title: Growth hormone and adrenal response to intramuscular glucagon test and its relationship to IGF-1 production and left ventricular ejection fraction in adult B-thalassemia major patients.
abstract: 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.
authors.affiliation: Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Viale Cavour, Ferrara, Italy. vdesanctis@libero.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Sanctis
authors.forename: Nicos
authors.initials: N
authors.lastname: Skordis
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Galati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Raiola
authors.forename: Michela
authors.initials: M
authors.lastname: Giovannini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Candini
authors.forename: Katerina
authors.initials: K
authors.lastname: Kaffe
authors.forename: Irene
authors.initials: I
authors.lastname: Savvides
authors.forename: Soteroulla
authors.initials: S
authors.lastname: Christou
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D015897:Comorbidity; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D005934:Glucagon / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood* / Q000172:deficiency; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism*; D046150:Laron Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume / Q000502:physiology*; D055815:Young Adult; D017086:beta-Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism
chemical_list: D005765:Gastrointestinal Agents; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005934:Glucagon