ESPE Abstracts (2016) 86 P-P1-145

To Study the Efficacy and Safety of Growth Hormone (GH) Therapy in Children with Pycnodysostosis

Zainab Mohameda,b, Pooja Sachdevb, Imran Zamira, Joanna Bensonb, Louise Denvirb, M Zulf Mughala & Tabitha Randellb


aRoyal Manchester Children’s Hospital, Central Manchester University Hospital NHS Trust, Manchester, UK; bDepartment of Paediatric Endocrinology and Diabetes, Nottingham Children’s Hospital, Nottingham, UK


Background: Pycnodysostosis is a rare recessive condition with mutation in the cathepsin K gene, causing reduction in bone reabsorption resulting in abnormally dense and fragile bones. Characteristic features include deformity of the skull, maxilla causing craniofacial, dental abnormalities with skeletal changes and short stature. Growth hormone therapy has been attempted in a small group of patients with Pycnodysostosis to promote final adult height, however has not been shown to be efficacious.

Objective: To evaluate the efficacy of GH therapy for short stature in Pycnodysostosis.

Methods: A retrospective analysis of growth data from paediatric outpatient clinic on n=3 children, (two siblings female (A and B aged 16 and 14 year); and one male (C) 15 year). Both siblings received GH (~3 mg/m2 per day) privately from an external center abroad (Europe), for approximately 4 year period along with puberty blocker injections for ~1 to 2 years. Subject (C) received growth hormone (0.4 mg/m2 per day) trial for 4 months at an endocrine center within UK. All patients tested negative for growth hormone deficiency prior to starting GH therapy. Serial anthropometric data pretreatment was compared with that during GH therapy.

Results: The pre-treatment height centile for n=3, was < 1st percentile. Height SDS mean (±S.D.), in (A) pretreatment and end of therapy (–2.23±0.2) and (–2.24±0.4); (B) (–2.9±0.2) and (–3.28±0.3) at 4 years; (C) (–3.8±0.2) and (–3.28±0) at 4 months. The height velocity changed from 5.4 (±0.4) to 5.2 (±1.5); 5.5 (±1.5) to 5.9 (±1.4) cm/year after 4 year treatment in (A) and (B); 5.4 (±2.2) to 5 cm/year after 4 months of treatment in C. IGF1 during GH treatment showed stark rise above normal range. Moreover, BMI z-score worsened on treatment in (A) +1.67 to +1.93 and (B)+2.8 to 3.19 respectively. Symptoms of sleep apnea and insulin resistance worsened on GH therapy, no signs of raised intracranial pressure were noted.

Conclusion: GH therapy failed to show any improvement in growth velocity or height SDS. Increased insulin resistance, weight gain, exponential rise in serum IGF1 level was seen in 2/3 patients raising concerns about its safety. In contrast to previous report this case series shows no beneficial effect from growth hormone therapy. High IGF1 levels are associated with a greater risk for prostate and breast cancer therefore challenging the potential benefit of GH therapy for treatment of short children with skeletal dysmorphology.

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