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

Ultralow-dose dexamethasone to preserve endogenous cortisol stress response in nonclassical congenital adrenal hyperplasia: A new promising treatment

Introduction: Nonclassical congenital adrenal hyperplasia (CAH) is characterized by sufficient cortisol and aldosterone production at the cost of androgen overproduction. Hydrocortisone or dexamethasone in supraphysiological doses are current treatment; however, their downside is suppression of endogenous cortisol production resulting in corticosteroid dependency. We aimed to treat children with nonclassical CAH with a ultralow-dose dexamethasone to normalize androgen levels, without a detrimental effect on endogenous cortisol production. Case Presentation: We recruited five patients diagnosed with nonclassical CAH on the basis of clinical presentatio

Ways to Improve the Diagnosis of Growth Hormone Deficiency

Developmen

Subclassification of small for gestational age children with persistent short stature: Growth patterns and response to GH treatment

Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate differen

Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age

Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone (GH) profiles and fasting insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels after 3 months of GnRHa treatment with those at baseline. Methods: After measurement of baseline overnight profiles and IGF-I and IGFBP-3 levels, 14 short pubertal SGA boys received leuprorelide acetate depots of 3.75 mg subcutaneously, every 4 weeks. Results: At baseline, mean GH levels were comparable with those of controls, whereas IGF-I and IGFBP-3 standard deviation scores (SDS) were significantly lower than zero SDS. After 3 months of GnRHa treatment, all boys showed clinical arrest of puberty. The area under the curve above zero, mean and maximum LH and FSH had significantly decreased to prepubertal levels. Peak LH during the GnRH agonist test, however, indicated insufficient pubertal suppression in 43% of boys. Overnight GH profile characteristics and IGF-I and IGFBP-3 levels did not significantly change. Conclusions: Puberty was sufficiently suppressed by GnRHa treatment, as shown by the prepubertal LH and FSH profiles. After 3 months of GnRHa treatment, overnight GH profile characteristics had not significantly changed, reflecting that GH levels are comparable for prepubertal and early pubertal boys