The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene.
Clin Endocrinol (Oxf)
; 82(4): 543-9, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25041270
ABSTRACT
BACKGROUND:
Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable.OBJECTIVES:
(i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH. PATIENTS ANDMETHODS:
The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects.RESULTS:
The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml).CONCLUSIONS:
NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Steroid 21-Hydroxylase
/
Adrenal Hyperplasia, Congenital
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Mutation
Type of study:
Diagnostic_studies
Limits:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
/
Middle aged
Language:
En
Journal:
Clin Endocrinol (Oxf)
Year:
2015
Type:
Article
Affiliation country:
Greece