Late-Onset 21-Hydroxylase Deficiency Is an Allelic Variant of Congenital Adrenal Hyperplasia Characterized by Attenuated Clinical Expression and Different HLA Haplotype Associations

Gp, Chrousos; Dl, Loriaux; Mann, Dean L.; Gb, Cutler

doi:10.1159/000179502

Cited by 38 publications

(8 citation statements)

References 27 publications

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“…Retrospective analysis of the etiologies of hirsutism and oligomenorrhea revealed that 16 of 108 (14%) of young women presenting to this institution for endocrinologic evaluation of these complaints had nonclassic 21‐hydroxylase deficiency 54. In other published series the prevalence of nonclassic 21‐hydroxylase deficiency in hirsute, oligomenorrheic women ranges from 1.2% to 30% 55–59. The disparity in frequency of nonclassic 21‐hydroxylase deficiency reported by different authors may be attributed to differences in the ethnic groups studied because the disease frequency is ethnic specific (Table 3).…”

Section: Clinical Forms Of Adrenal Hyperplasia Caused By 21‐hydromentioning

confidence: 93%

“…54 In other published series the prevalence of nonclassic 21hydroxylase deficiency in hirsute, oligomenorrheic women ranges from 1.2% to 30%. [55][56][57][58][59] The disparity in frequency of nonclassic 21-hydroxylase deficiency reported by different authors may be attributed to differences in the ethnic groups studied because the disease frequency is ethnic specific (TABLE 3).…”

Section: B Nonclassic 21-hydroxylase Deficiencymentioning

confidence: 99%

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An Update of Congenital Adrenal Hyperplasia

New

2004

Annals of the New York Academy of Sciences

149

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Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations that encode for enzymes involved in one of the various steps of adrenal steroid synthesis. These defects result in the absence or the decreased synthesis of cortisol from its cholesterol precursor. The anterior pituitary secretes excess adrenocorticotrophic hormone (ACTH) via feedback regulation by cortisol, which results in overstimulation of the adrenals and causes hyperplasia. Symptoms due to CAH can vary from mild to severe depending on the degree of ensymatic defect. In the classical form of CAH, there is a severe enzymatic defect owing to mutations in the CYP21 gene. Classically affected female fetuses undergo virilization of the genitalia prenatally and present with genital ambiguity at birth; however, prenatal treatment of CAH with dexamethasone to prevent ambiguity has been successfully utilized for over a decade. In the less severe, late-onset form of CAH, prenatal virilization does not occur. The milder enzyme deficiency was termed nonclassical 21-hydroxylase deficiency (NC21OHD) in 1979 and was later found to be the most common autosomal recessive disorder in humans. Disease frequency of NC21OHD varies between ethnic groups with the highest ethnic-specific disease frequency in Ashkenazi Jews at 1/27. NC21OHD is diagnosed by serum elevations of 17-OHP that plot on a nomogram between the range for unaffected individuals and levels observed for classical CAH and is typically confirmed with molecular genetic analysis. Similar to classical CAH, nonclassical 21-hydroxylase deficiency may cause premature development of pubic hair, advanced bone age, accelerated linear growth velocity and diminished final height in both males and females. Severe cystic acne has also been attributed to nonclassical CAH. Women may present with symptoms of androgen excess, including hirsutism, temporal baldness, and infertility. Menarche in females may be normal or delayed and secondary amenorrhea is a frequent occurrence. Polycystic ovary syndrome may also be seen in these patients. In males, early beard growth, acne, and growth spurt may prompt the diagnosis of NC21OHD. Although many males appear to be asymptomatic, they may present with oligozoospermia or diminished fertility. Individuals presenting to dermatology and infertility clinics with symptoms of hyperandrogenemia are rarely screened for NC21OHD. However, with hormonal and molecular genetic screening, previously undiagnosed patients may be identified and can therefore receive glucocorticoid treatment, which has been shown to reverse symptoms within 3 months.

