often changed in uncontrolled diabetic patients. Screening for Thyroid dysfunction (TD) among patients with Type 2 Diabetes mellitus (T2DM) should be performed considering the increased prevalence of thyroid disorders. This cross-sectional comparative study was conducted in outpatient department of Endocrinology and Medicine, Mymensingh Medical College Hospital, Mymensingh (MMCH) from 1st March 2020 to 30th August 2021. One hundred (100) patients with type 2 diabetes along with 100 (hundred) non-diabetic controls of same age group were enrolled in the study. After taking clinical data, patients were investigated to estimate Fasting plasma glucose (FPG), serum free tri-iodothyronine (FT3), free thyroxin (FT4) and thyroid stimulating hormone (TSH) level to see thyroid dysfunction. Patients were selected with purposive sampling. Thyroid dysfunction was found to be more in T2DM (15.0%) in comparison with non-diabetic controls (5.0%) and this difference was statistically significant (p=0.018). In both diabetic and non-diabetic groups, subclinical hypothyroidism and hypothyroidism were the most common thyroid dysfunction. Thyroid dysfunction was found more in 40-60 years that suggests the prevalence of thyroid dysfunction are increasing in diabetic patients with advancing age. Thyroid dysfunction was found more among overweight and obese patient in both groups. Mean BMI was found higher among diabetic patient with thyroid dysfunction. Logistic regression showed significant association of Thyroid dysfunction with age >50 years and high FPG level. We found thyroid dysfunction was more prevalent in patients with T2DM than non-diabetics. So, screening for thyroid dysfunction among type 2 diabetic patients by estimating Serum TSH, FT4 level should be performed.

Possible association between subclinical hypothyroidism and age at menopause in Colombian women.

OBJECTIVE: To evaluate the association between subclinical hypothyroidism with early menopause, premature menopause, and last menstrual bleeding before the natural age of menopause. METHODS: This was a cross-sectional study conducted in 643 postmenopausal women aged 40-69 years. Groups were formed according to last menstrual episode: ≥45 [Natural age at menopause], 40-44 and [Early menopause], <40 [Premature menopause], and <45 [last menstrual episode before the natural age of menopause]. The Zulewski scale was applied to identify manifestations related to hypothyroidism and subclinical hypothyroidism, diagnosed with a serum TSH > 4.5 µIU/mL plus T4-free between 0.7 and 1.9 ng/dL. RESULTS: It was found that 24.4% had the last menstrual episode before the natural age of menopause, 18.6% had early menopause, and 5.7% had premature menopause. Subclinical hypothyroidism was diagnosed in 4.5% of patients. Among women with subclinical hypothyroidism, there was a higher frequency of early menopause, premature menopause, and last menstrual episode before the natural age of menopause, than in women without subclinical hypothyroidism (p < 0.05). Paresthesia (50%) and dry skin (40.7%) were the most reported hypothyroidism-related manifestations. Early menopause, premature menopause, and last menstrual episode before the natural age of menopause were associated with subclinical hypothyroidism, OR: 3.37 [95% CI: 1.40-8.10], OR: 4.31 [95% CI: 1.24-14.97], and OR: 3.57 [95% CI: 1.57-8.10], respectively. CONCLUSIONS: The last menstrual episode before the natural age of menopause, early menopause, and premature menopause were significantly associated with a higher chance of subclinical hypothyroidism.

Association of autoimmune and allergic diseases with senile cataract: a bidirectional two-sample Mendelian randomization study.

