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Italian Journal of Pediatrics Feb 2018Aim of this commentary is to report current knowledges on the main clinical and metabolic abnormalities which might be observed in children with longstanding and... (Comparative Study)
Comparative Study Review
Aim of this commentary is to report current knowledges on the main clinical and metabolic abnormalities which might be observed in children with longstanding and untreated subclinical hypothyroidism (SH) and to comment the most recent views about natural evolution of thyroid function in the cases with either idiopathic or Hashimoto's thyroiditis-related SH. On the basis of these preliminary remarks, the essential guidelines for an appropriate and tailored management of SH children are also proposed.
Topics: Adolescent; Age Factors; Child; Chronic Disease; Clinical Decision-Making; Female; Humans; Hypothyroidism; Male; Prognosis; Risk Assessment; Severity of Illness Index; Thyroid Function Tests; Thyroid Gland
PubMed: 29454373
DOI: 10.1186/s13052-018-0462-4 -
Cancer Feb 2022Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study...
BACKGROUND
Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study examined the prevalence of and risk factors for primary hypothyroidism and its associations with physical, neurocognitive, and psychosocial outcomes.
METHODS
This was a retrospective study with a cross-sectional health outcome analysis of an established cohort comprising 2965 survivors of childhood cancer (52.8% male; median current age, 30.9 years, median time since cancer diagnosis, 22.3 years). Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between primary hypothyroidism and cancer-related risk factors, cardiovascular disease risk factors, frailty, neurocognitive and QOL outcomes, social attainment, and subsequent thyroid carcinoma. Associations between serum free thyroxine and thyrotropin levels at assessment and health outcomes were explored.
RESULTS
The prevalence of primary hypothyroidism was 14.7% (95% CI, 13.5%-16.0%). It was more likely in females (OR, 1.06; 95% CI, 1.03-1.08), was less likely in non-Whites (OR, 0.96; 95% CI, 0.93-0.99), was associated with thyroid radiotherapy (higher risk at higher doses), and was more common if cancer was diagnosed at an age ≥ 15.0 years versus an age < 5 years (OR, 1.05; 95% CI, 1.01-1.09). Primary hypothyroidism was associated with frailty (OR, 1.54; 95% CI, 1.05-2.26), dyslipidemia (OR, 1.52; 95% CI, 1.14-2.04), impaired physical QOL (OR, 1.66; 95% CI, 1.12-2.48), and having health care insurance (OR, 1.51; 95% CI, 1.07-2.12).
CONCLUSIONS
Primary hypothyroidism is common in survivors and is associated with unfavorable physical health and QOL outcomes. The impact of thyroid hormone replacement practices on these outcomes should be investigated further.
Topics: Adolescent; Adult; Cancer Survivors; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Hypothyroidism; Leukemia, Myeloid, Acute; Male; Prevalence; Quality of Life; Retrospective Studies; Risk Factors
PubMed: 34643950
DOI: 10.1002/cncr.33969 -
Frontiers in Endocrinology 2023Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.
BACKGROUND
Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.
OBJECTIVES
This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.
METHODS
genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks.
RESULT
Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, = 3.03×10) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3.
CONCLUSION
This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.
Topics: Humans; Alopecia Areata; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypothyroidism
PubMed: 38292771
DOI: 10.3389/fendo.2023.1309620 -
Deutsches Arzteblatt International Jun 2017The prevalence of latent/subclinical hypothyroidism is between 3% and 10%, according to epidemiologic studies that have been carried out in the USA, the United Kingdom,... (Review)
Review
BACKGROUND
The prevalence of latent/subclinical hypothyroidism is between 3% and 10%, according to epidemiologic studies that have been carried out in the USA, the United Kingdom, and Denmark. As persons with latent hypo - thyroidism are often asymptomatic, the diagnosis is often made incidentally in routine laboratory testing.
METHODS
This review is based on a selective search in PubMed for publications on the diagnosis and treatment of latent hypothyroidism. All pertinent articles and guidelines published from 1 January 2000 to 31 July 2016 were included.
RESULTS
The diagnosis of latent hypothyroidism is generally assigned after repeated measurement of a TSH concentration above 4.0 mU/L in a person whose fT4 concentration is in the normal range. The most common cause is autoimmune thyroiditis, which can be detected by a test for autoantibodies. L-thyroxin supplementation is a controversial matter: its purpose is to prevent the development of overt hypothyroidism, but there is a danger of overtreatment, which increases the risk of fracture. To date, no benefit of L-thyroxin supplementation has been demonstrated with respect to morbidity and mortality, health-related quality of life, mental health, cognitive function, or reduction of overweight. There is, however, evidence of a beneficial effect on cardiac function in women, and on the vascular system. At present, treatment is generally considered indicated only if the TSH level exceeds 10.0 mU/L.
