ESPE2022 Top 20 Posters Section (20 abstracts)
Aromatase Inhibitor (anastrazole) vs placebo delays bone age maturation in prepubertal children with Silver Russell or Prader-Willi Syndrome and pathological adrenarche
Marie-Noëlle Dufourg 1 , Gwenaelle Diene 2 , Marine Cachanado 3 , Thuy-Ai Vu-Hong 1 , Laurence Berard 3 , Alexendra Rousseau 3 , Nora Soussi 3 , Graziella Pinto 4 , Stéphanie Rouleau 5 , Delphine Bernoux 6 , François Chalard 7 , Hubert Ducou Le Pointe 7 , Antonin Lamaziere 8 , Maite Tauber 2 & Irène Netchine 1
1Pediatric Endocrinology, Hôpital Trousseau, Sorbonne Université, Paris, France; 2Höpital des Enfants, Toulouse, France; 3URC Saint-Antoine, Paris, France; 4Hôpital Necker Enfants Malades, Paris, France; 5CHU Angers, Angers, France; 6Hôpital Femme Mère Enfant-HCl, Lyon, France; 7Radiology, Hôpital Trousseau, Paris, France; 8Spectrometry, Hôpital Saint Antoine, Paris, France
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.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more