Final Diagnosis in Children with Subclinical Hypothyroidism and Mutation Analysis of the Thyroid Peroxidase Gene (TPO)
- 1 January 2009
- journal article
- clinical trial
- Published by Walter de Gruyter GmbH in Journal of Pediatric Endocrinology and Metabolism
- Vol. 22 (9), 845-51
- https://doi.org/10.1515/jpem.2009.22.9.845
Abstract
To determine the final diagnosis of patients with subclinical hypothyroidism (SCH), and to perform mutation screening of the thyroid peroxidase gene (TPO). Infants with SCH without an identified etiology were included in the study. Patients with thyroid dysgenesis were excluded. Children > or = 2 years of age, and still on L-thyroxine (LT4) treatment underwent a diagnostic algorithm. After LT4 was discontinued for 4 weeks, thyroid function tests (TFT) were obtained. A perchlorate discharge test (PDT) was performed in patients with normal thyroid ultrasound but abnormal TFT. Sequence analysis of TPO was studied in all children who underwent a PDT. Forty-eight patients (23 males and 25 females) completed the trial. Among these children, 19 (39.5%) had transient SCH, and 29 (60.5%) had permanent SCH. Among patients with permanent SCH, 19 had thyroid hypoplasia, six had partial iodide organification defect with positive PDT, and four had other dyshormonogenesis with negative PDT. Mean LT4 dose before the medication ceased was 1.2 +/- 0.5 microg/kg/day in transient cases, and 1.7 +/- 0.4 in those with permanent SCH (p < 0.05). No TPO mutation was detected. However, in five patients, seven different previously known TPO polymorphisms were detected: c.102C > G, L4L; > A, A576A; c.2088C > T, D666D; c.2263A > C, T725P; c.2630 T >C, V847A. LT4 treatment should be stopped after the age of 2 years in infants with SCH without a definite pathology of the thyroid gland to exclude cases with transient hypothyroidism. Additionally, we should consider particularly thyroid gland hypoplasia, and also partial defects in iodide organification in infants with SCH.Keywords
This publication has 16 references indexed in Scilit:
- Definitive diagnosis in children with congenital hypothyroidismThe Journal of Pediatrics, 2004
- Thyroperoxidase Gene Mutations in Congenital Goitrous Hypothyroidism with Total and Partial Iodide Organification DefectThyroid®, 2003
- Inactivating Mutations in the Gene for Thyroid Oxidase 2 (THOX2) and Congenital HypothyroidismNew England Journal of Medicine, 2002
- Three-year follow-up of borderline congenital hypothyroidismThe Journal of Pediatrics, 2000
- Thyroid Gland Volume and Urinary Iodine Excretion in Children 6-11 Years Old in an Endemic AreaJournal of Pediatric Endocrinology and Metabolism, 2000
- Pendred syndrome: evidence for genetic homogeneity and further refinement of linkage.Journal of Medical Genetics, 1997
- Thyrotropin-releasing hormone stimulation tests in infantsJournal of Clinical Endocrinology & Metabolism, 1993
- Defective Organification of Iodide Causing Hereditary Goitrous HypothyroidismThyroid®, 1993
- A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studiesNucleic Acids Research, 1991
- Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase geneBiochemistry, 1989