In patients with b-
thalassemia major (TM), the anterior pituitary gland is particularly sensitive to
free radical stresses. It has been reported that the GH deficiency (GHD) may be secondary to either pituitary or hypothalamic dysfunction. The duration of the disease, the patient's age and the severity of
iron overload are the most important factors responsible for the defect of
growth hormone (GH) secretion. Recent reports have documented a frequency of severe
growth hormone deficiency in 13%-32% of patients with b-
thalassemia major. All of these patients underwent GH-releasing
hormone (GH-RH) plus
arginine (ARG) testing. We undertook the present study to evaluate the GH and adrenal response during
glucagon stimulation test (GST) in patients with TM because the GH-RH plus ARG test in patients with hypothalamic GHD may be misleading. Thirty-three adult TM patients were recruited (mean age 36.6 years). Fifty four percent were included in the severe GHD group (GH peak below 3mg/l). The
IGF-1 level in TM patients was consistently low (60.3 ± 35.3 mg/l) and 86.6% of patients with a normal GH response to GST had a low
IGF-1 level. These findings are also indicative of a relative resistance to GH. In eight out of 18 TM patients (44.4%), the GHD was associated with
hypogonadotropic hypogonadism. A positive correlation was found between GH peak after GST and
IGF-1 level (r = 0.8, p: 0.003) and a negative correlation between the age of female TM patients and GH peak (r = 0.711, p: 0.007). All patients but one had no evidence of cardiac
iron overload (mean T2* 30.4 ± 8.2 ms; range 14-44 ms). The mean LVEF (%) in TM patients was no different when compared to healthy controls. However, three patients with severe GHD and normal T2*were found to have reduced LVEF.One patient (4%) had a peak
cortisol response to GST compatible to
adrenal insufficiency.
Nausea,
headache and\or
hypoglycemia occurred in 3 patients (12%) during GST. In conclusion, our study demonstrates that the presence of GHD is frequent in adult TM patients. According to the international guidelines for medical practice, we believe that before considering
hormone replacement therapy, a second test to confirm the diagnosis of GHD and
adrenal insufficiency is required.