Nonclassic Congenital Adrenal Hyperplasia

Witchel, Selma F.; Azziz, Ricardo

doi:10.1155/2010/625105

Cited by 68 publications

(53 citation statements)

References 74 publications

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“…Much is unknown about progesterone in CAH. However, high progesterone levels could contribute to female infertility 35 . In a case-control study of 16 women with classic CAH, those patients with a low LH pulse amplitude and frequency had higher progesterone levels and worse hormonal control than those with LH pulsatility similar to normal controls 36 .…”

Section: Discussionmentioning

confidence: 99%

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Debono

Mallappa

Gounden

et al. 2015

European Journal of Endocrinology

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Objectives The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing’s syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods Twenty-four hour serum sampling for corticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, dehydroepiandrosterone (DHEA), testosterone, progesterone and 24-hour urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration were calculated. Results A significant rhythm was confirmed for ACTH (r2 0.95;P<0.001), 17OHP (r2 0.70; P=0.003), androstenedione (r2 0.47;P=0.043), androsterone (r2 0.80;P<0.001), testosterone (r2 0.47;P=0.042) and progesterone (r2 0.64;P=0.006). The mean (SD) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone [4.3(2.3) and 9.7(3.5) hours], evening prednisone [4.5(2.0) and 10.3(2.4) hours], and daily dexamethasone [9.2(3.5) and 16.4(7.2) hours]. AUC0-24hr progesterone, androsterone and 24-hour urine pdiol were significantly related to 17OHP. Conclusion In CAH patients adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.

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Section: Discussionmentioning

confidence: 99%

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Debono

Mallappa

Gounden

et al. 2015

European Journal of Endocrinology

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“…Recombination events between CYP21A2 , the active gene, and a highly homologous pseudogene, CYP21A1P , account for most mutant alleles, with 10–12 mutations explaining the majority of affected alleles [9]. Classic salt-wasting CAH often is the result of a large gene deletion and a splicing mutation in the second intron, while there are few alleles that are specific to NCCAH [16].…”

Section: Geneticsmentioning

confidence: 99%

“…Mutations in CYP21A2 that are associated with classic CAH, both salt-wasting and simple virilizing, result in a 95–100% loss of enzymatic activity [10]. In the case of NCCAH, there is typically a 50–80% loss of enzyme activity [9]. …”

Section: Geneticsmentioning

confidence: 99%

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Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): An update

Trapp

Oberfield

2012

Steroids

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Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000–1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20–50% of 21-hydroxylase enzyme activity (vs. 0–5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000–1:2000 births (0.1–0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1–2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. and other alternatives, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome, and bone mineral density.

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“…Hyperinsulinemia, insulin resistance and polycystic ovarian morphology are frequently seen in patients with PCOS. However, it is important to note that an adverse metabolic profile is also frequently described in NCCAH and the presence of metabolic abnormalities or polycystic ovarian morphology does not exclude NCCAH [4].…”

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confidence: 99%

Nonclassic congenital adrenal hyperplasia and the heterozygote carrier

Ahmadi

Alvi

Urban³

2013

Expert Review of Endocrinology & Metabolism

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This article discusses the difficulty of differentiating three causes of adult androgen excess including nonclassic congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, polycystic ovarian syndrome and heterozygote carrier of CYP21 mutations based on clinical findings. It also reviews the screening modalities that discriminate patients with nonclassic congenital adrenal hyperplasia and the heterozygote carrier of CYP21 mutations from the normal population. In addition, the current management of hyperandrogenism and ovulatory dysfunction in these patients is described. Nonclassic congenital adrenal hyperplasia and the heterozygote carrier Expert Rev. Endocrinol. Metab. 8(3), 239-246 (2013) Keywords: 21-hydroxylase deficiency • diagnosis • heterozygote carrier • hyperandrogenism • nonclassic congenital adrenal hyperplasia • treatmentFor reprint orders, please contact reprints@expert-reviews.com

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Nonclassic Congenital Adrenal Hyperplasia

Cited by 68 publications

References 74 publications

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): An update

Nonclassic congenital adrenal hyperplasia and the heterozygote carrier

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