No abstract

The causes of growth retardation of children with thalassaemia major are multifactorial. We studied the GH response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, IGF-I, IGF-binding protein-3 (IGFBP-3) and ferritin, and evaluated IGF-I generation after a single dose of GH (0.1 mg/kg per dose) in 15 prepubertal patients with thalassaemia, 15 age-matched children with constitutional short stature (CSS) (height standard deviation score less than ¹2, with normal GH response to provocation) and 11 children with isolated GH deficiency (GHD). Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (6:2 Ϯ 2:3 and 6:8 Ϯ 2:1 mg/l respectively) than the CSS group (18:6 Ϯ 2:7 and 16:7 Ϯ 3:7 mg/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 (47:5 Ϯ 19 ng/ml and 1:2 Ϯ 0:27 mg/l respectively) compared with those with CSS (153 Ϯ 42 ng/ ml and 2:06 Ϯ 0:37 mg/l respectively), but the IGF-I and IGFBP-3 concentrations were not different from those with GHD (56 Ϯ 25 ng/ml and 1:1 Ϯ 0:32 mg/l respectively). These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective. Serum ferritin concentration correlated significantly with GH peak response to provocation (r ¼ ¹0:36, P < 0:05) and circulating IGF-I (r ¼ ¹0:47, P < 0:01) and IGFBP-3 (r ¼ ¹0:42, P < 0:01) concentrations. In the IGF-I generation test, after GH injection, the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86:7 Ϯ 11:2 ng/ml and 2:05 Ϯ 0:51 mg/l respectively) than those in the CSS group (226 Ϯ 45:4 ng/ ml and 2:8 Ϯ 0:43 mg/l respectively). The IGF-I response was significantly higher in children with GHD (158 Ϯ 50 ng/ml) than in thalassaemic children. Six short (height standard deviation score less than ¹2) thalassaemic children who had defective GH response to provocation (<10 mg/l), all the children with GHD and eight short normal children (CSS) were treated for 1 year with human GH (18 units/m 2 per week divided into daily s.c. doses). After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children (from 3:8 Ϯ 0:6 cm/year to 7:2 Ϯ 0:8 cm/year) and controls. However, the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children (3:3 Ϯ 0:3 cm/year increment) compared with those with CSS (5:3 Ϯ 0:4 cm/year increment) and GHD (6:9 Ϯ 1:2 cm/year increment) (P < 0:05). Their circulating IGF-I concentration (105 Ϯ 36 ng/ml) was significantly lower than those for CSS (246 Ϯ 58 ng/ml) and GHD (189 Ϯ 52 ng/ml) after 1 year of GH therapy. These data prove that some children with b-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH.

No abstract

Serum growth hormone (GH), cortisol, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and insulin like growth factor I (IGF-I) concentrations were measured in 15 children with sickle cell disease (SCD) together with their heights < 5th percentile for age and gender, and in 15 healthy age-matched children who had normal variant short stature (NVSS). GH response to an oral dose of clonidine (0.15 mg/m2) and cortisol response to ACTH stimulation were determined in the two groups. Children with SCD had significantly lower serum concentrations of IGF-I and decreased GH response to stimulation. Eight out of the 15 children with SCD did not mount an appropriate GH response to clonidine provocation (> 10 micrograms/l). CT scanning of the hypothalamic-pituitary area in those eight children with SCD revealed a partial or complete empty sella in all of them. It appears that defective GH release, and consequently low IGF-I production and slow growth velocity in children with SCD might be secondary to hypoxic-vascular insults to their hypothalamic-pituitary axis during one or more of the sickling episodes.