[Reevaluation of recalled infants by neonatal mass screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Diagnostic value of pregnanetriolone in a single urine specimen using glass capillary gas chromatography]

Abstract

To establish a detailed reevaluation system for infants who were recalled by a neonatal mass screening for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, pregnanetriol (PT) and pregnanetriolone (PTL) in a single urine specimen combined with plasma 17 alpha-hydroxyprogesterone (17-OHP) and 21-deoxycortisol (21-DOF) were determined by a simple method using glass capillary gas chromatography. A pilot study of neonatal mass screening for CAH with a determination of "disc 17-OHP" value in dried blood on filter paper was carried out in Western Shizuoka Prefecture. During the study period (32 months), 37472 neonates were determined by mass screening, and 362 neonates proved to be abnormal candidates who needed further evaluations. From out of these candidates, 262 neonates responded with recall and were studied. Amongst these 262 neonates, 241 neonates visited directly our outpatient clinic at Hamamatsu University Hospital. The reevaluation conducted at our clinic included a physical examination, detailed family history, measurement of serum electrolytes, disc 17-OHP, plasma 17-OHP and 21-DOF values, and PT and PTL in a single urine specimen. Consequently, 3 neonates appeared to be patients with CAH. Two of them were the salt-losing type and the other was the simple virilizing type. The rest of the candidates who received reevaluation were finally decided to be healthy neonates, indicating false positivity by mass screening. Compared to the candidates who showed false positivity in the mass screening, the CAH patients had an apparently high urinary PT and PTL titer of ten or one hundred fold. Additionally, despite corticosteroid treatment in one case, significantly elevated levels of PT and PTL were detected. To assay PTL was a more reliable parameter for the detection of CAH and for following up the candidates because PTL was not detectable in 63.3% of the false positive cases, suggesting that PTL was less likely to indicate false positive cases. PTL was detected at more than 0.01 microgram/ml urine in 19.4% of false positive cases, however, no case showed further elevation of PTL during the follow up period. In all false positive cases, PTL was not detectable until the age of six months. Despite problems to be resolved, determination of urinary PTL titer is valuable for the detection of CAH patients. In addition, urinary PTL could be a good parameter for the further follow up of false positive cases in neonatal mass screening.