Congenital Hypopituitarism as a Cause of Undetectable Estriol Levels in the Maternal Triple-Marker Screen

Marshall, Ian; Ugrasbul, Figen; Manginello, Frank P.; Wajnrajch, Michael; Shackleton, Cedric; New, Maria I.; Vogiatzi, M V

doi:10.1210/jc.2003-030495

Cited by 18 publications

(13 citation statements)

References 32 publications

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“…Although these entities are associated with XY gender reversal, our case was a female and there were no abnormal findings of the genitalia upon prenatal and postnatal examination. Other possibilities include X-linked congenital adrenal hypoplasia, resistance to ACTH, and secondary adrenal insufficiency, either isolated or as part of multiple pituitary hormone deficiency 15-17. Our observation of extremely low estriol levels during pregnancy as a predictor of CLAH suggests that each case of extremely low estriol detected by the maternal screening test should be reevaluated.…”

Section: Discussionmentioning

confidence: 89%

Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings

Lee

Chae

et al. 2011

Yonsei Med J

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Congenital lipoid adrenal hyperplasia (CLAH) is caused by mutations to the steroidogenic acute regulatory protein (StAR) gene associated with the inability to synthesize all adrenal and gonadal steroids. Inadequate treatment in an infant with this condition may result in sudden death from an adrenal crisis. We report a case in which CLAH developed in Korean siblings; the second child was prenatally diagnosed because the first child was affected and low maternal serum estriol was detected in a prenatal screening test. To our knowledge, this is the first prenatal diagnosis of the Q258X StAR mutation, which is the only consistent genetic cluster identified to date in Japanese and Korean populations.

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Section: Discussionmentioning

confidence: 89%

Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings

Lee

Chae

et al. 2011

Yonsei Med J

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“…Low maternal estriol in pregnancy is known to be associated with fetal hypopituitarism with ACTH deficiency (10), but we did not check maternal serum and urinary estriol levels as well as fetal pituitary hormones. Although the remote possibility of septo-optic dysplasia remains to be left, well developed optic chiasma and optic nerves without associated brain anomalies favor isolated septal agenesis in the present cases.…”

Section: Discussionmentioning

confidence: 99%

Absence of the Septum Pellucidum Associated with a Midline Fornical Nodule and Ventriculomegaly: A Report of Two Cases

et al. 2010

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We report two autopsy cases that revealed the partial absence of the septum pellucidum with ventriculomegaly. In each case, the brain showed mild dilatation of both frontal horns of the lateral ventricles, normal third and fourth ventricles and no aqueductal stenosis. The posterior portion of the septum pellucidum was absent and the fornices were fused in a single midline nodule, abnormally displaced to a caudal position and lodged in the foramina of Monro. The brain base showed no apparent abnormalities; the optic nerves were well developed. We conclude that the caudally displaced fornix in the absence of the septum pellucidum may have intermittently obstructed the foramina of Monro and induced mild ventriculomegaly.

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“…We attempt diagnosis of low-estriol conditions by GC/MS analysis of maternal urinary steroids with the rationale that this medium contains metabolites of all steroids that are synthesized in the fetus. Using this technology, we have described the diagnosis of steroid sulfatase deficiency (STS) [Glass et al, 1998], fetal adrenal hypoplasia [Marshall et al, 2003], and 7-dehydrosterol-7-reductase deficiency (DHCR7 deficiency, the Smith-LemliOpitz syndrome) [Shackleton et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): A disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley–Bixler syndrome phenotype

Shackleton¹,

Marcos²,

Arlt

et al. 2004

American J of Med Genetics Pt A

100

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We report studies on the second pregnancy of a woman who had previously given birth to a virilized female infant. The cause of the virilization had not been established, but common forms of congenital adrenal hyperplasia (CAH) were excluded. Longitudinal monitoring of the second pregnancy revealed that estriol excretion failed to increase normally, reaching a maximum 0.7 mg/24 hr at the end of pregnancy (normal mean 30 mg/24 hr). The mother showed signs of virilization by the 23rd week of gestation and aromatase deficiency was suspected. However, predicted urinary metabolites for diagnosis of aromatase deficiency (for example, 16alpha-hydroxyandrosterone) were not increased significantly during the pregnancy. Interestingly, excretion of the androgen metabolite androsterone increased rapidly at the beginning of pregnancy and peaked around the 20th week, suggesting increased production of testosterone and 5alphaDHT, probably the cause of maternal virilization. Urine steroid analysis by GC/MS showed gradually increasing excretion (9 mg/24 hr) of the normally minor metabolite 5alpha-pregnane-3beta,20alpha-diol (epiallopregnanediol), an epimer of the dominant progesterone metabolite pregnanediol (5beta-pregnane-3alpha,20alpha-diol). We believe epiallopregnanediol is largely the maternal urinary excretion product of fetal 5-pregnene-3beta,20alpha-diol, the principal metabolite of pregnenolone, implying a build-up of the latter steroid in the fetal adrenal. These findings suggested that the 'block' in the estriol biosynthetic pathway occurs at an early stage with 17-hydroxylation of pregnenolone being affected. The male baby born of this pregnancy had normal genitalia but showed a urinary steroid profile indicating partial deficiencies of P450c17 and P450c21. However, no mutations in the corresponding CYP17 and CYP21 genes were identified. Urinary steroid analysis carried out on his virilized older sibling showed the same pattern of metabolites. Recently, we determined that this disorder is caused by mutations in P450 oxidoreductase (OR), the essential redox partner for CYP17 and CYP21 hydroxylases. The novel metabolic profile has now been seen in many patients, most diagnosed with the skeletal dysplasia Antley-Bixler syndrome. We propose that excessive excretion of epiallopregnanediol together with low estriol may be prenatally diagnostic for OR deficiency (ORD).

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Congenital Hypopituitarism as a Cause of Undetectable Estriol Levels in the Maternal Triple-Marker Screen

Cited by 18 publications

References 32 publications

Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings

Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings

Absence of the Septum Pellucidum Associated with a Midline Fornical Nodule and Ventriculomegaly: A Report of Two Cases

Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): A disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley–Bixler syndrome phenotype

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