Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia

Abstract

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 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. Conclusion: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.

Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia

“…These infants should be followed up until there is a definite diagnosis or normalization of serum 17OHP levels, as these situations add not only to the cost of screening programs, but can also be the cause of great anxiety to parents. In order to minimize these problems, cutoff values for 17OHP were established for NBS according to birthweight or gestational age (11)(12)(13)(14).…”

Problems of neonatal screening on congenital adrenal hyperplasia

“…Öå ïîÿñíþºòüñÿ çíèaeåííÿì àêòèâíîñò³ äåê³ëüêîõ ôåðìåíò³â ñòåðî¿äî´åíåçó, íàäòî íà 29-ìó òèaeí³ âàã³òíîñò³. ²ñíóº íåãàòèâíà êîðåëÿö³ÿ ì³ae ãåñòàö³éíèì â³êîì äèòèíè, éîãî ìàñîþ ò³ëà òà ð³âíåì 17-ÎÍÐ [16,20,26,27,31,40,43]. Òîìó á³ëüø³ñòü ñêðèí³íãîâèõ ïðîãðàì ìàþòü ð³çí³ íîðìàòèâí³ ïîêàçíèêè 17-ÎÍÐ çà-ëåaeíî â³ä ìàñè ò³ëà íîâîíàðîäaeåíèõ òà ¿õ ãåñ-òàö³éíîãî â³êó, ùî äîçâîëÿº çá³ëüøèòè ïîçèòèâíó ïðîãíîñòè÷íó ö³íí³ñòü ñêðèí³íãó.…”

“…ijòè ïåðøî¿ ãðóïè ó ïðîöåñ³ ñïî-ñòåðåaeåííÿ çàëèøàþòüñÿ çäîðîâèìè áåç êë³í³÷-íèõ ³ ëàáîðàòîðíèõ îçíàê ÂÃÊÍÇ àáî ìàþòü ÒÄÊÍÇ ³ç ïåðñèñòåíö³ºþ ï³äâèùåíîãî ð³âíÿ 17-ÎÍÐ äî 3-6 ì³ñÿö³â â³ä íàðîäaeåííÿ. P. Cavarzere et al [20] ï³ñëÿ ïðîâåäåííÿ ãåíåòè÷íîãî àíàë³çó â ãðóï³ îáñòåaeåíèõ ³ç ÒÄÊÍÇ íå çàðåºñ-òðóâàëè aeîäíîãî äåôåêòó ãåíà CYP21, àëå ö³ äàí³ âèìàãàþòü ïîäàëüøîãî âèâ÷åííÿ. Äëÿ ä³òåé äðó-ãî¿ ãðóïè ³ñíóº éìîâ³ðí³ñòü ðîçâèòêó â³ðèëüíî¿ ôîðìè.…”

“…Íà ÷àñ âñòàíîâëåííÿ ä³àãíîçó ö³ ïàö³ºí-òè ìàþòü îòðèìóâàòè ë³êóâàííÿ ãëþêîêîðòèêî¿-äàìè çã³äíî ç ïðîòîêîëîì [8]. Äî òðåòüî¿ ãðóïè âõîäÿòü ä³òè, ó ÿêèõ ìîaeëèâèé ðîçâèòîê ï³çíüî¿ íåêëàñè÷íî¿ ôîðì³ ÂÃÊÍÇ ³ ÿê³ ÷àñòî º íîñ³ÿìè ãîìîçèãîòíî¿ ìóòàö³¿ V281L òà ³íîä³ ìîaeóòü ìàòè ãåòåðîçèãîòí³ ìóòàö³¿ ãåíà CYP21, îäíà ç ÿêèõ ïðèòàìàííà íåêëàñè÷í³é ôîðì³ ÂÃÊÍÇ, ³íøà -êëàñè÷í³é ôîðì³ õâîðîáè, ùî îáóìîâëþº íåçíà÷-íå çá³ëüøåííÿ ð³âíÿ 17-ÎÍÐ ï³ä ÷àñ ñêðèí³íãó [5,9,20,23,45]. ²íøà ïðîáëåìà, ùî âèíèêຠï³ä ÷àñ ïðîâå-äåííÿ ñêðèí³íãó, öå õèáíî-íåãàòèâí³ ïîêàçíèêè 7-ÎÍÐ.…”

“…Çã³äíî ç äàíèìè ë³-òåðàòóðè, ï³äâèùåííÿ ð³âíÿ 17-ÎÍÐ ï³ä ÷àñ ðå-òåñòóâàííÿ òðàïëÿºòüñÿ ëèøå ó ä³òåé ³ç ÂÃÊÍÇ. Ïðîòå ï³ñëÿ ðå-òåñòóâàííÿ çàëèøàþòüñÿ â³ä 1% äî 8% ä³òåé, ó ÿêèõ ð³âåíü 17-ÎÍÐ íåäîñòàòíüî çíèaeóºòüñÿ ³ ÿê³ ïîòðåáóþòü ïîäàëüøîãî ñïî-ñòåðåaeåííÿ [5,20,40].…”