Severe iodine deficiency causes hypothyroidism that results in impaired somatic growth and motor development in children. Mild and moderate iodine deficiencies cause multifocal autonomous growth of thyroid, which results in thyrotoxicosis. On the other hand, iodine excess is associated with the development of hypothyroidism and thyroid autoimmunity. In areas of iodine deficiency, a sudden increase in iodine intake is associated with transient hyperthyroidism. Recent studies demonstrated that long-term thyroid function of subjects who experienced both iodine deficiency and iodine excess during childhood tended to be abnormal despite optimization of their current iodine intake. Iodine status in the Korean Peninsula is very unique because people in the Republic of Korea have been shown to have predominantly excessive iodine levels, whereas the Democratic People's Republic of Korea is known to be an iodine-deficient area. Further research is warranted to verify the optimal ranges of iodine intake and to clarify the effects of iodine intake on thyroid disorders in the Korean Peninsula.

Excessive iodine intake from BM contributed to subclinical hypothyroidism in these preterm Korean infants.

The aim of this study was to evaluate the incidence of thyroid dysfunction during valproic acid (VPA) therapy in children and adolescents with epilepsy. The serum levels of thyroid-stimulating hormone (TSH), free thyroxine, and triiodothyronine were evaluated in 61 children with epilepsy who received VPA monotherapy for more than 6 months and in 144 controls. We analyzed the effect of age, seizure type, duration of VPA treatment, dose of VPA, and serum level of VPA on thyroid function. The incidence of subclinical hypothyroidism was significantly higher in patients with VPA therapy than in controls (52.4 vs. 16.7%; p < 0.001). In addition, of the 61 patients, 5 (8.1%) exhibited TSH levels that were >10 μIU/mL. However, none of the patients and controls showed overt hypothyroidism. Serum VPA level and daily dose of VPA were correlated with TSH level. Subclinical hypothyroidism developed frequently in children and adolescents during VPA therapy.

To determine the validity of a repeat thyroid function test for preterm infants, and to investigate factors that influence thyroid function of preterm infants, thyroid functions of 105 infants born at <32 weeks' gestational age were evaluated. Initial serum free thyroxine (fT4) and thyrotropin (TSH) levels were measured during the first 10 days of life, and repeated tests were performed more than 2 weeks apart. We analyzed the effects of gestational age, systemic diseases, and nutrition on the development of thyroid dysfunction. Thirty-one infants (30%) had low fT4 levels (<0.7 ng/dL) in the absence of elevated TSH levels (<7 µU/mL). Thirteen infants (12%) had hypothyroidism (fT4 <0.7 ng/dL, TSH ≥10 µU/mL) and mean age at diagnosis was 28±17 days. Twelve infants had moderately elevated TSH (TSH 10-30 µU/mL) with normal fT4 levels after 1 week of postnatal life. The history of undergone surgical procedure which needed iodine containing disinfectants was significantly frequent in the infant with hypothyroidism and transient TSH elevation. Repeated thyroid function tests are necessary for preterm infants, even though they initially show normal thyroid function, and are especially important for infants who have been exposed to excessive or insufficient levels of iodine.

Objective: Steroidogenic acute regulatory (STAR) protein plays a crucial role in steroidogenesis, and mutations in the STAR gene cause congenital lipoid adrenal hyperplasia (CLAH). This study investigated the STAR mutation spectrum and functionally analyzed a novel STAR mutation in Korean patients with CLAH. Methods: Mutation analysis of STAR was carried out in 25 unrelated Korean CLAH patients. A region of STAR comprising exons 4-7 was cloned from human genomic DNA into an expression vector, followed by site-directed mutagenesis and transient expression in COS7 cells. The splicing pattern was analyzed by in vitro transcription, and each transcript was functionally characterized by measuring pregnenolone production in COS7 cells cotransfected with the cholesterol side chain cleavage system. Results: Mutation p.Q258X was identified in 46 of 50 alleles (92%); mutation c.653COT was detected in two alleles (4%); and mutations p.R182H and c.745-6_810del were found in one allele (2%). Reverse transcriptase-PCR products amplified from a patient heterozygous for compound c.653COT and c.745-6_810del mutation revealed multiple alternatively spliced mRNAs. In vitro expression analysis of a minigene consisting of exons 4-7 containing the c.653COT yielded two transcripts in which exon 6 or exons 5 and 6 were skipped. The encoded proteins exhibited defective pregnenoloneproducing ability. The c.745-6_810del mutation led to full and partial intron retention. Conclusions: p.Q258X is the most common STAR mutation in Korea. A previously reported c.653COT variant was found to cause aberrant splicing at the mRNA level, resulting in perturbation of STAR function. The c.745-6_810del mutation also resulted in aberrant splicing.