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Journal of Pediatric Endocrinology &... Oct 2022Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4...
OBJECTIVES
Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants.
METHODS
This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed.
RESULTS
One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 μg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 μg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 μg/kg/day, p=0.02) and the only relevant factor for predicting P-CH.
CONCLUSIONS
Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.
Topics: Congenital Hypothyroidism; Humans; Hyperthyroidism; Iatrogenic Disease; Infant; Prevalence; Retrospective Studies; Thyrotoxicosis; Thyrotropin; Thyroxine
PubMed: 36100363
DOI: 10.1515/jpem-2022-0152 -
Clinical Endocrinology Oct 2022Development and differentiation of the thyroid gland is directed by expression of specific transcription factors in the thyroid follicular cell which mediates hormone... (Review)
Review
Development and differentiation of the thyroid gland is directed by expression of specific transcription factors in the thyroid follicular cell which mediates hormone biosynthesis. Membrane transporters are rate-limiting for cellular entry of thyroid hormones (TH) (T4 and T3) into some tissues, with selenocysteine-containing, deiodinase enzymes (DIO1 and DIO2) converting T4 to the biologically active hormone T3. TH regulate expression of target genes via hormone-inducible nuclear receptors (TRα and TRβ) to exert their physiological effects. Primary congenital hypothyroidism (CH) due to thyroid dysgenesis may be mediated by defects in thyroid transcription factors or impaired thyroid stimulating hormone receptor function. Dyshormonogenic CH is usually due to mutations in genes mediating thyroidal iodide transport, organification or iodotyrosine synthesis and recycling. Disorders of TH signalling encompass conditions due to defects in membrane TH transporters, impaired hormone metabolism due to deficiency of deiodinases and syndromes of Resistance to thyroid hormone due to pathogenic variants in either TRα or TRβ. Here, we review the genetic basis, pathogenesis and clinical features of congenital, dysgenetic or dyshormonogenic hypothyroidism and disorders of TH transport, metabolism and action.
Topics: Humans; Hypothyroidism; Iodide Peroxidase; Signal Transduction; Thyroid Hormones; Transcription Factors
PubMed: 35999191
DOI: 10.1111/cen.14817 -
Endocrine Oct 2019Hypothyroidism is the most frequent pregnancy-related thyroid dysfunction, including overt and subclinical hypothyroidism. Studies show that even mild hypothyroidism may... (Review)
Review
Hypothyroidism is the most frequent pregnancy-related thyroid dysfunction, including overt and subclinical hypothyroidism. Studies show that even mild hypothyroidism may eventuate in adverse gestational outcomes and intellectual impairment of offspring. Women with overt hypothyroidism (OH) must be treated by levothyroxine (LT4) pre- and during pregnancy, however, it is controversial that when and how to initiate LT4 therapy and further optimize dosing so that pregnant women and their offspring may truly benefit. In the review we will analyze the changes in thyroid hormone requirements in pregnant women, the timing of LT4 treatment and adjustment of LT4 dose according to etiology in patients with hypothyroidism during pregnancy, and adjustment of LT4 after delivery.
Topics: Animals; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Thyroxine
PubMed: 31617164
DOI: 10.1007/s12020-019-02044-2 -
Medicina (Kaunas, Lithuania) Oct 2023: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations...
: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. : A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21-79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. : Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively ( < 0.05, chi-square test). : In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.
Topics: Humans; Infant; Child, Preschool; Child; Thyroid Diseases; Hypothyroidism; Hyperthyroidism; Thyroid Hormones; Lupus Erythematosus, Systemic; Autoantibodies
PubMed: 38003960
DOI: 10.3390/medicina59111911 -
Medicine Oct 2023To investigate the causal relationship between hypothyroidism and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale...
To investigate the causal relationship between hypothyroidism and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study (GWAS) were used. Genetic loci that were independent of each other and associated with hypothyroidism and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting (IVW) was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between hypothyroidism and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. IVW results showed an OR (95% CI) of 1.07 (1.01-1.14), P = .024, indicating that hypothyroidism is a risk factor for a frozen shoulder. And no pleiotropy was found by the test, and sensitivity analysis also showed robust results. This study used 2-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with hypothyroidism, suggesting that active control of hypothyroidism may reduce the occurrence of frozen shoulder.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Causality; Bursitis; Hypothyroidism
PubMed: 37904373
DOI: 10.1097/MD.0000000000035650 -
Archives of Disease in Childhood Jun 2022
Topics: Endocrinology; Humans; Hypothyroidism
PubMed: 34772661
DOI: 10.1136/archdischild-2021-323051 -
Journal of the American Academy of... May 2020Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction...
Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction (primary hypothyroidism). We present a case of symptomatic quetiapine-induced hypothyroidism due to hypothalamic/pituitary gland dysfunction (central [secondary] hypothyroidism).
Topics: Humans; Hypothyroidism; Quetiapine Fumarate
PubMed: 32036034
DOI: 10.1016/j.jaac.2020.01.018 -
Journal of Basic and Clinical... Aug 2020Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The... (Review)
Review
Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The prevalence of hypothyroidism in developed countries is around 4-5%, whereas it is about 11% in India, only 2% in the UK, and 4·6% in the USA. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and thyroid-stimulating hormone, imaging studies, procedures, and histological findings. The treatment of choice for hypothyroidism is levothyroxine, however; in this review article, we have discussed the epidemiology, etiology, clinical sign and symptoms, diagnosis, complications, and management of hypothyroidism in modern medicine and a comparative treatment by the Unani system of medicine (USM). In the USM, the main emphasis of the principle of treatment () is to correct the abnormal constitution () and alter the six prerequisites for existence () to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes different drugs, dosages form, and regimens.
Topics: Female; Humans; Hypothyroidism; Male; Medicine, Unani; Thyroid Hormones; Thyrotropin; Thyroxine
PubMed: 32776903
DOI: 10.1515/jbcpp-2020-0121 -
Clinical Endocrinology Dec 2022Although an association between type 1 diabetes (T1D) and hypothyroidism has been found in multiple observational studies, whether T1D plays a causal role in the...
OBJECTIVES
Although an association between type 1 diabetes (T1D) and hypothyroidism has been found in multiple observational studies, whether T1D plays a causal role in the development of hypothyroidism remains uncertain. Therefore, this Mendelian randomization (MR) study aimed to investigate the causal association between T1D and hypothyroidism.
METHODS
Independent single-nucleotide polymorphisms associated with T1D with genome-wide significance were selected as instrumental variables from a large genome-wide association study (GWAS) of T1D. Hypothyroidism GWAS summary statistics were obtained from the Thyroidomics Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for estimating the effect of the exposure on the outcome. We also used MR-Egger, the weighted median method, MR-Robust, and other methods to confirm the results.
RESULTS
T1D had a positive causal association with hypothyroidism [IVW, odds ratio (OR) = 1.083, 95% confidence interval (CI), 1.046-1.122; p < .001]. MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.006; p = .295). The causal association was verified in an independent validation set (IVW, OR = 1.099, 95% CI, 1.018-1.186; p = .017). The results were robust according to various MR methods, and the results of the reverse MR analysis did not support reverse causation (p > .05).
CONCLUSIONS
The MR analysis results indicated a causal association between T1D and hypothyroidism. Therefore, it is recommended that patients with T1D undergo thyroid function tests regularly to minimize the risk of undiagnosed hypothyroidism among young patients with T1D.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Diabetes Mellitus, Type 1; Polymorphism, Single Nucleotide; Hypothyroidism
PubMed: 35927830
DOI: 10.1111/cen.14801 -
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