Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic, Organic and Isolated Growth Hormone Deficiency, and Multiple Pituitary Hormone Deficiency

Abstract

Background: The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).

Methods: Total 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.

Results: The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.

Conclusion: The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT01604395.

Keywords: Adolescent; Child; Combined Pituitary Hormone Deficiency; Growth Hormone; Growth Hormone Deficiency.

Fig. 1. Summary of participants. (A) Participants were selected as those with complete and valid data during the follow-up period from all participants enrolled in the LGS. (B) Participants were divided into four subgroups; idiopathic IGHD, idiopathic MPHD, organic IGHD, and organic MPHD.

LGS = LG Growth Study, GHD = growth hormone deficiency, IGHD = isolated growth hormone deficiency, MPHD = multiple pituitary hormone deficiency.

Fig. 2. Growth responses according to idiopathic vs. organic GHD and isolated vs. MPHD in children and adolescents with GHD during the 3 years of GH treatment. (A) ΔHt SDS, (B) ΔPAH SDS, (C) ΔIGF-1 SDS, and (D) ΔIGFBP-3 SDS. The values are presented as mean ± 95% confident interval. The different lowercase letters on the bars indicate significant differences between subgroups.

Ht = height, SDS = standard deviation score, PAH = predicted adult height, IGF-1 = insulin like growth factor-1, IGFBP-3 = insulin like growth factor-binding protein-3, IGHD = isolated growth hormone deficiency, MPHD = multiple pituitary hormone deficiency. ^**P < 0.01; ^***P < 0.001.

Fig. 3. Growth responses to the 3-year GH treatment in children and adolescents with idiopathic or organic GHD. (A) ΔBone age, (B) ΔBMI SDS, (C) ΔHt SDS, (D) Ht SDS, (E) Ht SDS minus MPH SDS, (F) IGF-1 SDS, and (G) IGFBP-3 SDS. All values are presented as mean ± 95% confident interval. The different lowercase letters indicate significant differences between groups.

GH = growth hormone, GHD = growth hormone deficiency, BMI = body mass index, SDS = standard deviation score; Ht = height, MPH = mid-parental height, IGF-1 = insulin like growth factor-1, IGFBP-3 = insulin like growth factor-binding protein-3. ^*P < 0.05; ^**P < 0.01; ^***P < 0.001.