ESPE Abstracts

Background: Non-classic congenital adrenal hyperplasia (NC-CAH) is caused by pathogenic variants of the CYP21A2 gene, and in most cases is not associated with cortisol deficiency as is the classic (severe) form. The majority of children with NC-CAH are asymptomatic and do not require cortisol replacement therapy with hydrocortisone unless they develop symptoms of hyperandrogenemia such as early pubarche, growth acceleration, advanced bone age, and ultimately short stature. Elevated estrogen levels through aromatization of excess levels of adrenal androgen causes rapid bone maturation and early epiphyseal closure. Third-generation aromatase inhibitors (AI), such as anastrozole and letrozole, which block the conversion of androgens to estrogens, have been used off-label in males with short stature to delay bone maturation and as an adjunct therapy in children with classic CAH. The use of AI as monotherapy for children with NC-CAH has never been reported.

Case Series: We present three female children with a diagnosis of NC-CAH who were treated with anastrozole monotherapy as they presented with advanced bone age and early pubarche, but no signs of genital virilization. Hydrocortisone was not used as all four children had normal peak cortisol in response to ACTH stimulation testing. Age of children at initiation of anastrozole therapy were 3.7, 3.9, and 6.7 years with bone age z-scores of 6.4, 1.9 and 2.9, respectively. Bone age Z-scores at the end of Anastrozole therapy were -0.75, 0.52 and -0.07. Height z-scores were corrected for bone age at initiation of Anastrozole. While on therapy, bone age z-scores decreased (see Figure 1); all three patients reached or exceeded their target height.

Discussion: Monotherapy with AI can be an effective alternative in slowing down bone maturation and improving height outcomes in children with NC-CAH and normal adrenal cortisol production. All three patients had appropriate pubertal progression, normal ovarian ultrasounds, and normal bone mineral density accrual.