CONCLUSION
Limited data are available on the relevant clinical endpoints and undesired side effects of supplementation therapy. Physicians should advise patients about the indications for such treatment on an individual basis after due consideration of the risks and benefits.
Topics: Adult; Female; Humans; Hypothyroidism; Pregnancy; Prevalence; Quality of Life; Reference Values; Thyrotropin; Young Adult
PubMed: 28683860
DOI: 10.3238/arztebl.2017.430 -
Deutsches Arzteblatt International Apr 2022Neonatal screening in Germany currently comprises 19 congenital diseases, 13 of which are metabolic diseases. Approximately one in 1300 newborns suffers from one of... (Review)
Review
BACKGROUND
Neonatal screening in Germany currently comprises 19 congenital diseases, 13 of which are metabolic diseases. Approximately one in 1300 newborns suffers from one of these target diseases. Early diagnosis and treatment enable the affected children to undergo better development and even, in many cases, to have a normal life.
METHODS
This review is based on pertinent publications retrieved by a selective search in the PubMed and Embase databases.
RESULTS
Positive screening findings are confirmed in approximately one out of five newborns. The prompt evaluation of suspected diagnoses is essential, as treatment for some of these diseases must be initiated immediately after birth to prevent longterm sequelae. The most commonly identified diseases are primary hypothyroidism (1:3338), phenylketonuria/hyperphenylalaninemia (1 : 5262), cystic fibrosis (1 : 5400), and medium-chain acyl-CoA dehydrogenase deficiency (1 : 10 086). Patient numbers are rising as new variants of the target diseases are being identified, and treatments must be adapted to their heterogeneous manifestations. Precise diagnosis and the planning of treatment, which is generally lifelong, are best carried out in a specialized center.
CONCLUSION
Improved diagnosis and treatment now prolong the lives of many patients with congenital diseases. The provision of appropriate long-term treatment extending into adulthood will be a central structural task for screening medicine in the future.
Topics: Acyl-CoA Dehydrogenase; Cystic Fibrosis; Early Diagnosis; Germany; Humans; Hypothyroidism; Infant, Newborn; Lipid Metabolism, Inborn Errors; Neonatal Screening; Phenylketonurias
PubMed: 35140012
DOI: 10.3238/arztebl.m2022.0075 -
Frontiers in Immunology 2023Observational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship...
BACKGROUND
Observational studies have demonstrated an association between primary sclerosing cholangitis (PSC) and thyroid dysfunction (TD). However, the causal relationship between PSC and TD remains uncertain. The purpose of this study is to investigate the causal associations and specific direction between these two conditions. Gaining insight into the potential causal relationship between PSC and TD is valuable for elucidating the pathogenesis of PSC and for devising innovative approaches for the prevention and treatment of PSC and its associated complications.
METHODS
We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal association between PSC and TD, such as autoimmune thyroid disease (AITD), thyroid cancer (TC), thyroid stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), among others. PSC was the exposure variable, while TD was the outcome variable. To identify suitable instrumental variables (IVs), we utilized genome-wide association study (GWAS) datasets to select potential candidate single-nucleotide polymorphisms (SNPs). The primary statistical approach employed was the inverse-variance weighted (IVW) method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy.
RESULTS
We found that the causal associations between genetically predicted PSC and Graves' disease (GD), hyperthyroidism (IVW OR=1.230, 95%CI: 1.089-1.389, P=0.001; IVW OR=1.001, 95%CI: 1.000-1.002, P=0.000) were statistically significant. The reverse MR analysis indicated that genetic susceptibility to hyperthyroidism (P=0.000) and hypothyroidism (p=0.028) might be the risk of PSC. There was no statistically significant causal association observed between PSC and other TD (IVW P>0.05), with the exception of GD, hyperthyroidism, and hypothyroidism as determined through bidirectional two-sample analysis. To ensure the reliability of our findings, additional sensitivity analyses were conducted, including the leave-one-out (LOO) test, heterogeneity test, and pleiotropic test.
