Improving a low birth rate in females with SW 21-OHD remains a problem and new approaches are required. If the mother has 21-OHD (even nonclassical 21-OHD), pre-conception counselling and paternal genotyping are advisable and prenatal dexamethasone therapy should be considered.
Background: We present a 12-year-old girl with a 5-year history of progressive virilization. Results: Regarding elevated plasma levels of 17-hydroxyprogesterone (17-OHP) and androgens, normal ultrasound and CT scan of ovaries and adrenal glands, the nonclassic form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency was presumed the cause of virilization. As the glucocorticoid therapy did not normalize high levels of 17-OHP and androgens, and the DNA analysis did not demonstrate a mutation causing CAH, a laparotomy was performed. Near the right ovary a tumor was found and extirpated. Pathohistological studies determined it to be a rare steroid cell tumor, ‘not otherwise specified’. Within the next months the signs of virilization resolved and menarche occurred. Conclusions: Steroid cell tumor should be considered in differential diagnosis of virilization in childhood. Regarding the age of our patient and pathohistological findings of the tumor, her prognosis is favorable.
Background: Most patients with 21-hydroxylase deficiency (21-OHD) are compound heterozygous carriers. Their phenotype usually reflects a less severe allelic mutation, although discordance between the genotype and the phenotype has been observed. Case Report: We present 5 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD belonging to the 3 generations of the same family (grandmother, parents and their 2 children). As each patient carries at least one mild mutation of the CYP21 gene, their genotypes correspond to nonclassical CAH. The propositus is the older brother, who is compound heterozygous with a mild and severe CYP21 mutation (P30L/R356W). In spite of one mild CYP21 mutation, he presented with the clinical picture of a simple virilizing form of 21-OHD and required glucocorticoid replacement therapy from the age of 4. Both probands’ parents are compound heterozygous carriers of different CYP21 gene mutations causing various degrees of enzymatic activity impairment, which explains the different genotypes and phenotypes in their offspring. The probands’ mother, besides the nonclassical 21-OHD, also had neuroblastoma of the adrenal gland. Conclusion: The potential discordance between the genotype and the phenotype in some patients with CAH is emphasized. The existence of a mild CYP21 mutation P30L in a compound heterozygous with CAH might be associated with progressive virilization requiring glucocorticoid therapy from early childhood. The occurrence of neuroblastoma with 21-OHD may support the hypothesis that an impairment in the synthesis and secretion of glucocorticoids may play role in the development and functioning of the adrenal medulla.
This is the first report of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency in Croatia in which the patients have been evaluated clinically, hormonally, and by molecular genetic analysis. Genetic analysis was performed on 18 Croatian patients with nonclassic CAH due to 21-OH deficiency using allele-specific PCR. ACTH stimulation testing and HLA typing were used to evaluate patients hormonally. Molecular genetic analysis revealed a variety of mutations in individuals with different clinical symptoms, including precocious pubarche, hirsutism, (dysmenorrhea, subfertility and clitoromegaly. Serum stimulated 17-hydroxyprogesterone (17-OHP) levels indicated that all patients fell within the acceptable range for nonclassic congenital adrenal hyperplasia. Clinical and genetic analysis confirmed nonclassic 21-OH deficiency in our Croatian sample of ten males and eight females. This study shows that genotype does not necessarily predict fertility status in our group of affected patients.
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