Background: Many observational studies have been reported that patients with autoimmune or allergic diseases seem to have a higher risk of developing senile cataract, but the views are not consistent. In order to minimize the influence of reverse causality and potential confounding factors, we performed Mendelian Randomization (MR) analysis to investigate the genetic causal associations between autoimmune, allergic diseases and senile cataract. Methods: Single nucleotide polymorphisms associated with ten common autoimmune and allergic diseases were obtained from the IEU Open genome-wide association studies (GWAS) database. Summary-level GWAS statistics for clinically diagnosed senile cataract were obtained from the FinnGen research project GWAS, which consisted of 59,522 individuals with senile cataracts and 312,864 control individuals. MR analysis was conducted using mainly inverse variance weighted (IVW) method and further sensitivity analysis was performed to test robustness. Results: As for ten diseases, IVW results confirmed that type 1 diabetes (OR = 1.06; 95% CI = 1.05-1.08; p = 2.24×10-12), rheumatoid arthritis (OR = 1.05; 95% CI = 1.02-1.08; p = 1.83×10-4), hypothyroidism (OR = 2.4; 95% CI = 1.42-4.06; p = 1.12×10-3), systemic lupus erythematosus (OR = 1.02; 95% CI = 1.01-1.03; p = 2.27×10-3), asthma (OR = 1.02; 95% CI = 1.01-1.03; p = 1.2×10-3) and allergic rhinitis (OR = 1.07; 95% CI = 1.02-1.11; p = 2.15×10-3) were correlated with the risk of senile cataract. Celiac disease (OR = 1.04; 95% CI = 1.01-1.08; P = 0.0437) and atopic dermatitis (OR = 1.05; 95% CI = 1.01-1.10; P = 0.0426) exhibited a suggestive connection with senile cataract after Bonferroni correction. These associations are consistent across weighted median and MR Egger methods, with similar causal estimates in direction and magnitude. Sensitivity analysis further proved that these associations were reliable. Conclusions: The results of the MR analysis showed that there were causal relationships between type 1 diabetes, rheumatoid arthritis, hypothyroidism, systemic lupus erythematosus, asthma, allergic rhinitis and senile cataract. To clarify the possible role of autoimmune and allergy in the pathophysiology of senile cataract, further studies are needed.

Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study.

Background: The causal association between thyroid dysfunction (including hyperthyroidism and hypothyroidism) and sepsis is controversial in previous studies. Therefore, we used Mendelian randomization (MR) to explore the causal association between hyperthyroidism or hypothyroidism and the susceptibility to four distinct subtypes of sepsis (streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis). Methods: In our research, we conducted two-sample Mendelian randomization (MR) analyses utilizing publicly available genome-wide association studies (GWAS) data from Sakaue et al. and the Finnish database to investigate the potential causal associations between hyperthyroidism, hypothyroidism, and each of the four distinct subtypes of sepsis, in addition to reverse MR analyses of the positive results to examine the existence of reverse causality. Results: Genetic hypothyroidism was causally related to the development of asthma-associated pneumonia or sepsis (ORIVW: 1.097, 95% CI: 1.024 to 1.174, P = 0.008); hypothyroidism was significantly associated with the development of other sepsis (ORIVW: 1.070, 95% CI: 1.028 to 1.115, P < 0.001). In addition, sensitivity analysis substantiated the robustness of these two MR findings, with no evidence of horizontal pleiotropy observed (P > 0.05). MR Egger regression analysis demonstrated no heterogeneity between instrumental variables (IVs). Inverse MR results confirmed no reverse causality between hypothyroidism and asthma-associated pneumonia or sepsis, or between hypothyroidism and other sepsis. The findings of this study also unveiled that there is no evidence of a causal link between hypothyroidism and the development of streptococcal sepsis or puerperal sepsis. Additionally, the research provided evidence indicating the absence of a causal relationship between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis. Conclusions: This study identified a causal link between hypothyroidism and the occurrence of asthma-associated pneumonia or sepsis, and other sepsis, but not with the development of streptococcal sepsis and puerperal sepsis. Moreover, our findings did not reveal any causal association between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns.

Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. Objective: To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. Design, Setting, and Participants: In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Exposure: Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Main Outcomes and Measures: The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. Results: A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. Conclusions and Relevance: In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.

Diagnoses of obstetric and postpartum thyroid disease: a Danish validation study.

