ESPE2022 Top 20 Posters Section (20 abstracts)
Background: Silver Russell syndrome (SRS) is a rare imprinting disorder with prenatal and postnatal growth retardation and feeding difficulties. The main molecular causes are loss of methylation of the 11p15.5 imprinting control region (H19/IGF2) and maternal uniparental disomy of chromosome 7. Prader-Willi syndrome (PWS) is a complex neurodevelopmental imprinting disorder with neonatal muscular hypotonia, failure to thrive to insatiable appetite, short stature and impaired cognitive function, secondary to molecular anomalies in the 15q11q13 region. In both syndromes, rapid bone age maturation can occur even in the absence of central puberty during pathological adrenarche. Androgens after aromatisation in estrogens are leading to bone maturation and can produce premature epiphyseal fusion. There is currently no drug with a pediatric authorization capable of limiting the advance in bone maturation secondary to adrenarche. Aromatase inhibitors, used for the treatment of hormone-dependent cancers, block the transformation of androgens into estrogens. Third generation inhibitors, such as Anastrozole, have been used in a few clinical trials to limit bone maturation and improve final height, notably in children treated with growth hormone (GH) due to a GH deficit. Nevertheless, the data reported do not include children with pathological adrenarche.
Objective: This study evaluates the effectiveness of an aromatase inhibitor during pathological adrenarche in prepubertal children with SRS or PWS to delay their bone age maturation.
Methods: The study included 25 prepubertal patients with SRS or PWS, treated with GH. “Pathological” adrenarche was defined either by an SDHEA value higher than the normal values according to age, or by pubic hair, associated with a bone age at least equal to the chronological age. Patients were randomized double-blind with 2 treatment arms: Anastrazole (1 mg/day) vs placebo, for a period of 18 months. The primary endpoint was the rate of progression of bone maturation, assessed on hand and wrist X-rays.
Findings: Bone age progresses by 9.5 months (0-41 months) in the Anatrazole group and by 12 months (0-30 months) in the Placebo group when the bone age is read according to the method based on Greulich and Pyle atlas (P=0.43). When the BoneXpert computer-automated bone age determination method is used, bone age increases significantly more, in 18 months in the Placebo group than in the Anastrazole group (absolute difference of 8.46 months) (P=0.01). No serious adverse effects were observed.
Conclusion: Anastrazole, an aromatase inhibitor, is effective in slowing bone maturation during pathological adrenarche in patients with SRS or PWS.
15 Sep 2022 - 17 Sep 2022