Impact of Overweight on Effectiveness of Treatment with Human Growth Hormone in Growth Hormone Deficient Children: Analysis of German KIGS Data

Abstract

Background:

We hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests.

Methods:

Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years).

Results:

Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97^th centile; n=71) and moderate overweight children (BMI>90^th to 97^th centile, n=93) demonstrated no significant difference in any parameter.

Conclusions:

Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

Key words

growth hormone deficiency - growth hormone treatment - obesity - prediction model - index of responsiveness

• References

• 1 Argente J, Caballo N, Barrios V et al. Disturbances in the growth hormone-insulin-like growth factor axis in children and adolescents with different eating disorders. Horm Res 1997; 48 (Suppl. 04) 16-18
• 2 Frystyk J, Brick DJ, Gerweck AV et al. Bioactive insulin-like growth factor-I in obesity. J Clin Endocrinol Metab 2009; 94: 3093-3097
• 3 Loche S, Cappa M, Borrelli P et al. Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: evidence for somatomedin-C mediated inhibition. Clin Endocrinol (Oxf) 1987; 27: 145-153
• 4 Stanley TL, Levitsky LL, Grinspoon SK et al. Effect of body mass index on peak growth hormone response to provocative testing in children with short stature. J Clin Endocrinol Metab 2009; 94: 4875-4881
• 5 Reinehr T, Hinney A, de SG et al. Definable somatic disorders in overweight children and adolescents. J Pediatr 2007; 150 (618) 622
• 6 Ranke MB, Lindberg A. Predicting growth in response to growth hormone treatment. Growth Horm IGF Res 2009; 19: 1-11
• 7 Wabitsch M, Heinze E, Debatin KM et al. IGF-I- and IGFBP-3-expression in cultured human preadipocytes and adipocytes. Horm Metab Res 2000; 32: 555-559
• 8 Wabitsch M, Blum WF, Muche R et al. Insulin-like growth factors and their binding proteins before and after weight loss and their associations with hormonal and metabolic parameters in obese adolescent girls. Int J Obes Relat Metab Disord 1996; 20: 1073-1080
• 9 Schweizer R, Martin DD, Schonau E et al. Muscle function improves during growth hormone therapy in short children born small for gestational age: results of a peripheral quantitative computed tomography study on body composition. J Clin Endocrinol Metab 2008; 93: 2978-2983
• 10 Ranke MB, Lindberg A. Approach to predicting the growth response during growth hormone treatment. Acta Paediatr Suppl 1996; 417: 64-65
• 11 Ranke MB, Lindberg A. Predicting growth in response to growth hormone treatment. Growth Horm IGF Res 2009; 19: 1-11
• 12 Lindberg A, Ranke M. Data analyses within KIGS; Growth hormone therapy in pediatrics – 20 years of KIGS. Karger; 2007: 23-28
• 13 Ranke MB, Lindberg A. Observed and predicted growth responses in prepubertal children with growth disorders: guidance of growth hormone treatment by empirical variables. J Clin Endocrinol Metab 2010; 95: 1229-1237
• 14 Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291-303
• 15 Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 45: 13-23
• 16 Prader A, Largo R, Molinari L et al. Physical growth of Swiss children from birth to 20 years of age. Helv Paediatr Acta Suppl 1989; 52: 1-125
• 17 Freeman JV, Cole TJ, Chinn S et al. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995; 73: 17-24
• 18 Cole TJ, Freeman J, Preece M. Body mass index reference curves for the UK, 1990. Arch Dis Child 1995; 73: 25-29
• 19 Juul A, Dalgaard P, Blum WF et al. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995; 80: 2534-2542
• 20 de Ridder MA, Stijnen T, Drop SL et al. Validation of a calibrated prediction model for response to growth hormone treatment in an independent cohort. Horm Res 2006; 66: 13-16
• 21 Reinehr T, Holl RW, Roth CL et al. Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity. Pediatr Diabetes 2005; 6: 5-12
• 22 Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010; 316: 165-171