Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth

Growth retardation in children with thalassaemia major is multifactorial. W e studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (1GFBP3), and ferritin, and evaluated the spontaneous nocturnal (12h) GH secretion in prepubertal patie nts with thalassaemia and age-matched children with constitutional short st ature (CSS) (height SDS < -2, but normal GH response to provocation). The a natomy of the hypothalamic pituitary area was studied in patients with abno rmal GH secretion using IMRI scanning, Children with thalassaemia had signi ficantly lower peak GH response to provocation by clonidine and glucagon (8 .8 +/- 2.3 mu g/l and 8.2 +/- 3.1 mu g/l respectively) than did controls (1 7.6 +/- 2.7 mu g/l and 15.7 +/- 3.7 mu g/l respectively). They had signific antly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 4 2 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic chi ldren had a GH peak response of < 7 mu g/l after provocation, Those with a normal GH response after provocation also had significantly lower IGF-I and 1GFBP3 concentrations than controls. Analysis of their spontaneous nocturn al GH secretion revealed lower mean (2.9 +/- 1.77 mu g/l) and integrated (2 .53 +/- 1.6 mu g/l) concentrations compared to controls (4.9 +/- 0.29 mu g/ l and 5.6 +/- 0.52 mu g/l respectively). Five of them had mean nocturnal GH concentration <2 mu g/l and four had maximum nocturnal peak below 10 mu g/ l. These data denoted defective spontaneous GH secretion in some of these p atients. MRI studies revealed complete empty sella (n = 2), marked diminuti on of the pituitary size (n = 4), thinning of the pituitary stalk (rt = 3) with its; posterior displacement (n = 2), and evidence of iron deposition i n the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9), Serum ferritin concentration was correlated signific antly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.4 3, p < 0.01) concentrations. These data prove a high prevalence of defectiv e GH secretion in thalassaemic children associated with structural abnormal ity of their pituitary gland.