Prevalence of Nonclassic Congenital Adrenal Hyperplasia in Turkish Children Presenting with Premature Pubarche, Hirsutism, or Oligomenorrhoea

Abstract

Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum of CYP21A2 mutations in NCAH patients. Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL. Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous. Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent.

LC–MS/MS based determination of basal- and ACTH-stimulated plasma concentrations of 11 steroid hormones: implications for detecting heterozygote CYP21A2 mutation carriers

“…On the one hand, this can be valuable under conditions in which hormone determinations are possible but access to genetic testing is limited due to financial restrictions of health care systems or health insurances. Since heterozygosity of CYP21A2 gene mutations has to be considered in the differential diagnosis of hyperandrogenism (7,8,9,10) and since the ACTH test is often performed in these clinical situations (24, 7), calculation of ((17OHPC 21S)/F!1000) provides important additional information for test interpretation and diagnostic workup.…”

“…Little data on heterozygote rates has been published. Based on heterozygosity of CYP21A2 gene mutations has been documented in premature pubarche (9,10). Therefore, heterozygosity of CYP21A2 gene mutations has to be considered in the differential diagnosis of hyperandrogenemic symptoms.…”

Congenital Adrenal Hyperplasia

“…30 Nevertheless, CAH is an uncommon cause of premature adrenarche. 31 Among children with premature pubarche, the diagnosis of CAH can be suspected when basal 17-OHP, androstenedione, and testosterone concentrations are elevated and/or bone age is advanced. 32 Although a cut-point of basal 17-OHP value > 200 ng/dl has been suggested, some patients with non-classic CAH may be overlooked using this value.…”

Non-Classical Congenital Adrenal Hyperplasia in Childhood

“…Heterozygote non-classical 21-hydroxylase gene mutation was detected in 8.3% of the girls with premature pubarche (19). CYP21A2 mutation was detected in 4.7% of the 126 subjects (122 girls, 4 boys) with premature pubarche, hirsutism, or polycystic ovary syndrome (PCOS) presentation (20). Increased penile length can be observed among boys.…”

“…It may be difficult to distinguish the clinical symptoms and findings of premature adrenarche from those of PCOS in girls (20). Although a high 17-OHP level is diagnostic in classical CAH cases, this finding may be insufficient for a diagnosis of NCCAH.…”