Congenital Hypothyroidism due to a Low Level of Maternal Thyrotropin Receptor-Blocking Antibodies

Castellnou, Solène; Bretones, Patricia; Abeillon, J.; Moret, M.; Perrin, P.; Chikh, Karim; Raverot, Véronique

doi:10.1159/000509015

Cited by 6 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regardless of the cause of CH, it is necessary to treat it in time once it is diagnosed so that the child's FT4 level reaches the normal range as soon as possible to meet the needs of growth and development [ 20 ], and most studies show that after active treatment, most children have a good prognosis and can reach the normal level of intelligence. However, a few children have neurological sequelae despite long-term, regular treatment, which may be related to maternal hypothyroidism and impaired neurological development during intrauterine fetal brain development during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Serological Characteristics, Etiological Analysis, and Treatment Prognosis of Children with Congenital Hypothyroidism

shen¹,

Ding

2022

Emergency Medicine International

View full text Add to dashboard Cite

Objective. The aim of the study is to analyze the serological features, etiology, and prognosis of congenital hypothyroidism (CH) treated with L-thyroxine sodium (L-T4). Methods. A total of 126 CH children in our hospital from June 2015 to January 2020 were selected as the research objects, and L-T4 treatment was given immediately after diagnosis. After diagnosis and 24 months of treatment, laboratory serum thyroid function-related indicators were examined, and thyroid changes were determined by ultrasound. We compared serum thyroxine levels in children with different thyroid changes, compared serum thyroid hormone levels, serum ghrelin levels, and body mass index (BMI) changes in children with CH before treatment and after 24 months of treatment, and analyzed the prognosis of treatment in children. In terms of thyroid changes in 126 CH children, 32 cases (25.40%) had a normal thyroid gland, 16 cases (12.70%) had a hypoplastic thyroid gland, 40 cases (31.75%) had an ectopic thyroid gland, 28 cases (22.22%) had an absent thyroid gland, and 10 cases (7.93%) had an enlarged thyroid gland, with an ectopic thyroid gland being the most common. In terms of serological expression of CH children, the TSH level in children with thyroid dysplasia was significantly higher than that in children with basic normal and T3 and T4 levels were significantly lower than those in children with basic normal ( P < 0.05 ). At the same time, the TSH level in children with thyroid absence, ectopic, and enlargement was increased, while thyroxine (T4) and tri-iodothyronine (T3) levels were decreased compared with those in children with thyroid dysplasia. The difference was statistically significant ( P < 0.05 ). Univariate analysis showed that there were statistically significant differences in birth weight, week of gestation at delivery, maternal age at childbirth, household registration, and a family history of thyroid disease compared between the two groups ( P < 0.05 ); multivariate logistic regression analysis showed that birth weight <2,500 g, maternal age >35 years, rural residence, and a family history of thyroid disease were risk factors for neonatal CH ( P < 0.05 ). Serum thyroid-stimulating hormone (TSH) levels, serum ghrelin levels, and the body mass index of children with CH decreased significantly, and T4 levels increased significantly after 24 months of treatment ( P < 0.05 ). Conclusion. Screening for common causes of CH is conducive to timely detection of children with CH, and L-T4 treatment can effectively improve thyroid function in children.

show abstract

Section: Discussionmentioning

confidence: 99%

Serological Characteristics, Etiological Analysis, and Treatment Prognosis of Children with Congenital Hypothyroidism

shen¹,

Ding

2022

Emergency Medicine International

View full text Add to dashboard Cite

show abstract

“…Interestingly, pathogenic variants in TSHR and PAX8 genes have been reported in patients with permanent congenital hypothyroidism showing reduced to normal-sized eutopic thyroid glands with low to absent radioiodide uptake on thyroid scintigraphy ( 29 , 30 ). Regarding the patient with transient congenital hypothyroidism, Castellnou et al ( 31 ) recently reported a case of transient congenital hypothyroidism with eutopic gland and undetectable radioiodide uptake on thyroid scintigraphy due to maternal thyrotropin receptor-blocking antibodies (TRAbs). This report highlights the importance to analyze TRAbs in hypothyroid mothers during pregnancy, which is particularly useful when congenital hypothyroidism is diagnosed in their newborns.…”

