Abstract
Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot be converted to pregnenolone. As a result, affected individuals can make no steroid hormones, so that all affected newborns are phenotypic females, irrespective of karyotype. We studied two pregnancies in a family with two previously affected children by examining fetal karyotype, genital ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH tests on family members. Prenatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 α-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and estriol were either extremely low or undetectable, suggesting that these detected steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother’s circulation. Absent fetal steroidogenesis was confirmed by gas chromatography and mass spectrometry of both fetal and maternal serum. The responses of 10 different steroids to adrenal stimulation with ACTH in the obligately heterozygous parents were normal. Thus, unlike the case with other forms of CAH, heterozygosity cannot be determined by hormonal responses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc protein, confirming that P450scc is intact in these patients.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 200-205 |
| Number of pages | 6 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 80 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 1995 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
Cite this
Prenatal diagnosis of congenital lipoid adrenal hyperplasia. / Saenger, Paul; Klonari, Zoi; Black, Stephen Matthew; Abram, Cyril A.L.; Compagnone, Nathalie; Mellon, Synthia H.; Black, Stephen M.; Miller, Walter L.; Shackelton, Cedric H.L.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 1, 01.01.1995, p. 200-205.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prenatal diagnosis of congenital lipoid adrenal hyperplasia
AU - Saenger, Paul
AU - Klonari, Zoi
AU - Black, Stephen Matthew
AU - Abram, Cyril A.L.
AU - Compagnone, Nathalie
AU - Mellon, Synthia H.
AU - Black, Stephen M.
AU - Miller, Walter L.
AU - Shackelton, Cedric H.L.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot be converted to pregnenolone. As a result, affected individuals can make no steroid hormones, so that all affected newborns are phenotypic females, irrespective of karyotype. We studied two pregnancies in a family with two previously affected children by examining fetal karyotype, genital ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH tests on family members. Prenatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 α-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and estriol were either extremely low or undetectable, suggesting that these detected steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother’s circulation. Absent fetal steroidogenesis was confirmed by gas chromatography and mass spectrometry of both fetal and maternal serum. The responses of 10 different steroids to adrenal stimulation with ACTH in the obligately heterozygous parents were normal. Thus, unlike the case with other forms of CAH, heterozygosity cannot be determined by hormonal responses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc protein, confirming that P450scc is intact in these patients.
AB - Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot be converted to pregnenolone. As a result, affected individuals can make no steroid hormones, so that all affected newborns are phenotypic females, irrespective of karyotype. We studied two pregnancies in a family with two previously affected children by examining fetal karyotype, genital ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH tests on family members. Prenatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 α-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and estriol were either extremely low or undetectable, suggesting that these detected steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother’s circulation. Absent fetal steroidogenesis was confirmed by gas chromatography and mass spectrometry of both fetal and maternal serum. The responses of 10 different steroids to adrenal stimulation with ACTH in the obligately heterozygous parents were normal. Thus, unlike the case with other forms of CAH, heterozygosity cannot be determined by hormonal responses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc protein, confirming that P450scc is intact in these patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028851310&partnerID=8YFLogxK
U2 - 10.1210/jcem.80.1.7829612
DO - 10.1210/jcem.80.1.7829612
M3 - Article
C2 - 7829612
AN - SCOPUS:0028851310
VL - 80
SP - 200
EP - 205
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 1
ER -