A Diagnosis Not to Be Missed: Nonclassic Steroid 11β-Hydroxylase Deficiency Presenting With Premature Adrenarche and Hirsutism

Reisch, Nicole; Högler, Wolfgang; Parajes, Silvia; Röse, I; Dhir, Vivek; Götzinger, Joachim; Arlt, Wiebke; Krone, Nils

doi:10.1210/jc.2013-1306

Cited by 62 publications

(63 citation statements)

References 24 publications

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“…The nonclassic form is extremely rare and presents with hyperandrogenism during childhood. 68 The CYP11B1 gene is located on chromosome 8q21, and consists of nine exons that are approximately 40kb from the highly homologous aldosterone synthase gene (CYP11B2). 69 Over 50 CYP11B1-inactivatig mutations that are distributed over the entire coding region exist, with the majority being missense and nonsense, but splice-site mutations, small deletions, small insertions, and complex rearrangements exist and result in absent or very little 11β-hydroxylase activity.…”

Section: β-Hydroxylase Deficiencymentioning

confidence: 99%

Genetics of Congenital Adrenal Hyperplasia

Hannah‐Shmouni

Chen²,

Merke

2017

Endocrinology and Metabolism Clinics of North America

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Section: β-Hydroxylase Deficiencymentioning

confidence: 99%

Genetics of Congenital Adrenal Hyperplasia

Hannah‐Shmouni

Chen²,

Merke

2017

Endocrinology and Metabolism Clinics of North America

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“…Other enzymatic defects causing LO-CAH with hyperandrogenism include mutations in the genes encoding for 3βHSD2 (HSD3B2) [41] and 11β-hydroxylase (P450c11, CYP11B1) [42]. ‘True' cortisone reductase deficiency, inactivating mutations in the 11β-hydroxysteroid dehydrogenase 1 (11βHSD1, HSD11B1) gene, and apparent cortisone reductase deficiency due to inactivating mutations in the hexose-6-phosphate dehydrogenase (H6PDH) gene, cause ACTH-driven adrenal hyperandrogenism by reduced peripheral conversion of cortisone to cortisol [43].…”

Section: Differential Diagnosis Of Pamentioning

confidence: 99%

Premature Adrenarche - A Common Condition with Variable Presentation

et al. 2015

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Adrenarche refers to a maturational increase in the secretion of adrenal androgen precursors, mainly dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). In premature adrenarche (PA), clinical signs of androgen action appear before the age of 8/9 years in girls/boys, concurrently with the circulating DHEA(S) concentrations above the usually low prepubertal level. The most pronounced sign of PA is the appearance of pubic/axillary hair, but also other signs of androgen effect (adult type body odor, acne/comedones, greasy hair, accelerated statural growth) are important to recognize. PA children are often overweight and taller than their peers, and the higher prevalence of PA in girls than in boys is probably explained by higher female adiposity and peripheral DHEA(S) conversion to active androgens. PA diagnosis requires exclusion of other causes of androgen excess: congenital adrenal hyperplasia, androgen-producing tumors, precocious puberty, and exogenous source of androgens. PA has been linked with unfavorable metabolic features including hyperinsulinism, dyslipidemia, and later-appearing ovarian hyperandrogenism. Although this common condition is usually benign, PA children with additional risk factors including obesity should be followed up, with the focus on weight and lifestyle. Long-term follow-up studies are warranted to clarify if the metabolic changes detected in PA children persist until adulthood.

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“…A urinary steroid profile (USP) shows characteristic high excretion of both 17-OHP and corticosterone metabolites. 47 Non-classic forms of CAH may also be attributable to mutations leading to mild defects in HSD3B2 48 and CYP11B1 [49][50][51] , POR 52 and StAR. 53 The interconversion of cortisol to cortisone can be defective in the reverse reaction by cortisone reductase (HSD11B1) and leads to a need for an increase in ACTH to raise cortisol and androgen production.…”

Section: Related Enzyme Defectsmentioning

confidence: 99%

“…A USP is not useful for NC-CAH, but may suggest other abnormalities in adrenal or ovarian function including tumours as a cause of virilisation. 17-OHP concentrations in the CYP21A1 heterozygote range can be seen basally or on ACTH stimulation in other forms of NC-CAH attributable to mutations with modest effects on HSD3B2 48 and CYP11B1 [49][50][51] and POR. 50,20 Further steroid measurements are needed as summarised in Table 2 or the USP will show abnormal patterns or ratios that are diagnostic.…”

Section: Hyperandrogenism In Adultsmentioning

confidence: 99%

17-Hydroxyprogesterone in children, adolescents and adults

Honour

2014

Ann Clin Biochem

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17-Hydroxyprogesterone (17-OHP) is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase. An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentrations of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotrophic hormone. The classical congenital adrenal hyperplasia (CAH) presents usually with virilisation of a girl at birth. Affected boys and girls can have renal salt loss within a few days if aldosterone production is also compromised. Diagnosis can be delayed in boys. A non-classical form of congenital adrenal hyperplasia (NC-CAH) presents later in life usually with androgen excess. Moderately raised or normal 17-OHP concentrations can be seen basally but, if normal and clinical suspicion is high, an ACTH stimulation test will show 17-OHP concentrations (typically >30 nmol/L) above the normal response. NC-CAH is more likely to be detected clinically in females and may be asymptomatic particularly in males until families are investigated. The prevalence of NC-CAH in women with androgen excess can be up to 9% according to ethnic background and genotype. Mutations in the 21-hydroxylase genes in NC-CAH can be found that have less deleterious effects on enzyme activity. Other less-common defects in enzymes of cortisol synthesis can be associated with moderately elevated 17-OHP. Precocious puberty, acne, hirsutism and subfertility are the commonest features of hyperandrogenism. 17-OHP is a diagnostic marker for CAH but opinions differ on the role of 17OHP or androstenedione in monitoring treatment with renin in the salt losing form. This review considers the utility of 17-OHP measurements in children, adolescents and adults.

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A Diagnosis Not to Be Missed: Nonclassic Steroid 11β-Hydroxylase Deficiency Presenting With Premature Adrenarche and Hirsutism

Cited by 62 publications

References 24 publications

Genetics of Congenital Adrenal Hyperplasia

Genetics of Congenital Adrenal Hyperplasia

Premature Adrenarche - A Common Condition with Variable Presentation

17-Hydroxyprogesterone in children, adolescents and adults

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