Genetic Analysis in Children with Transient Thyroid Dysfunction or Subclinical Hypothyroidism Detected on Neonatal Screening

Satoh, Mari; Aso, Keiko; Ogikubo, Sayaka; Ogasawara, Atsuko; Saji, Tsutomu

doi:10.1297/cpe.18.95

Cited by 12 publications

(10 citation statements)

References 25 publications

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“…Mutations in thyroid peroxidase (TPO), DUOX2 and TSH receptor genes may cause permanent or transient CH (8,9,10,43). In the present study, thyroid imaging showed normal, enlarged, or hypoplastic gland in situ in 46% of the patients with permanent CH, indicating a higher possibility of recessively inherited genetic defects in our region where consanguineous marriages were relatively frequent.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, genetic background might also have contributed to the development of transient thyroid dysfunction in our cohort. Given that iodine intake may alter the phenotype of TPO and DUOX2 mutations causing iodine organification defects (8,43,44,45), it is even possible that iodine deficiency in our region might have increased the expressivity of gene defects. In Turkey, permanent CH due to dyshormonogenesis is mainly caused by TPO mutations (46), but there is no study investigating the genetic background in transient CH.…”

Section: Discussionmentioning

confidence: 99%

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Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Kara

Gunindi²,

Yılmaz³

et al. 2016

Jcrpe

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Objective: Prevalence of congenital hypothyroidism (CH) in Turkey at birth was reported to be as high as 1:650 in 2008-2010. Incidence rates of permanent and transient CH separately are unknown due to lack of follow-up data. We aimed to evaluate the impact of transient hypothyroidism on increasing incidence of CH and to determine the natural course and the clinical, biochemical, and imaging characteristics of transient CH.Methods: Baseline and follow-up data of the infants with CH detected at screening in six provinces in the Black Sea Region were analyzed retrospectively during a time period covering the years 2008-2010.Results: Among 138 cases (48% female), 16 (12%) showed transient hyperthyrotropinemia which resolved without intervention. Of the treated 122 cases, 63 (52%) had transient CH. While its frequency was 35% in 2008, it increased to 56% in 2009-2010, following a lowering of the thyroid stimulating hormone cutoff value. The frequency was higher in inland provinces than in coast (67% vs. 43%; p=0.01).Clinical characteristics of permanent and transient cases were similar except female-to-male sex ratios (1.5:1 vs. 0.6:1; p=0.02). L-thyroxine was discontinued in 70% of transient cases before 3 years of age at a median age of 19 (2-36) months. The only indication for early discontinuation of treatment was a low L-thyroxine dose, which was 1.25±0.27 µg/kg/day at withdrawal time.Conclusion: Our regional follow-up data showed that more than half of newborns with primary CH had transient thyroid dysfunction. In the majority of cases, discrimination between transient and permanent CH can be made before age 3 years, as indicated by cessation of L-thyroxine treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Kara

Gunindi²,

Yılmaz³

et al. 2016

Jcrpe

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“…CH is classified into CH requiring continuous treatment; and transient and subclinical CH (definitions given below) ( 1 , 6 , 8 , 9 , 10 , 11 , 12 ). However, it can be difficult to differentiate the two types because transient CH may involve a morphological or genetic abnormality of the thyroid gland ( 13 , 14 , 15 , 16 , 17 , 18 ).…”

Section: Definition Of Congenital Hypothyroidismmentioning

confidence: 99%

Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision)

Nagasaki

Minamitani

Anzo

et al. 2015

Clin Pediatr Endocrinol

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Purpose of developing the guidelines: Mass screening for congenital hypothyroidism started in 1979 in Japan, and the prognosis for intelligence has been improved by early diagnosis and treatment. The incidence was about 1/4000 of the birth population, but it has increased due to diagnosis of subclinical congenital hypothyroidism. The disease requires continuous treatment, and specialized medical facilities should make a differential diagnosis and treat subjects who are positive in mass screening to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, new findings on prognosis and problems in the adult phase have emerged. Based on these new findings, the 1998 guidelines were revised in the current document (hereinafter referred to as the Guidelines). Target disease/conditions: Primary congenital hypothyroidism. Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring patients to pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients.

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“…In general, it is expected that DH is inherited in an autosomal recessive manner. However, recent studies have reported notable exceptions and complex genotype-phenotype correlations [ 12 13 14 15 16 17 18 19 ]. For instance, biallelic and triallelic mutations in DUOX2 cause permanent CH, whereas a monoallelic mutation also suffices to cause transient CH [ 14 20 ].…”

Section: Introductionmentioning

confidence: 99%

DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population

Park

Kim

et al. 2016

Ann Lab Med

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BackgroundMost cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH.MethodsA total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced.ResultsThe mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH.ConclusionsThe mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.

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Genetic Analysis in Children with Transient Thyroid Dysfunction or Subclinical Hypothyroidism Detected on Neonatal Screening

Cited by 12 publications

References 25 publications

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Transient Congenital Hypothyroidism in Turkey: An Analysis on Frequency and Natural Course

Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision)

DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population

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