Prenatal dexamethasone treatment in pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: effect on midgestational amniotic fluid steroid levels.
Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency by amniotic fluid (AF) steroid analysis is not possible in those cases in which prenatal dexamethasone (DEX) therapy is initiated to prevent virilization of female CAH fetuses because AF steroid levels are suppressed if DEX therapy is continued beyond amniocentesis (AC). In order to use AF steroids for prenatal diagnosis, it is necessary to discontinue DEX therapy for 5 days before AC. To study the effects of this interruption on AF steroid levels, we measured levels of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone (170HP), 11-deoxycortisol, cortisol, and cortisone as well as androstenedione (delta 4-A) in AF samples (16-18 weeks) obtained from 25 pregnancies at risk for CAH treated with Dex (daily dosage: 1.0-1.5 mg). The prenatal diagnosis of 14 normal fetuses and 11 affected CAH fetuses was postnatally confirmed in all cases. Additionally, steroid levels were measured in AF samples (16-18 weeks) from 8 untreated CAH fetuses and in 19 AF samples (weeks 16-20) obtained in normal pregnancies. In 17/19 prenatally diagnosed CAH fetuses, the affected sibs had the salt wasting (SW)-form, in 2 cases the simple virilizing (SV)-form. All steroids were measured by RIA after extraction and Sephadex LH-20 chromatography. AF levels of aldosterone, corticosterone, deoxycorticosterone, progesterone, cortisol, cortisone, and 11-deoxycortisol were not different between CAH fetuses, prenatally DEX-treated normal fetuses and untreated controls. The 170HP-levels of the CAH-SW-fetuses (range: 19.9-59.8 mmol/L) were clearly above the normal range (3.74-11.6), but normal in the SV-fetuses (10.9, 11.5), whereas delta-4 A-levels (normal range: 0.87-5.13 mmol/L) were elevated both in the SW-(range: 6.53-37.6) and the SV-form (9.37,6.25) of CAH. 170HP and delta-4 A levels of prenatally DEX-treated pregnancies with normal fetuses were not different from levels found in normal pregnancies. Mean 170HP and delta-4 A AF steroid levels of prenatally DEX-treated CAH-pregnancies were slightly lower (NS) than levels of untreated CAH-pregnancies (170HP: 30.5 vs. 40.7; delta-4 A: 15.8 vs. 21.1). 170HP levels are elevated in the SW-form of CAH, but not in the SV-form. However, with the combination of 170HP and delta-4 A levels it is possible to diagnose prenatally both forms. There is no rebound phenomenon of AF steroid levels if DEX therapy is interrupted 5 days before amniocentesis.
Dörr
H G
HG
Department of Pediatrics, Universities of Erlangen-Nürnberg, Germany.
Sippell
W G
WG
D019326:17-alpha-Hydroxyprogesterone; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000517:prevention & control*; D000450:Aldosterone / Q000032:analysis / Q000378:metabolism; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D000735:Androstenedione / Q000032:analysis / Q000378:metabolism; D003345:Corticosterone / Q000032:analysis / Q000378:metabolism; D003348:Cortisone / Q000032:analysis / Q000378:metabolism; D003350:Cortodoxone / Q000032:analysis / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism; D006908:Hydroxyprogesterones / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D012307:Risk Factors; D013256:Steroids / Q000032:analysis / Q000378:metabolism*
D006908:Hydroxyprogesterones; D013256:Steroids; D000735:Androstenedione; D000450:Aldosterone; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D003348:Cortisone; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone