Characteristics and prevalence of non-classical congenital adrenal hyperplasia with a V281l mutation in patients with premature pubarche

Abstract

We aimed to determine the prevalence and clinical characteristics of non-classical congenital adrenal hyperplasia (NCCAH) with V281L mutation in patients with premature pubarche. An adrenocorticotrophic hormone (ACTH) stimu lation test was performed in 14 of the 159 patients with premature pubarche (PP). Patients whose stimulated 17 α -hydroxyprogesterone (17-OHP) level on the ACTH test was ≥ 10 ng/mL underwent a mutational analysis of the CYP21 gene. NCCAH was defi ned in nine (5.7 % ) patients, all of whom had the V281L mutation. Four of the NCCAH patients were homozygote and four of them were heterozygote. One other patient was compound heterozygote for V281L mutation and the I2 splice mutation. One of the patients with V281L heterozygous mutation developed true precocious puberty and the other one had rapid progressive early puberty and developed polycystic ovary syndrome. ACTH stimulated 17-OHP ≥ 10 ng/mL in PP patients is load star to mutation analysis and heterozygote patients should be followed for clinical and biological hyperandrogenism up to completion of the whole ' genome sequence ' .

Basal levels of 17-hydroxyprogesterone can distinguish children with isolated precocious pubarche

“…However, it is important to exclude NCCAH to warrant the correct treatment and to avoid related medical problems 3,14 . In our cohort, prevalence of NCCAH was 7.6% (7/92), similar to that found in other cohorts with low prevalence of NCCAH 15,16 .…”

“…In our prospective study, among the clinical parameters, only accelerated bone age maturation was significantly different in patients with NCCAH, as previously reported 15 . However, obesity is frequently associated with bone age acceleration, and given the strong increase of prevalence of pediatric obesity and, in particular, its association with premature pubertal development, we do not think that this parameter could be useful in clinical practice 20 .…”

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

“…We examined all IPP patients, and the six patients for whom NCAH was diagnosed as the cause of PP, in an effort to identify factors predictive of NCAH development. Most prior studies have proposed that patients with NCAH exhibit accelerated bone-age maturation [23, 29–31] and increased basal or stimulated levels of 17-OHP [29, 32, 33]. In the present study, as expected, the basal and stimulated levels of 17-OHP were higher ( P < 0.001), and the bone-age SD was more advanced ( P < 0.05), in children with NCAH.…”

“…As found previously, the Q318X mutation was also noted in patients presenting with PCOS [22, 41]. Erdeve et al [23] detected the V281L mutation in all PP patients of a Turkish population and suggested that the condition was caused by this mutation rather than other known mutations. Moreover, it has been reported that the V281L mutation is the most common mutation in Turkish patients with PP, PCOS, and hirsutism [25, 27].…”

“…Few data have been gathered on the prevalence of NCAH in Turkish PP patients. Erdeve et al [23] studied 159 patients, and Gonc et al [24] reported 186 patients; the prevalences of non-classical CAH were 5.7% and 3.2%, respectively. In our cohort, six patients (4.7%) were diagnosed with NCAH based on the genetic analysis.…”