Recombinant Human GH Replacement Therapy in Children with Pseudohypoparathyroidism Type Ia: First Study on the Effect on Growth

• Published in: The journal of clinical endocrinology and metabolism 2010-11, Vol.95 (11), p.5011-5017
• Main Authors: Mantovani, Giovanna, Ferrante, Emanuele, Giavoli, Claudia, Linglart, Agnes, Cappa, Marco, Cisternino, Mariangela, Maghnie, Mohamad, Ghizzoni, Lucia, de Sanctis, Luisa, Lania, Andrea G, Beck-Peccoz, Paolo, Spada, Anna
• Format: Article
• Language: English
• Subjects: Body Height - drug effects; Child; Child, Preschool; Female; Human Growth Hormone - therapeutic use; Humans; Male; Pseudohypoparathyroidism - therapy; Recombinant Proteins - therapeutic use; Treatment Outcome
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-1649

Context: Since the identification of GH deficiency due to resistance to GHRH in patients with pseudohypoparathyroidism type Ia (PHP-Ia), no study investigated the effects of recombinant human GH (rhGH) therapy on height velocity (HV) in these patients. Objectives, Patients and Methods: To address this question, eight prepubertal PHP-Ia children with GH deficiency (seven girls and one boy, aged 5.8–12 yr) underwent a 3- to 8-yr treatment with rhGH. Height and HV were measured before and at 6-month intervals during therapy. Nine sex- and age-matched children with idiopathic GH deficiency were monitored during rhGH therapy for comparison. Results: In PHP-Ia children, height sd scores increased from −2.4 ± 0.58 to −1.8 ± 0.47 (P = 0.04) after 12 months, this increase being maintained after the second (−1.6 ± 0.6) and third (−1.15 ± 0.6) year of therapy, similarly to what recorded in children with idiopathic GH deficiency. The HV and HV sd scores after 3 yr maintained a significant increase from 3.5 ± 0.6 to 7.0 ± 0.9 cm/yr (P < 0.0001) and from −2.8 ± 0.8 to +2.2 ± 1.0 (P < 0.0001), respectively. Six patients treated for 4–8 yr had a reduced pubertal spurt and did not improve their near-adult height, with the only exception of one patient in whom estrogen production was blocked by GnRH analogs. Conclusions: We report the first study on the efficacy of rhGH replacement therapy in prepubertal children with PHP-Ia and provide indication that treatment of GH deficiency should be started soon due to the rather limited time window for a potentially effective therapy. The effects of rhGH replacement therapy in children with PHP-Ia suggest that an increase in height velocity during rhGH treatment may be achieved before the onset of puberty.