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

Abstract

Growth retardation in children with thalassaemia major is multifactorial. We 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 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly 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 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

“…For GH, we found a strong positive correlation between peak responses during ITT and GST, which was comparable to the results of Spathis et al (21). Soliman et al concluded previously that glucagon was at least as good as the ITT in stimulating GH release (27). Moreover, Aimaretti et al found that although the ITT was a more effective stimulus than L-arginine, L-dopa, and clonidine, glucagon was the strongest stimulus after ITT (28).…”

Growth pattern in children with beta-thalassemia major and its relation with serum ferritin, IGF1 and IGFBP3

“…Serum parameters of group 2 of patients with BTM, in our study were insignificantly different from their control group 4 except as regard serum ferritin; this ferritin was accused in several studies before to be the cause of short stature and decreased their serum levels of IGF-1 and its binding protein IGFBP-3. 16 In our study there was no correlation between serum ferritin and any other variable of the patients with BTM, the result which agreed with that of Karydis et al 2004 21 and that of Vedergor et al 2007, 22 who found no significant correlation between serum ferritin and the peak levels of GH or IGF1. In our study there was a statistically significant correlation between T4 and upper/lower segment ratio, this result could be explained by the known effect of thyroid hormone on the body proportions.…”

“…IGFBP3 in our study was also statistically significantly lower than in the control group p<0.05, the result which agreed with that of Chrysis et al 2001 13 who found low levels of IGF1 and IGFBP3 in their thalassemia patients with short stature and decelerated growth compared to those with normal growth. Not all of our thalassemia patients were with retarded linear growth, 57.6 % were below the 5th percentile for age and sex (BTM group1), the mean age of them was higher than the rest of the group (BTM group 2), Soliman et al 1999 16 reported that after the age of four, there is significant growth retardation involved short stature and sitting height. This age difference between the two thalassemia groups in our study, may explain the insignificant difference between the two groups as regard serum levels of IGF1 and IGFBP3, as IGF1 and IGFBP3 are known to increase slowly with age in childhood, reaching a peak level at puberty and decrease thereafter.…”

Basal and Stimulated Levels of Growth Hormone, Insulin-like Growth Factor-I (IGF-I), IGF-I Binding and IGF-Binding Proteins in Beta-Thaiassemia Majo

“…Conflicting results have been reported with respect to pituitary secretion of GH and its regulation from the hypothalamus 14 " 22 . Conflicting results have been reported with respect to pituitary secretion of GH and its regulation from the hypothalamus 14 " 22 .…”