Abstract.The primary goal of newborn mass screening (MS) for congenital adrenal hyperplasia (CAH) is the prevention of life-threatening salt-wasting crisis in the most severe forms of CAH, and MS for CAH has been implemented in several countries. We summarize here our experience and results from newborn CAH MS from 1982 to 2010 in Sapporo City. During these 28 yr, the level of 17-hydroxyprogesterone (17-OHP) was determined in MS of samples from 498,147 newborns. During this period, 26 individuals (19 females and 7 males) with 21-hydroxylase deficiency (21-OHD) were detected. Of the 26 CAH, 20 were classified as having the salt-wasting (SW) form, 4 were classified as having the simple virilizing (SV) form, and 2 were classified as having the noncalssic (NC) form. Therefore, the frequency of the classical type of CAH was 1 in 20,756. In order to improve the effectiveness, we employed high-performance liquid chromatography (HPLC) as a second tier test from 2000. During this period, among the recalled babies, 75.4% were born prior to the 37th wk of gestation age, and the recall rate was 5.38% for premature neonates and 0.06% for mature neonates. MS for CAH in Sapporo is effective for the identification of the SW and SV forms of 21-OHD. However, the recall rate of premature babies is still high after the introduction of HPLC as a second tier test.

In Sapporo, Japan, a neonatal screening program for congenital hypothyroidism (CH) has employed measurement of free thyroxine (T4) and TSH in the same filter-paper blood spot. This system has enabled us to identify primary CH and central CH during the neonatal period. The aim of this study was to clarify the prevalence and clinical characteristics of central CH. For this purpose, the screening program requested serum from infants with free T4 concentrations below the cut off value regardless of the TSH levels. Between January 2000 and December 2004, 83,232 newborns were screened and six central CH patients were detected as a result of follow-up of low free T4 and non-elevated TSH screening (1:13,872). This frequency is higher than in other studies. Four patients showed multiple pituitary hormone deficiency with pituitary malformations on magnetic resonance imaging. One patient was diagnosed as having Prader-Willie syndrome. The remaining patient was considered to have isolated central CH. Our study demonstrated that the frequency of central CH is 1:13,872. Free T4 measurement would also be advantageous in early recognition of multiple pituitary hormone deficiency.

ABSTRACT:In Sapporo city of Japan, neonatal screening for congenital hypothyroidism has used the measurement of free thyroxine (T4) and thyroid-stimulating hormone (TSH) in the filter-paper blood spot. This system has enabled us to identify hyperthyroxinemic diseases. Filter papers were collected from neonatal infants born at 4 -6 d of age and neonates who showed elevated free T4 (Ͼ4.0 ng/dL, 4 SD above the mean) were studied. Between January 2000 and December 2006, 83,232 newborns were screened. Eleven infants demonstrated persistent hyperthyroxinemia. One patient with slightly elevated free T4 and normal TSH was diagnosed as having familial dysalbuminemic hyperthyroxinemia (FDH). The other two patients with elevated free T4 without suppressed TSH were considered as having resistance of thyroid hormone (RTH), and analysis of thyroid hormone receptor (TR) ␤ gene confirmed the diagnosis. The remaining eight patients were diagnosed as having neonatal Graves' disease (NGD). Seven of eight pregnant women were treated with antithyroid drug and thus only one unrecognized NGD during pregnancy was detected by screening. Our screening system enables for early awareness of RTH and FDH. Regarding Graves' disease, the benefit of elevated free T4 screening is small, because most pregnant women with Graves' disease were managed. (Pediatr Res 66: 312-316, 2009) C ongenital hypothyroidism is the most prevalent endocrine disorder in the newborn, with a rather constant worldwide incidence of permanent congenital hypothyroidism of 1:3000 to 1:4000 newborns (1,2). The main purpose of neonatal mass screening for congenital hypothyroidism is early detection and treatment to hypothyroidism. During the past three decades, this screening has been very successful with the vast majority of patients with congenital hypothyroidism achieving normal neurologic outcome (1-3). Two methods for the screening system are now used. Most screening programs in Europe and Asia, including Japan, use primary thyroidstimulating hormone (TSH) screening. Another program is thyroxine (T4) or free T4-based neonatal screening (4 -6). T4 or free T4 screening enables the detection of hyperthyroxinemia in addition to congenital hypothyroidism. In hyperthyroxinemic disorders, neonatal Graves' disease (NGD) is thought to be the most prevalent and the occurrence is estimated as one in 10,000 to 50,000 newborn infants (7-9). Activating mutation of TSH receptor mutations and gain of function mutations of Gs␣ protein McCnune-Albright syndrome has been also reported to cause hyperthyroidism in neonatal period (10,11). LaFranchi et al. (12) have reported the first systematic study to screen neonatal hyperthyroxinemia using T4 screening in Oregon. According to their study, any case with NGD among 80,884 infants was not detected. Instead, 10 had thyroxinebinding globulin excess, five were thought to be familial dysalbuminemic hyperthyroxinemia (FDH), and two had resistance of thyroid hormone (RTH). After this report, the study of differential diagnosis of neonatal hyperth...

These findings suggest that maternal exposure to OH-PCBs during pregnancy may increase both maternal and neonatal FT4 levels. Neonatal FT4 is presumed to be increased by prenatal 4-OH-CB187 indirectly, and this process may be mediated by maternal THs and neonatal TSH.

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