CONCLUSION
In this study, we conducted an investigation into the causal association between PSC and TD. Our findings indicate that PSC significantly elevates the susceptibility to GD and hyperthyroidism from a statistical perspective. These results shed light on the etiology of PSC and have implications for the management of patients with PSC.
Topics: Humans; Cholangitis, Sclerosing; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Hyperthyroidism; Hypothyroidism; Graves Disease
PubMed: 37928559
DOI: 10.3389/fimmu.2023.1276459 -
The Science of the Total Environment Apr 2023While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy...
BACKGROUND
While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely impact offspring development.
OBJECTIVES
We evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.
METHODS
We measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal-Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hypothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypothyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex.
RESULTS
A 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence interval [CI]: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio [aOR]: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI: 1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: -8.42; 95 % CI: -15.33, -1.50).
DISCUSSION
Fluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
Topics: Male; Female; Humans; Pregnancy; Child, Preschool; Fluorides; Drinking Water; Canada; Hypothyroidism; Thyroid Hormones; Pregnancy Complications; Thyrotropin
PubMed: 36764861
DOI: 10.1016/j.scitotenv.2022.161149 -
Ethiopian Journal of Health Sciences Nov 2023Children with sickle cell anaemia have been reported to have potential risk of hypothyroidism from chronic blood transfusions and probable thyroid tissue ischaemia....
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Humans; Anemia, Sickle Cell; Hypothyroidism; Child; Male; Cross-Sectional Studies; Female; Nigeria; Thyrotropin; Child, Preschool; Prevalence; Adolescent; Thyroxine; Triiodothyronine; Thyroid Hormones; Infant
PubMed: 38784480
DOI: 10.4314/ejhs.v33i6.6 -
Frontiers in Endocrinology 2023Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from...
INTRODUCTION
Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link.
METHODS
We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism.
RESULTS
MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism.
DISCUSSION
Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypothyroidism; Causality; Obesity
PubMed: 38260160
DOI: 10.3389/fendo.2023.1287463 -
Thyroid : Official Journal of the... Sep 2021Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal...
Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on hemostasis, coagulation, and fibrinolysis are unknown. In a two-sample Mendelian randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism ( = 134,641), normal-range thyrotropin (TSH; = 54,288) and free thyroxine (fT4) ( = 49,269), hyperthyroidism ( = 51,823), and thyroid peroxidase antibody positivity ( = 25,821) on coagulation (activated partial thromboplastin time, von Willebrand factor [VWF], factor VIII [FVIII], prothrombin time, factor VII, fibrinogen) and fibrinolysis (D-dimer, tissue plasminogen activator [TPA], plasminogen activator inhibitor-1) from the CHARGE Hemostasis Consortium ( = 2583-120,246). Inverse-variance-weighted random effects were the main MR analysis followed by sensitivity analyses. Two-sided < 0.05 was nominally significant, and < 0.0011[ = 0.05/(5 exposures × 9 outcomes)] was Bonferroni significant for the main MR analysis. Genetically increased TSH was associated with decreased VWF [β(SE) = -0.020(0.006), = 0.001] and with decreased fibrinogen [β(SE) = -0.008(0.002), = 0.001]. Genetically increased fT4 was associated with increased VWF [β(SE) = 0.028(0.011), = 0.012]. Genetically predicted hyperthyroidism was associated with increased VWF [β(SE) = 0.012(0.004), = 0.006] and increased FVIII [β(SE) = 0.013(0.005), = 0.007]. Genetically predicted hypothyroidism and hyperthyroidism were associated with decreased TPA [β(SE) = -0.009(0.024), = 0.024] and increased TPA [β(SE) = 0.022(0.008), = 0.008], respectively. MR sensitivity analyses showed similar direction but lower precision. Other coagulation and fibrinolytic factors were inconclusive. In the largest genetic studies currently available, genetically increased TSH and fT4 may be associated with decreased and increased synthesis of VWF, respectively. Since Bonferroni correction may be too conservative given the correlation between the analyzed traits, we cannot reject nominal associations of thyroid traits with coagulation or fibrinolytic factors.
Topics: Autoantibodies; Biomarkers; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Case-Control Studies; Fibrinolysis; Genetic Predisposition to Disease; Genome-Wide Association Study; Hemostasis; Humans; Hyperthyroidism; Hypothyroidism; Mendelian Randomization Analysis; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Thyrotropin; Thyroxine; von Willebrand Factor
PubMed: 34210154
DOI: 10.1089/thy.2021.0055