Different diagnoses of thyroid disease are available in the 10th International Classification of Diseases (ICD-10), but the validity of diagnoses related to obstetric and postpartum thyroid disease is unknown. This was a retrospective cohort study of all patients in the North Denmark Region with a diagnosis of postpartum thyroiditis (PPT) (ICD-10: O905) from 2016 to 2019 or obstetric thyroid disease in 2019 (ICD-10: O992B (hypothyroidism) or O992C (hyperthyroidism)) registered in the Danish National Hospital Register. Information from nationwide registers and medical records were used to assess the validity. Among patients with an O905-diagnosis (n = 40), abnormal thyroid function test results were seen in all cases. A total of eight patients (20.0%) were positive for thyrotropin receptor antibodies postpartum, however, in low titers, and PPT was verified in 39 of 40 cases (97.5%). Altogether 45 of 50 patients with an O992B-diagnosis (90.0%) correctly had hypothyroidism, whereas hyperthyroidism was found in 25 of 39 patients with an O992C-diagnosis (64.1%). This is the first study to validate ICD-10 diagnoses of obstetric and postpartum thyroid disease. A high validity was seen for PPT (O905) and obstetric hypothyroidism (O992B), whereas for obstetric hyperthyroidism (O992C), the diagnosis could not be verified in one third of the cases.

Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study.

Background: Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. Methods: We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity. Results: Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; P = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, P = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships. Conclusion: This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.

Growth and endocrinopathies among children with ß-Thalassemia major treated at Dubai Thalassemia centre.

BACKGROUND: ß-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre. METHODS: A total of 105 children and adolescents were included in this retrospective observational study. RESULTS: 39 children and 66 adolescents' data were analyzed. Females composed 51.3% (n = 20) of children and 53.0% (n = 35) of adolescents. Pretransfusion hemoglobin below 9 gm/dl was observed in 10.8% (n = 4) and 10.6% (n = 7) in children and adolescents, respectively. The mean age of menarche was 13.5 years. Among all study participants, 22.6% (n = 14) had normal height velocity whereas 37.1% (n = 23) had reduced height velocity in one year and 40.3% (n = 25) had reduced height velocity in two consecutive years. The proportion of children and adolescents showing reduced height velocity was significantly higher in females compared to the males (90.6% versus 63.3%, respectively, Chi-square = 6.597, p-value = 0.010). Although none of the study participants had diabetes mellitus, 26.1% (n = 12/46) had pre-diabetes. Elevated TSH was observed in 14.7% (n = 5) children and 8.1% (n = 5) adolescents while low FT4 was reported in one child and one adolescent. CONCLUSION: Of all endocrinopathies seen among children and adolescents with BTM, growth delay remains the main concern for this group of patients. Effective treatment is key to further reducing endocrinopathies. Although the sample size is limited, we postulate that the low percentage of endocrinopathies among children with BTM treated at Dubai thalassemia center and the low level of pretransfusion anemia reflect the effective transfusion and chelation at the center.

Burden of Thyroid Dysfunction Among Type 2 Diabetes Mellitus Patients in South East Nigeria with Emphasis on its Prevalence and Pattern of Presentation: A Case-Controlled Study.

BACKGROUND: Studies from different parts of the world on thyroid dysfunction have shown it to be widespread in patients with type 2 diabetes mellitus (T2DM); however, there is insufficient local data to support this observation. AIM: To determine the burden of thyroid dysfunction among patients with T2DM at a Tertiary Hospital in Southeast Nigeria with emphasis on its prevalence and pattern of presentation. METHODS: Four hundred and seventy-two subjects were recruited for the study. All the subjects (100%) were of African descent. Three hundred and fifty-four (354) of them were patients with T2DM, while 118 subjects who did not have T2DM served as the controls. This study is a descriptive cross-sectional study involving patients with type 2 diabetes mellitus attending the Diabetes Clinic or receiving treatment in the Medical Wards. Subjects were recruited using systematic sampling. The first patient was selected by simple random sampling, and subsequently, every consecutive subject was selected. Blood samples were tested for HbA1c, fT3, fT4, thyrotropin, and thyroid stimulating hormone. Socio-demographic information was retrieved from patient medical records. We used the Student's t-test for statistical comparison of quantitative variables such as weight, height, blood pressure, serum TSH, and serum T3; while for comparison of proportions, we used a Chi-squared test. We set a p-value of less than 0.05 to be statistically significant. RESULTS: Females formed the majority of the study population accounting for 56.5% of the type 2 DM patients and 62.7% of the controls. We observed that the mean age of the type 2 DM patients was 57.5 (±9.3) years, which was similar to the mean age of controls: 57.7±8.9 (p=0.17). We also observed that the mean age at diagnosis of DM was 54±7.6 years, while the mean duration of DM for all the type 2 DM patients was 6.5±2.8 years. We observed that in patients with T2DM, the prevalence of thyroid dysfunction was 12.4% and among the controls, a prevalence of 1.7% was observed (P <0.05). Females formed the majority (75%) of T2DM patients with thyroid dysfunction and hypothyroidism was the most common type of thyroid dysfunction (93.2%) observed in this study. CONCLUSION: The prevalence of thyroid dysfunction in T2DM patients in this study was 12.4% which was high compared to 1.7% observed in the controls (P = 0.001). The majority of those who had thyroid dysfunction were females. About 9 in 10 of all subjects with thyroid dysfunction had hypothyroidism.

