Height Gain at Adult-Height Age in 184 Short Patients Treated with Growth Hormone from Prepubertal Age to Near Adult-Height Age is Not Related to GH Secretory Status at GH Therapy Onset

Abstract

Background: GH release after stimuli classifies short children as severe idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for gestational age (AGA) or small for gestational age (SGA). GH release after stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS). Aim: To compare height gain induced by GH therapy (31.8 ± 3.5 µg/kg/day, 7.7 ± 1.6 years) started at prepubertal age and stopped at near adult-height age. Methods: A retrospective longitudinal multicenter study including184 short patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was evaluated throughout GH therapy and at adult-height age. Results: Height-SDS gain at adult-height age was similar among severe IIGHD (1.8 ± 0.8 SDS), mild IIGHD (1.6 ± 0.6 SDS), DGHR (1.7 ± 0.7 SDS) and NGHR (1.6 ± 0.7 SDS), or among IIGHD (1.7 ± 0.7 SDS), ISS (1.7 ± 0.6 SDS) and SGA (1.6 ± 0.8 SD). Conclusion: GH-release stimuli are of little help for deciding on GH therapy in the clinical management of prepubertal children with IIGHD, ISS or SGA.

Validation of Prediction Models for Near Adult Height in Children with Idiopathic Growth Hormone Deficiency Treated with Growth Hormone: A Belgian Registry Study

“…In the last decades, several prediction models for nFAH in GHD patients treated with GH have been developed [6,16,17,18,19,20,21]. Thomas et al [16] developed a model based on a rather small cohort (n = 61) of Belgian GHD children.…”

“…De Ridder et al [18] analyzed the data of the Dutch growth database and described models for prepubertal and pubertal children at the start and after the first year of GH treatment. Carrascosa et al [19] retrieved data from 184 Spanish children from different medical centers and described a model at the end of the second treatment year as well as a model at the onset of the pubertal growth spurt, predicting the Ht SDS gain to be achieved at adult height age. Blethen et al [20] described a model derived from the Genentech study (n = 121).…”

“…Cutfield et al [21] developed models for children with isolated GHD (n = 1,091) and MPHD (n = 604) based on the KIGS database. These models could not be validated in our Belgian cohort because they did not include the first-year response [12,17,18,19,20,21], they used several parameters that were not always available in the Belgian Registry (e.g. bone age within 3 months of GH start [18], BMI, and height at the onset of the pubertal growth spurt [19]), and/or because they included patients treated with only 3 doses of GH per week [17,20], and/or because they contain parameters not usable to predict adult height at 1 year of GH treatment, such as the total duration of GH treatment [20,21] and the 2-year growth response to GH [19].…”

Three-Year Growth Response to Growth Hormone Treatment in Very Young Children Born Small for Gestational Age—Data from KIGS

“…GH secretion estimated by GH max peak during provocative tests did not enter the model. Recently, Carrascosa et al (24) found no difference in height gain to adult age among patients with different GH secretion status on GH treatment, including short children born SGA, suggesting that GH secretion estimated during provocative tests are of little help when GH therapy is decided. Considering the benefits of GH treatment and the care with safety issues, these findings reinforce the need of continuous search for the best predictors of growth response and individualization of GH dosing (25).…”

Personalized Approach to Growth Hormone Treatment: Clinical Use of Growth Prediction Models

“…In a Spanish cohort of 184 children, part of a larger cohort [18] with idiopathic GHD, ISS or SGA, treatment with GH in an average dosage of 32 µg/kg/day up to AH resulted in a similar AH (0.4-0.5 standard deviation (SD) below TH) and AH gain (1.6-1.7 SD), irrespective of diagnosis [19]. In the Netherlands, France and Japan, where generally lower GH doses have been used, average AH was 1.6-2 SD lower than TH [20,21,22].…”