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

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. (J Clin Endocrinol Metab 95: 5011-5017, 2010)