Impaired Growth Hormone (GH) Response to GHReleasing Hormone in Thalassemia Major*

Pintor, C.; Cella, Silvano G.; Manso, Paola; Corda, R.; Dessì, Carlo; Locatelli, Vittorio; Müller, E. E.

doi:10.1210/jcem-62-2-263

Cited by 64 publications

(32 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ten of the 15 children with thalassaemia did not mount an appropriate GH response (>10 mg/l) in both provocation tests. These findings support previous reports indicating impairment of function along the hypothalamic-pituitary growth axis (9)(10)(11)(12)28). In malnourished children with decreased IGF-I synthesis, the basal and stimulated GH levels are significantly higher than normal (29), indicating stimulation of their hypothalamic-pituitary axis by the low circulating concentrations of IGF-I.…”

Section: Discussionsupporting

confidence: 90%

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

Soliman

Banna

Ansari

1998

European Journal of Endocrinology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

Soliman

Banna

Ansari

1998

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…others indicate either a reduced GH secretion following Our results concur with those of other authors 28 which stimulation with GHRH [21][22][23] or a reduced spontaneous GH showed a growth improvement in non-transplanted thalassecretion all day with a low number of pulses and reduced semic patients submitted to long-term treatment with rhGH. mean pulse amplitude.…”

Section: Responder Group Non-responder Groupsupporting

confidence: 92%

Growth after recombinant human growth hormone (rhGH) treatment in transplanted thalassemic patients

Simone

Bartolomeo

Olioso

et al. 1997

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:(BU) and cyclophosphamide (CY) can cure a high percentage of patients with compatible donors. Little is known about the long-term effects of BMT in patients with thalasThe aim of this study was to evaluate the treatment effects with recombinant human growth hormone semia in relation to the growth process as well as endocrine function. (rhGH) in a group of patients after bone marrow transplantation for thalassemia major. At the end of treat-In the present study we have analysed the treatment effects with recombinant human growth hormone (rhGH) ment we divided the subjects into two groups according to the outcome of the therapy: responder and nonin patients after BMT for thalassemia major. responder. Responder group: after 24 months of rhGH administration, growth rate was still significantly higher in respect to start of treatment (P Ͻ 0.0001). Plasma lev- Patients and methods els of IGF-I rose significantly (P Ͻ 0.003). The serum levels of serum asparate aminotransferase (SGOT) andThe study group comprised seven patients (five males, two females) ranging in age from 11.7 to 12.7 years alanine aminotransferase (SGPT) were higher compared to normal values but improved in non-responder (12.06 ± 0.76), affected by thalassemia major and who underwent BMT (mean age at BMT was 7.11 ± 3.31 years) patients. There was no difference in the mean concentration of these parameters before and after treatment in Pescara, Italy. Prior to the referral for BMT all patients had received multiple erythrocyte transfusions. The median (P = NS). Non-responder group: these patients had a worsening of the growth rate during rhGH adminisnumber of tranfusions was 114.71 ± 57.67 (range 13-180). They were administered daily doses of 0.9 IU/kg body tration. There was no increase of the IGF-I levels. Single values of transaminase and ferritin levels were higher weight per week subcutaneously of rhGH (SAIZEN Serono, Rome, Italy) for 24 consecutive months. than in responder patients before and after treatment. There was a significant correlation between IGF-I, Assessment of height, other auxologic parameters and laboratory measures were performed before treatment and SGOT, SGPT and ferritin in all patients before and after therapy. It appears from these data that rhGH at 6 monthly intervals during GH therapy.At the end of treatment we divided the subjects into two administration is worth serious consideration in patients after BMT for thalassemia major presenting impaired groups according to the outcome of the therapy: responder (four boys, one girl) and non-responder (one boy, one girl) growth hormone secretion. This treatment can offer good results only in cases where the normal hepatic synpatients whose height velocity increase was more than 2 cm/year above baseline or less, respectively. thesis of IGF-I is conserved and where liver damage has not reached irreversible conditions, as we have seen inInformed consent for the study was obtained from the patients' parents. the responder group.

show abstract

“…Some studies indicate that patients treated with conventional therapy have normal GH secretion after pharmacological stimuli, 5,6,[16][17][18] while others indicate either reduced GH secretion following stimulation with GHRH [19][20][21] or reduced spontaneous GH secretion all day with a low number of pulses and reduced mean pulse amplitude. 22 In short-stature patients with a normal GH response to provocative stimulation tests, abnormal pulsatile GH secretion has been reported (neurosecretory dysfunction).…”

Section: Discussionmentioning

confidence: 99%

Final height of thalassemic patients who underwent bone marrow transplantation during childhood

Simone

Verrotti

Palumbo

et al. 2001

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:We evaluated the final height achieved by 47 patients who had bone marrow transplantation (BMT) for thalassemia major. Subjects were separated into two groups: patients who received BMT before 7 years of age and patients who received BMT after 7 years of age. Parental height and genetic target height (TH) were calculated. Our data indicated a strict correlation between age at time of transplant and final adult height. The patients whose age at transplant was Ͻ7 years had a less impaired growth rate than did patients who were Ͼ7 years. Moreover, greatest loss in height was observed in subjects who had higher serum levels of transaminase and ferritin and these biochemical parameters were strictly correlated to the final adult height. Mean final adult height, however, did not differ from the genetic target height in subjects who received BMT before 7 years of age and the final height SDS corrected for TH surpasses even the TH. In contrast, the subjects who received BMT after 7 years of age, failed to achieve their full genetic potential. In conclusion, short stature is present in a significant percentage of transplanted thalassemic children. The data in this study indicate a close effect of the age at time of transplant on subsequent growth rate, but the growth impairment in these subjects remain multifactorial. Bone Marrow Transplantation (2001) 28, 201-205. Keywords: bone marrow transplantation; thalassemia major; growth Growth retardation and delayed or absent development are frequently observed in patients with thalassemia major. Growth hormone deficiency is implicated as the cause in some patients, but other factors that could adversely influence growth have also been suggested. Bone marrow transplantation (BMT) following preparation with busulphan (BU) and cyclophosphamide (CY) can cure a high percentage of patients with compatible donors. Little is known about the long-term effects of BMT in patients with thalassemia in relation to the growth process as well as endocrine function. Several studies have considered growth and growth rate in thalassemic children after BMT, but the follow-up was short-term and the final height of these patients is not known.In this study, we evaluated the final height achieved by patients who had bone marrow transplantation for thalassemia major. Patients and methodsOf a cohort of 102 children transplanted for thalassemia major who received an allogeneic BMT from an HLA matched sibling, 47 subjects (28 male, 19 female) who have reached their final adult height, were studied. The criterion for final adult height was either at least 6 months without height gain or documented complete closure of the hand, wrist and iliac crest epiphyses. The mean age of the patients at BMT was 7.05 ± 2.81 years (range 3.11-12.7) and the mean age at the most recent follow-up examination was 20.57 ± 0.63 years (range 18.1-24.2).Subjects were separated into two groups: group Apatients who received BMT before 7 years of age and group B -patients who received BMT after 7 years of age.Prior to ref...

show abstract

Impaired Growth Hormone (GH) Response to GHReleasing Hormone in Thalassemia Major*

Cited by 64 publications

References 21 publications

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

Growth after recombinant human growth hormone (rhGH) treatment in transplanted thalassemic patients

Final height of thalassemic patients who underwent bone marrow transplantation during childhood

Contact Info

Product

Resources

About