Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000-2004): It's Prevalence and Clinical Characteristics

Abstract

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.

Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper

“…The latter category of CH cases is termed as CH of central origin (CH-C). The incidence of CH-C is estimated to be w1 in 20 000-30 000 live births (3,5,6,7,10), which is much higher than previously thought. Nevertheless, CH screening in Japan is mainly based on the detection of elevated TSH levels in dried blood samples on filter paper (primary TSH strategy).…”

“…Most of the screening centers adopt a primary TSH and backup FT 4 system: the filter paper method is used for measuring TSH in all newborns, while it is used for measuring FT 4 only in those with high TSH values for confirmation of possible hypothyroidism (11,12). To detect CH-C, certain areas, including Kanagawa prefecture and Sapporo city, have adopted a combined primary TSH-FT 4 screening system (7,9). After the report from Sapporo city (7), this report is the second audit of this CH-C newborn screening system, conducted on a larger population and for a longer study period.…”

“…A Dutch screening system with TSH, T 4 , and TBG determination (5) reported a prevalence rate of 22% of isolated CH-C, which is closer to our findings. Secondly, ethnic differences may be a factor: in Sapporo city, two of six CH-C patients were reported to demonstrate isolated hypothyroidism (7). Thirdly, some patients may not have been correctly diagnosed: a patient (patient 21 in Table 2) with pituitary hypoplasia is likely to have other hormone deficiencies.…”

“…While most CH cases are due to CH of thyroidal origin (CH-T) manifesting as thyroid dysgenesis or thyroid hormone synthesis defects, a significant number of CH cases are due to inadequate thyroid-stimulating hormone (TSH) secretion from the anterior pituitary (3,4,5,6,7,8,9). The latter category of CH cases is termed as CH of central origin (CH-C).…”

“…Sapporo city has also adopted the same screening system. The report of a 5-year audit in Sapporo city was released in 2004, in which six CH-C cases were identified through this screening (7). However, the study in Sapporo included only patients showing positive screening results, which preclude evaluation of the sensitivity of screening in detecting CH-C.…”