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Section: Clinical Forms Of Adrenal Hyperplasia Caused By 21‐hydromentioning

confidence: 93%

Section: B Nonclassic 21-hydroxylase Deficiencymentioning

confidence: 99%

An Update of Congenital Adrenal Hyperplasia

New

2004

Annals of the New York Academy of Sciences

149

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“…In fact, CAH as a result of 21-OH deficiency is the most common cause of ambiguous genitalia in newborn genetic females ( fig. [18,19] Patients with nonclassic CAH may present with early pubarche, or as an adolescent or young adult female with hirsutism, oligo-amenorrhoea or infertility [ fig. The age at diagnosis in males varies according to the severity of mineralocorticoid deficiency.…”

Section: Clinical Featuresmentioning

confidence: 99%

Congenital Adrenal Hyperplasia

Merke

Kabbani

2001

Paediatric Drugs

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Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a common disorder, and is characterised by a defect in cortisol biosynthesis with or without a defect in aldosterone synthesis and androgen excess. The classic form, also known as the severe form, occurs in 1:15,000 births worldwide, while the nonclassic or mild form occurs in approximately 1:1,000 births worldwide and is much more common (up to 1:20) in certain ethnic groups. In classic 21-hydroxylase deficiency, glucocorticoids are given in doses sufficient to suppress adrenal androgen secretion, and mineralocorticoids are given to normalise electrolytes and plasma renin activity. The management of CAH may be complicated by iatrogenic Cushing's syndrome, inadequately treated hyperandrogenism, or both. Prenatal treatment may decrease virilisation of the affected female foetus, but the efficacy and safety of treating CAH prenatally remains to be fully defined. Close clinical monitoring of growth and development is essential to optimise treatment outcome. New treatment approaches are currently under investigation in the most severely affected patients, while nonclassic CAH does not always require treatment.

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“…Late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) deficiency has been estab lished as an allelic variant of classical congenital adrenal hyperplasia (CAH) on the basis of hormonal and HLA linkage studies [1][2][3], Unlike classical CAH, which presents at birth with virilization, LOCAH may become partial 11 (3-hydroxylase (1 l(3-0H)and 3|3-hydroxysteroid dehydrogenase deficiencies [8], as well as mild defects in 21-OH.…”

Section: Introductionmentioning

confidence: 99%

Usefulness of an ACTH Test in the Diagnosis of Nonclassical 21-Hydroxylase Deficiency among Children Presenting with Premature Pubarche

Ibáñez¹,

Bonnin

Zampolli

et al. 1995

Horm Res

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Adrenal steroidogenic function was evaluated in 55 children with typical premature pubarche (PP) to investigate the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) deficiency and to evaluate the usefulness of routine ACTH testing in these patients. Four patients fulfilled criteria for LOCAH due to 21-OH deficiency. Of these, 3 had elevated baseline 17-OHP levels; in the remainder, basal 17-OHP was within normal limits. Mean basal and stimulated 17-OHP responses in children with PP, excluding those with an enzymatic defect, were very similar to those of controls (2.3 ± 1.8 vs. 1.6 ± 0.9 and 10.0 ± 4.0 vs. 9.5 ± 3.3 nmol/l, respectively). However, 5 patients had basal 17-OHP values exceeding the upper limit of controls and 8 patients, including 2 of those with elevated baseline levels, showed supranormal poststimulated 17-OHP values. Body mass indices, height standard deviation scores (SDS) and bone age SDS showed no correlation with the basal or incremental rises of any hormone. Four (7%) of our population of patients with typical PP had LOCAH due to 21-OH deficiency. Basal 17-OHP levels were helpful in detecting altered steroidogenesis in 3, thus suggesting that in some PP patients, LOCAH due to this enzymatic defect may remain undiagnosed if ACTH stimulation test is not routinely performed.

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Late-Onset 21-Hydroxylase Deficiency Is an Allelic Variant of Congenital Adrenal Hyperplasia Characterized by Attenuated Clinical Expression and Different HLA Haplotype Associations

Cited by 38 publications

References 27 publications

An Update of Congenital Adrenal Hyperplasia

An Update of Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia

Usefulness of an ACTH Test in the Diagnosis of Nonclassical 21-Hydroxylase Deficiency among Children Presenting with Premature Pubarche

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