Short children born small for gestational age (SGA) : puberty, hormonal profiles, combined GnRHa and GH treatment and (epi)genetics of 2 IGFBP gene promotors

In the Netherlands, children who remain short after being born small for gestational age (SGA) are treated with growth hormone (GH). The clinical studies described in this thesis focused on treatment options in short children born SGA who came under medical attention around pubertal age. These children were treated with a GnRH analogue (GnRHa) for 2 years to postpone puberty. After 3 months of GnRHa treatment, the efficacy of this treatment was investigated by measuring the spontaneous luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion. Furthermore, the influence of GnRHa treatment on spontaneous GH secretion and insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels was investigated. After 3 months of GnRHa treatment, GH treatment 1 vs. 2 mg/m2/day was started. During a study period of 2 years, GH, IFG-I and IGFBP-3 levels were measured. Furthermore, safety parameters including insulin sensitivity, body composition and lipid profile were investigated. In addition, genotyping of 2 single nucleotide polymorphisms (SNPs) in the promoter region of the IGFBP3 gene and of 1 SNP in the promoter region of the IGFBP1 gene was performed in a large cohort of short children and short young adults born SGA. Genetic variation in these genes was associated with clinical parameters including IGFBP-3 and IGFBP-1 levels, spontaneous growth as well as growth response during GH treatment.