Detecting congenital hypothyroidism with newborn screening: the relevance of thyroid-stimulating hormone cutoff values

Silvestrin, Stela Maris; Leone, Cláudio; Leone, Cléa Rodrigues

doi:10.1016/j.jped.2016.07.006

Cited by 15 publications

(8 citation statements)

References 21 publications

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“… Wassner and Brown (2015) reported that the apparent incidence of CH has more than doubled in recent years ranging from 1:2800 to 1:1400. Meanwhile, countries, such as the United States ( Mitchell et al, 2011 ), Canada ( Deladoëy et al, 2011 ), New Zealand ( Heather et al, 2017 ), Scotland ( Mansour et al, 2017 ), Brazil ( Silvestrin et al, 2017 ), reported slight differences. In our study, there was no significant difference in the incidence of CH between males and females, consistent with the study by Zhao et al (2016) .…”

Section: Discussionmentioning

confidence: 99%

Newborn Screening and Molecular Profile of Congenital Hypothyroidism in a Chinese Population

Long

Yang

et al. 2018

Front. Genet.

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To review the characteristics of newborn screening of congenital hypothyroidism (CH), we reviewed the newborn screening data, including the levels of blood spot thyroid-stimulating hormone (TSH), and serum TSH and free thyroxine (FT4), of all newborn infants who accepted the newborn screening program during the last 14 years. In total, 437,342 newborn infants underwent CH screening and 192 infants were diagnosed with CH and the incidence of CH was 1:2278. The positive rate of the initial screening was 0.96%, and the positive predictive value was 4.8%. We also designed a target sequencing panel including 13 causative genes: DUOX2, TG, TPO, TSHR, TTF1, TTF2, PAX8, NKX2-5, GNAS, THRA, TSHB, IYD and SLC5A5, to identify the spectrum and prevalence of disease-causing gene mutations in Chinese CH patients. CH-causing genes were detected by targeted next-generation sequencing in 106 CH infants. A total of 132 mutations were identified in 69 cases (65.1%). Of these 132 mutations, 92 (69.70%), 28 (21.21%), and 12 (9.09%) were related to thyroid dyshormonogenesis, thyroid dysgenesis, and thyrotropin resistance, respectively. Mutations in CH-causing genes were found mainly in DUOX2, TG and TSHR, and DUOX2 is the most gene mutation in Chinese CH patients.

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Section: Discussionmentioning

confidence: 99%

Newborn Screening and Molecular Profile of Congenital Hypothyroidism in a Chinese Population

Long

Yang

et al. 2018

Front. Genet.

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“…Overall, the incidence of CH found in the Brazilian neonatal screening is 1/2,595 to 1/4,795 (10,27) in accordance with the expected global incidence reported of 1/3,000-4,000 infants (3,6,9). ISTG was the most common etiology found in our cohort, with a rise in incidence from previously reported measures, primarily attributed to the diagnosis of milder cases of CH due to a lower TSH threshold used for screening (28).…”

Section: Genetics Findingsmentioning

confidence: 93%

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Cerqueira¹,

Ramos²,

Strappa³

et al. 2018

Archives of Endocrinology and Metabolism

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Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (7.8%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

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“…However, there are variations in the cut-off value adopted by neonatal screening programs in different countries, and even within countries, which implies a non-uniformity in the rate of retesting and pathology prevalence statistics. Therefore, in some states, the cut-off values recommended by the local screening programs were between 4.5 and 10 μIU/mL [ 14 ], well below the values recommended by the National Screening Program. Silvestrin et al (2017) suggested that a cut-off value of 5.03 μIU/mL could result in a higher sensitivity (100%) and specificity (93.7%) for the detection of CH [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in some states, the cut-off values recommended by the local screening programs were between 4.5 and 10 μIU/mL [ 14 ], well below the values recommended by the National Screening Program. Silvestrin et al (2017) suggested that a cut-off value of 5.03 μIU/mL could result in a higher sensitivity (100%) and specificity (93.7%) for the detection of CH [ 14 ]. Another study showed that a percentage of newborns with TSH values below 10 and hyperresponsiveness to the thyrotropin-releasing hormone (TRH) test was diagnosed with CH during follow-up [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…There is a consensus that RN with increased TSH values (TSH � 15 mIU/mL) must be investigated according to the screening program flowchart. However, this value is higher than that adopted by neonatal screening programs in other countries and within some countries' states [14]. In 2018, Kilberg et al suggested that US neonatal screening programs were missing newborns with mild and persistent TSH elevations, who could have CH and its health consequences, due to the lack of adequate standardization of TSH values [15].…”

Section: Introductionmentioning

confidence: 98%

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Neonatal thyrotropin levels and auditory neural maturation in full-term newborns

et al. 2021

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Objective This study aimed to look for a possible relationship between thyrotropin (TSH) values from neonatal bloodspot screening testing and newborn lower auditory pathway myelinization evaluated using the brainstem evoked response audiometry (ABR) test. Methods Sixty-two healthy full-term newborns without perinatal problems were enrolled in the study. TSH results were collected from neonatal bloodspot screening data and were below the test cut-off level (15μUI/mL). The TSH test was performed between three and seven days, and the ABR test was performed in the first 28 days of life. The newborns were divided into two groups: Group 1 (n = 35), TSH between 0 and 5μUI/mL, and group 2 (n = 27), TSH between 5 and 15μUI/mL. Data are presented as mean ± SD, median, or percentage, depending on the variable. Results Wave latency and interpeak interval values for Groups 1 and 2 were as follows: Wave I: 1.8 ± 0.1 and 1.7 ± 0.1; Wave III: 4.4 ± 0.1 and 4.4 ± 0.1; Wave V: 6.9 ± 0.1 and 6.9 ± 0.1; interval I–III: 2.6 ± 0.1 and 2.6 ± 0.1; interval I–V: 5.1 ± 0.1 and 5.1 ± 0.1; interval III–V: 2.4 ± 0.1 and 2.4 ± 0.1. There were no significant differences in ABR parameters between groups 1 and 2 (p > 0.05). Multiple regression analysis showed a slight significant negative correlation between TSH and wave I values (standardized β = −0.267; p = 0.036), without observing any relationship with the other ABR waves recorded. Conclusions This study investigated the relationship of TSH and auditory myelinization evaluated by ABR. It did not show a significant change in lower auditory pathway myelinization according to TSH levels in newborns with TSH screening levels lower than 15 μUI/mL.

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Detecting congenital hypothyroidism with newborn screening: the relevance of thyroid-stimulating hormone cutoff values

Abstract: The ROC curve confirmed that the TSHneo cutoff value of 5.0μIU/mL adopted by the Newborn Screening Program of a Brazilian state was the most appropriate for detecting congenital hypothyroidism and most likely explains the high prevalence that was found.

Cited by 15 publications

References 21 publications

Newborn Screening and Molecular Profile of Congenital Hypothyroidism in a Chinese Population

Newborn Screening and Molecular Profile of Congenital Hypothyroidism in a Chinese Population

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Neonatal thyrotropin levels and auditory neural maturation in full-term newborns

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