CONTEXTE: Des études menées dans différentes régions du monde sur la dysfonction thyroïdienne ont montré qu'elle est répandue chez les patients atteints de diabète sucré de type 2 (T2DM) ; cependant, il existe des données locales insuffisantes pour étayer cette observation. OBJECTIF: Déterminer la charge de la dysfonction thyroïdienne chez les patients atteints de T2DM dans un hôpital tertiaire du sud-est du Nigeria, en mettant l'accent sur sa prévalence et son modèle de présentation. MÉTHODES: Quatre cent soixante-douze sujets ont été recrutés pour l'étude. Tous les sujets (100 %) étaient d'origine africaine. Trois cent cinquante-quatre (354) d'entre eux étaient des patients atteints de T2DM, tandis que 118 sujets ne présentaient pas de T2DM et servaient de témoins. Cette étude est une étude transversale descriptive impliquant des patients atteints de diabète sucré de type 2 fréquentant la clinique du diabète ou recevant un traitement dans les services de médecine. Les sujets ont été recrutés par échantillonnage systématique. Le premier patient a été sélectionné par échantillonnage aléatoire simple, et par la suite, chaque sujet consécutif a été sélectionné. Des échantillons de sang ont été testés pour l'HbA1c, le fT3, le fT4 et la thyrotropine, hormone stimulant la thyroïde. Les informations sociodémographiques ont été récupérées à partir des dossiers médicaux des patients. Nous avons utilisé le test t de Student pour la comparaison statistique des variables quantitatives telles que le poids, la taille, la pression artérielle, la TSH sérique et la T3 sérique ; tandis que pour la comparaison des proportions, nous avons utilisé un test du Chi-carré. Nous avons fixé une valeur de p inférieure à 0,05 pour être statistiquement significative. RÉSULTATS: Les femmes formaient la majorité de la population étudiée, représentant 56,5 % des patients atteints de DM de type 2 et 62,7 % des témoins. Nous avons observé que l'âge moyen des patients atteints de DM de type 2 était de 57,5 (±9,3) ans, ce qui était similaire à l'âge moyen des témoins: 57,7±8,9 (p=0,17). Nous avons également observé que l'âge moyen au diagnostic du DM était de 54±7,6 ans, tandis que la durée moyenne du DM pour l'ensemble des patients atteints de DM de type 2 était de 6,5±2,8 ans. Nous avons observé que chez les patients atteints de T2DM, la prévalence de la dysfonction thyroïdienne était de 12,4 % et parmi les témoins, une prévalence de 1,7 % a été observée (P <0,05). Les femmes formaient la majorité (75 %) des patients atteints de T2DM avec une dysfonction thyroïdienne et l'hypothyroïdie était le type le plus courant de dysfonction thyroïdienne (93,2 %) observé dans cette étude. CONCLUSION: La prévalence de la dysfonction thyroïdienne chez les patients atteints de T2DM dans cette étude était de 12,4 %, ce qui était élevé par rapport à 1,7 % observé chez les témoins (P = 0,001). La majorité de ceux qui avaient une dysfonction thyroïdienne étaient des femmes. Environ 9 sujets sur 10 présentant une dysfonction thyroïdienne avaient une hypothyroïdie. MOTS-CLÉS: Dysfonction thyroïdienne; Diabète sucré de type 2; Hypothyroïdie; Sud-est du Nigeria; Prévalence.

