Prenatal Treatment in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Up-Date 88 of the French Multicentric Study

Forest, Maguelone G.; Bétuel, H; Dávid, M

doi:10.1080/07435808909039101

Cited by 163 publications

(57 citation statements)

References 39 publications

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“…6). As reported in previous studies (53)(54)(55), prenatally treated newborns did not differ significantly in birth weight from untreated newborns in our study. Mean birth weight was 3.4 kg for dexamethasone-treated fetuses and 3.5 kg (P ϭ 0.26) for controls.…”

Section: Biochemical Features Adrenal Steroidogenesis and Fetal Devesupporting

confidence: 89%

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

New

Wilson

1999

Proc. Natl. Acad. Sci. U.S.A.

147

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Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1͞27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre-and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11␤-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension.

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Section: Biochemical Features Adrenal Steroidogenesis and Fetal Devesupporting

confidence: 89%

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

New

Wilson

1999

Proc. Natl. Acad. Sci. U.S.A.

147

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“…Additionally, long term use of glucocorticoids has been advocated for prenatal therapy of fetuses at risk of congenital adrenal hyperplasia (Forest et al 1989, Carlson et al 1999. Experimental data suggests that exposure to glucocorticoids during development is associated with a risk of later metabolic and cardiovascular disorders.…”

Section: Figurementioning

confidence: 99%

Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids-fetal effect or maternal influence?

Nyirenda¹,

Welberg²,

Seckl³

2001

Journal of Endocrinology

142

127

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In a previous study, we showed that exposure of rats to dexamethasone (Dex) selectively in late pregnancy produces permanent induction of hepatic phosphoenolpyruvate carboxykinase (PEPCK) expression and hyperglycaemia in the adult offspring. The mechanisms by which glucocorticoids cause this programming are unclear but may involve direct actions on the fetus/neonate, or glucocorticoids may act indirectly by affecting maternal postnatal nursing behaviour. Using a cross-fostering paradigm, the present data demonstrate that switching the offspring at birth from Dex-treated dams to control dams does not prevent induction of PEPCK or hyperglycaemia. Similarly, offspring born to control dams but reared by Dex-treated dams from birth maintain normal glycaemic control. During the neonatal period, injection of saline per se was sufficient to cause exaggeration in adult offspring responses to an oral glucose load, with no additional effect from Dex. However, postnatal treatment with either saline or Dex did not alter hepatic PEPCK activity. Prenatal Dex permanently raised basal plasma corticosterone levels, but under stress conditions there were no differences in circulating corticosterone levels. Likewise, Dex-exposed rats had similar plasma catecholamine concentrations to control animals. These findings show that glucocorticoids programme hyperglycaemia through mechanisms that operate on the fetus or directly on the neonate, rather than via effects that alter maternal postnatal behaviour during the suckling period. The hyperglycaemic response does not appear to result from abnormal sympathoadrenal activity or hypothalamic-pituitary-adrenal response during stress.

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“…27 Dexamethasone, given antenatally to mothers who have children with congenital adrenal hyperplasia to prevent ambiguity of the genitalia, has been in use for a few years. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] The initial reports were rather discouraging, as the expected outcome of normal or near normal genitalia did not happen. 24 This was, however, most likely related to the fact that it was not used very early in pregnancy and the first trimester period was missed.…”

Section: Discussionmentioning

confidence: 99%

“…Using dexamethasone as early as possible, however, resulted in reducing the degree of virilization in at least two-thirds of reported cases. 18,21,23,28 The combination of a dedicated family and medical team is always needed for such a program. The medical team should include an obstetrician, radiologist, geneticist, biochemist, immunologist, nurses, pediatric surgeon, and a pediatrician or pediatric endocrinologist.…”

Section: Discussionmentioning

confidence: 99%

“…4 Advances in technology have made possible the prenatal diagnosis of CAH and subsequently, prenatal treatment with dexamethasone given to mothers throughout pregnancy and begun as early as possible has led to the prevention of virilization in at least three-fourths of affected infants. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In this article, prenatal dexamethasone therapy was given to a Saudi mother of children with CAH due to 21-hydroxylase deficiency. This has prevented ambiguity in the second daughter.…”

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confidence: 99%

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Prevention of Ambiguous Genitalia in Congenital Adrenal Hyperplasia

Herbish

1996

Ann Saudi Med

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Ambiguous genitalia is not an uncommon problem in Saudi Arabia. [1][2][3] Its most common cause is congenital adrenal hyperplasia (CAH) caused by any one of the three inborn errors of steroidogenesis; 21-hydroxylase (the most common), 11β-hydroxylase, and 36-hydroxysteroid dehydrogenase deficiency in genetic female babies. 4 Advances in technology have made possible the prenatal diagnosis of CAH and subsequently, prenatal treatment with dexamethasone given to mothers throughout pregnancy and begun as early as possible has led to the prevention of virilization in at least three-fourths of affected infants. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In this article, prenatal dexamethasone therapy was given to a Saudi mother of children with CAH due to 21-hydroxylase deficiency. This has prevented ambiguity in the second daughter. This is believed to be the first published local experience of this mode of prevention therapy. Case ReportA two-month-old male of a first-degree consanguineous couple presented with a history of recurrent vomiting and diarrhea and failure to thrive. He was found to have dehydration, hyponatremia, and hyperkalemia, and subsequently was diagnosed to have congenital adrenal hyperplasia due to 21-hydroxylase deficiency. He was therefore treated with hydrocortisone and 9-α -fluorocortisone. At the age of two years he was referred to the pediatric endocrine clinic at King Khalid University Hospital (KKUH), as per the wish of the family. Follow-up care was done and the parents were counseled.The mother then gave birth to her second infant, who has ambiguous genitalia ( Figure 1) and was immediately referred to KKUH for further management. She soon presented with hyponatremia and hyperkalemia. Appropriate replacement therapy was begun as explained above, with the addition of sodium chloride. Her chromosome analysis showed female karyotype (46,XX). Pelvic ultrasonography was not conclusive, but the genitogram showed female urethra. However, it had failed to visualize the uterus and the fallopian tubes. The 17-hydroxyprogesterone level was greater than 250 ng/mL (N = 0.21-1.4), androstendione level was 7.21 ng/mL (N=0.6-3.4), 11-deoxycorticosterone was 46.3 ng/mL (N=2.0-15), and renin >70 mg/mL/hr (N=0.68-1.38). Hormonal assay was performed in Bioscentia Laboratories (Germany). She then had clitoroplasty (clitoral recession) and vaginoplasty at one year of age, followed by vaginal dilatation at two and at three-and-one-half years of age.Despite some hesitation, after genetic counseling, the parents decided to have a third child. They were also informed at this stage about the preventive value of dexamethasone given to the mother during pregnancy and the very possible side effects which have been reported. At five weeks of gestation, the mother was placed on dexamethasone tablets 0.5 mg twice a day. At 16 weeks of gestation, she was subjected to amniocentesis, where the amniotic fluid chromosomal analysis showed 46,XY male karyotype. Dexamethasone was therefore disconti...

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Prenatal Treatment in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Up-Date 88 of the French Multicentric Study

Cited by 163 publications

References 39 publications

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

Steroid disorders in children: Congenital adrenal hyperplasia and apparent mineralocorticoid excess

Programming hyperglycaemia in the rat through prenatal exposure to glucocorticoids-fetal effect or maternal influence?

Prevention of Ambiguous Genitalia in Congenital Adrenal Hyperplasia

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