Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia.
OBJECTIVE
Neonatal screening for congenital adrenal hyperplasia (CAH) is characterized by a high false-positive rate, mainly among preterm and low birth weight infants. The aims of this study were to describe a subgroup of infants with transient serum hyper-17-hydroxyprogesteronemia (hyper-17-OHPemia) and to compare them with false positive and affected by 21-hydroxylase deficiency newborns.


METHODS
We retrospectively analyzed the clinical data of all newborns positive at CAH neonatal screening, who were referred to our hospital to confirm the diagnosis from 2002 to 2006. They were submitted to clinical investigations and blood tests to evaluate 17-hydroxyprogesterone (17-OHP), renin, and electrolyte levels. CAH-unaffected newborns with increased serum 17-OHP were submitted to strict follow-up monitoring, which included an ACTH-stimulating test and genetic analysis of the 21-hydroxylase gene, until serum 17-OHP decreased.


RESULTS
Thirty-seven newborns with gestational ages ranging from 33 to 40 weeks were studied. Eight infants (three male and five female) were affected by CAH (serum 17-OHP: 277.5 (210-921) nmol/l), 14 (ten male and four female) were false positives (17-OHP: 3.75 (0.3-8.4) nmol/l), and 15 (ten male and five female) showed a serum hyper-17-OHPemia (17-OHP: 15.9 (9.9-33) nmol/l). No mutations of the 21-hydroxylase gene were found in infants with hyper-17-OHPemia and their serum 17-OHP levels were normalized by the third month of life.


CONCLUSIONS
We identified a population of infants with transient serum hyper-17-OHPemia, and no clinical signs of disease or 21-hydroxylase gene mutations. No further investigations are necessary after birth in these newborns if 17-OHP levels decrease, other confirmatory tests such as ACTH-stimulation test or genotyping analysis are necessary only if symptoms appear.
Cavarzere
Paolo
P
Pediatric Endocrinology Unit, INSERM U845, Hôpital Necker-Enfants Malades, Paris Descartes University, 75748 Paris, France. paolocavarzere@yahoo.it
Samara-Boustani
Dinane
D
Flechtner
Isabelle
I
Dechaux
Michèle
M
Elie
Caroline
C
Tardy
Véronique
V
Morel
Yves
Y
Polak
Michel
M
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D004247:DNA / Q000235:genetics; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004573:Electrolytes / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D012083:Renin / Q000097:blood; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013739:Testosterone / Q000097:blood
D004573:Electrolytes; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D013255:Steroid 21-Hydroxylase; D012083:Renin; D006854:Hydrocortisone