A machine learning approach for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma undergoing tomotherapy.

The purpose of this study was to establish an integrated predictive model that combines clinical features, DVH, radiomics, and dosiomics features to predict RIHT in patients receiving tomotherapy for nasopharyngeal carcinoma. Data from 219 patients with nasopharyngeal carcinoma were randomly divided into a training cohort (n = 175) and a test cohort (n = 44) in an 8:2 ratio. RIHT is defined as serum thyroid-stimulating hormone (TSH) greater than 5.6 µU/mL, with or without a decrease in free thyroxine (FT4). Clinical features, 27 DVH features, 107 radiomics features and 107 dosiomics features were extracted for each case and included in the model construction. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the most relevant features. The eXtreme Gradient Boosting (XGBoost) was then employed to train separate models using the selected features from clinical, DVH, radiomics and dosiomics data. Finally, a combined model incorporating all features was developed. The models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. In the test cohort, the area under the receiver operating characteristic curve (AUC) for the clinical, DVH, radiomics, dosiomics and combined models were 0.798 (95% confidence interval [CI], 0.656-0.941), 0.673 (0.512-0.834), 0.714 (0.555-0.873), 0.698 (0.530-0.848) and 0.842 (0.724-0.960), respectively. The combined model exhibited higher AUC values compared to other models. The decision curve analysis demonstrated that the combined model had superior clinical utility within the threshold probability range of 1% to 79% when compared to the other models. This study has successfully developed a predictive model that combines multiple features. The performance of the combined model is superior to that of single-feature models, allowing for early prediction of RIHT in patients with nasopharyngeal carcinoma after tomotherapy.

THE RELATION OF THYROID DISTURBANCE AND ISCHEMIC HEART DISEASE IN IRAQI PATIENTS.

This study conducted in Baghdad focused on patients with coronary heart disease admitted to three hospitals. The study included 60 Iraqi patients with coronary heart disease and a control group of 30 healthy individuals. Blood samples were collected from both groups after fasting. The study analyzed the demographic characteristics of the patients and control group, including age groups, sex distribution, and BMI. The majority of patients had hypertension, while 58.33% had diabetes. The study found that IHD patients had significantly higher T3 and T4 levels compared to the control group. However, there was no significant difference in TSH levels. The study also examined thyroid function parameters among different age groups and found no significant differences in individuals with hypothyroidism. The highest prevalence of hyperthyroidism was among individuals with hypertension, while the highest spread of hypothyroidism was among individuals with diabetes. The study observed significant differences in mean HbA1c levels among the three groups, with the highest levels in patients with hypothyroidism. In conclusion, this study suggests potential alterations in thyroid function associated with ischemic heart disease and emphasizes the need for further research on the clinical implications and underlying mechanisms involved.

Thyroid hormone deprival and TSH/TSHR signaling deficiency lead to central hypothyroidism-associated intestinal dysplasia.

BACKGROUND: Central hypothyroidism (CH) is characterized by low T4 levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr-/- mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling. METHODS: The morphological characteristics of intestines were determined by HE staining, periodic acid-shiff staining, and immunohistochemical staining. T4 was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T4-injected Tshr-/- mice. KEY FINDINGS: Tshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr-/- mice. Tshr-/- mice with early-life T4 injections had more early goblet cells and impaired metabolism compared to Tshr+/+ mice. SIGNIFICANCE: TH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism.

Association of pharmacogenomic, clinical and behavioural factors with oral levothyroxine (LT-4) dose of hypothyroid patients in Sri Lanka: a matched case control study.

BACKGROUND: Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka. METHOD: This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis. DISCUSSION: Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.

The link between underactive thyroid and leg oedema.

There is an established link between hypothyroidism and leg oedema. This article presents a case study of a female known to have an underactive thyroid gland who developed symptoms and was referred to a local Lindsay Leg Club.