Section: Discussionmentioning

confidence: 99%

Silent but Not Harmless: A Synonymous SLC5A5 Gene Variant Leading to Dyshormonogenic Congenital Hypothyroidism

et al. 2022

View full text Add to dashboard Cite

BackgroundCongenital iodide transport defect (ITD) is an uncommon cause of dyshormonogenic congenital hypothyroidism characterized by the absence of active iodide accumulation in the thyroid gland. ITD is an autosomal recessive disorder caused by loss-of-function variants in the sodium/iodide symporter (NIS)-coding SLC5A5 gene.ObjectiveWe aimed to identify, and if so to functionally characterize, novel ITD-causing SLC5A5 gene variants in a cohort of five unrelated pediatric patients diagnosed with dyshormonogenic congenital hypothyroidism with minimal to absent 99mTc-pertechnetate accumulation in the thyroid gland.MethodsThe coding region of the SLC5A5 gene was sequenced using Sanger sequencing. In silico analysis and functional in vitro characterization of a novel synonymous variant were performed.ResultsSanger sequencing revealed a novel homozygous synonymous SLC5A5 gene variant (c.1326A>C in exon 11). In silico analysis revealed that the c.1326A>C variant is potentially deleterious for NIS pre-mRNA splicing. The c.1326A>C variant was predicted to lie within a putative exonic splicing enhancer reducing the binding of splicing regulatory trans-acting protein SRSF5. Splicing minigene reporter assay revealed that c.1326A>C causes exon 11 or exon 11 and 12 skipping during NIS pre-mRNA splicing leading to the NIS pathogenic variants p.G415_P443del and p.G415Lfs*32, respectively. Significantly, the frameshift variant p.G415Lfs*32 is predicted to be subjected to degradation by nonsense-mediated decay.ConclusionsWe identified the first exonic synonymous SLC5A5 gene variant causing aberrant NIS pre-mRNA splicing, thus expanding the mutational landscape of the SLC5A5 gene leading to dyshormonogenic congenital hypothyroidism.

show abstract

“…TSH receptor-stimulating antibodies and TSH receptor-blocking antibodies are the two types of TSH receptor antibodies. The capacity of maternal TSH receptor antibodies to penetrate the placenta results in impaired fetal thyroid function [24]. Figure 2 depicts thyroid hormone regulation in the thyroid gland of the fetus.…”

Section: Thyroid Hormone In Fetal Developmentmentioning

confidence: 99%

A Narrative Review on the Effect of Maternal Hypothyroidism on Fetal Development

Pande¹,

Anjankar²

2023

Cureus

View full text Add to dashboard Cite

The thyroid is a butterfly-shaped gland located in the human body's neck region. The thyroid produces three hormones that are essential for regulating body temperature, energy production, weight, hair and nail growth, and menstrual cycle maintenance. The production of these hormones is controlled by a feedback mechanism. Various factors cause changes in the stimulation and inhibition of these hormones, which ultimately causes either excessive release or a decrease in the levels of thyroid hormones. These causes can be physiological or pathological. One of the physiological causes is pregnancy. Pregnancy is a very complex process in which many changes occur in the body and its functioning. One of which is changes in the maternal thyroid gland. The inability to adequately adapt to the changes leads to the abnormal functioning of the thyroid gland. During pregnancy, there is a variation in the concentration of thyroid hormones which may cause a decrease in levels or inhibition in the production of thyroid hormones. This condition is called hypothyroidism. Hypothyroidism in pregnant mothers can either be gestational or may be a condition that is present way before her pregnancy. Often, gestational hypothyroidism reverts after delivery during the postpartum period but can also be present as subclinical hypothyroidism. In such cases, they pose a significant threat to development, cause growth hindrance to the infant in the womb, and cause abnormalities in the offspring in the future. Some of the changes occur in the gland because of enhancement in levels of thyroid binding globulin, increased clearance rate of iodine from the body in kidneys, altered effects in human chorionic gonadotropin hormone, and decreased consumption of iodine in meals. Iodine disbalance in maternal hypothyroidism is associated with severe health issues like cretinism and mental retardation. Thyroid hormones are crucial for the infant's neural, cognitive, and intelligence quotient development in the womb. Thus, the disturbances in the maternal hormone levels disturb typical early developmental characteristics. In the world of rapidly advancing scientific research, there are many ways in which this condition can be detected early, diagnosed correctly, and given apt and required attention and treatment for causing the least harm to the fetus and the mother.

show abstract

Congenital Hypothyroidism due to a Low Level of Maternal Thyrotropin Receptor-Blocking Antibodies

Cited by 6 publications

References 27 publications

Serological Characteristics, Etiological Analysis, and Treatment Prognosis of Children with Congenital Hypothyroidism

Serological Characteristics, Etiological Analysis, and Treatment Prognosis of Children with Congenital Hypothyroidism

Silent but Not Harmless: A Synonymous SLC5A5 Gene Variant Leading to Dyshormonogenic Congenital Hypothyroidism

A Narrative Review on the Effect of Maternal Hypothyroidism on Fetal Development

Contact Info

Product

Resources

About