Abstract:Background: The incidence of congenital hypothyroidism (CH) has increased over the years, and many predictors for detecting newborns with transient forms (TCH) as early as possible have been considered. Methods: All newborns diagnosed with primary CH and eutopic gland in the Piedmont region of Italy in the period of January 2014–June 2019 were enrolled and re-evaluated at the age of 2 years. Results: 105 newborns were diagnosed with CH during the study period. Dyshormonogenesis was observed in 55/105. At re-ev… Show more
“…Traditionally, the etiology of CH has been attributed to TD in 75%–85% of cases, while TDH accounts for 15%–25% 4 . However, the results of several studies conducted worldwide to evaluate the incidence of CH and TDH in the recent decade vary considerably 5 .…”
Section: Introductionmentioning
confidence: 99%
“…3 Traditionally, the etiology of CH has been attributed to TD in 75%-85% of cases, while TDH accounts for 15%-25%. 4 However, the results of several studies conducted worldwide to evaluate the incidence of CH and TDH in the recent decade vary considerably. 5 Some studies report an increasing trend in CH or TDH, as in India and Japan, 5,6 while others have shown no such trend, as in Finland.…”
Thyroid dyshormonogenesis (TDH) is responsible for 15%–25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in‐house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.
“…Traditionally, the etiology of CH has been attributed to TD in 75%–85% of cases, while TDH accounts for 15%–25% 4 . However, the results of several studies conducted worldwide to evaluate the incidence of CH and TDH in the recent decade vary considerably 5 .…”
Section: Introductionmentioning
confidence: 99%
“…3 Traditionally, the etiology of CH has been attributed to TD in 75%-85% of cases, while TDH accounts for 15%-25%. 4 However, the results of several studies conducted worldwide to evaluate the incidence of CH and TDH in the recent decade vary considerably. 5 Some studies report an increasing trend in CH or TDH, as in India and Japan, 5,6 while others have shown no such trend, as in Finland.…”
Thyroid dyshormonogenesis (TDH) is responsible for 15%–25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in‐house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.
Context
Clinical course and need for long-term L-thyroxine (LT4) therapy of congenital hypothyroidism (CH) with gland in situ (GIS) remain unclear.
Objective
To describe the clinical history of CH with GIS and evaluate the proportion of patients who can suspend therapy during follow-up.
Design and setting
Retrospective evaluation of patients followed at referral regional center for CH of Pisa.
Patients
77 patients with confirmed primary CH and GIS after positive neonatal screening were included. All children started LT4 at CH confirm.
Interventions
At 3 years of age, 55 children underwent a clinical re-evaluation after withdrawal of therapy with hormonal examinations, imaging of the thyroid gland with ultrasonography and 123-iodine with perchlorate discharge test. Subsequent periodic controls of thyroid function were executed and, when possible, a new attempt to stop LT4 was performed. Adequate follow-up data (at least 6 months after treatment suspension trial) were available for 49 patients.
Results
Among the 55 patients who were reassessed, 18 (32.7%) were euthyroid. Considering subsequent follow-up, 49% of patients were no longer treated and 51% were taking therapy. No differences in neonatal parameters were observed between the two groups; LT4 dose before the last trial off medication was higher in permanent CH (p 0.016).
Conclusion
Monitoring of thyroid function in children with CH and GIS is necessary to evaluate the need for substitution and avoid overtreatment. Even if therapy can be suspended, patients need to be monitored because apparently normal thyroid function may decline several months after withdrawal of LT4.
Objectives
An increased incidence of congenital hypothyroidism (CH) has been described worldwide over the years. In this study, we aimed to investigate the epidemiologic characteristics of CH, the iodine status in Guangzhou, China and to investigate which factors might influence the CH incidence during the period 2010–2020.
Methods
We retrospectively reviewed all cases of CH detected by newborn screening during the period 2010–2020. CH was classified as either suspected thyroid dyshormonogenesis (SDH) or thyroid dysgenesis (TD) based on thyroid ultrasound at first diagnosis. Patients were re-evaluated after 4 weeks of L-thyroxine withdrawal at age of 2–3 years to confirm the diagnosis of permanent CH (PCH) or transient CH (TCH).
Results
From 2010 to 2020, 1,655 patients with CH were confirmed from 2,400,383 newborns (1:1,450). The CH incidence increased from 1:2,584 in period [2010–2014] to 1:1,086 in period [2015–2020]. Among the 1,337 patients with thyroid ultrasound, 84.29% were SDH whereas 15.71% had TD. Further analysis revealed that more SDH (78.32%) were TCH whereas more TD (87.12%) turned to be PCH. The proportion of blood spot thyrotropin values >5 mIU/L ranged from 8.03 to 20.46%, indicating iodine deficiency. The prevalence of preterm infants increased from 5.50% in period [2010–2014] to 7.06% in period [2015–2020] (p<0.001).
Conclusions
In the past decade, the CH incidence has increased progressively. SDH was the majority of CH, most of which were TCH, while most patients with TD were PCH. The increased incidence might be mainly due to iodine deficiency and increased rates of preterm infants in our study.
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