Endocrine Abstracts

JOINT1473

Background: Aggrecan is the primary proteoglycan of the cartilage growth plate and is encoded by the ACAN gene. Patients with heterozygous pathogenic variants in ACAN often present advanced skeletal maturation and premature epiphyseal fusion leading to short stature. Recently, mutations in the ACAN gene have been recognized as a major cause of idiopathic short stature. Aromatase inhibitors (AI) have been shown to delay skeletal maturation and improve height in patients with idiopathic short stature.

Objective: with the aim of preventing inappropriate skeletal maturation, we evaluated the effect of short-term treatment with an AI on growth, bone age and pubertal maturation in a group of peripubertal boys with ACAN mutations.

Patients and Methods: 7 boys aged 9. 5-13. 1 years and confirmed mutation in the ACAN gene were included in the study. Their mean (±SD) height SDS was -1. 58±0. 79 (range from -2. 83 to -0. 45), bone age 10. 9-13. 6 years, and mean target height -1. 25±0. 76 (range from -1. 71 to 009). Their testicular volume ranged from 2 to 12 ml. All patients were treated with anastrozole at the dose of 1 mg/daily for one year. BA and predicted adult age (PAH) were evaluated using the Bailey&Pinneau method. Informed consent was obtained from all parents or the legal guardians.

Results: After 1 year height SDS increased in 4/7 children (from -0. 21 to -0. 92, from -2. 83 to -1. 92, from -1. 01 to -0. 33 and from -0. 45 to -0. 17) did not change in 2 (from -1. 56 to -1. 54 and from -2. 27 to -2. 20) and worsened in 1(from -1. 77 to -2. 04). Bone age did not progress inappropriately in any of the subjects (range 11. 6-13. 9 years). PAH significantly increased in all subjects from a mean (±SD) of -2. 47±1. 22 to -1. 760±. 82 SDS (P < 0. 005). Puberty progressed in 6/7 children with mean testicular volume increasing from 7. 8±3. 2 to 13. 3±6. 1 ml (P < 0. 01) and remained unchanged in 1 (2 ml). Treatment was well tolerated and did not induce noticeable side effects in any of the subjects

Conclusions: Our preliminary results indicate that treatment with AI prevents excessive bone maturation in boys with Aggrecan deficiency in the peripubertal period. This translates in sustained growth and increase in PAH. Long-term follow-up is needed to verify the effect of AI on adult height in these patients.