Endocrine Functioning in Multitransfused Prepubertal Patients with Homozygous β-Thalassemia

Masala, A.; Meloni, T; Gallisai, D.; Rovasio, P. P.; Rassu, S.P.G.; Milia, Anna Franca

doi:10.1210/jcem-58-4-667

Cited by 82 publications

(69 citation statements)

References 5 publications

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“…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

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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...

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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

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“…Both normal (7,8) and subnormal GH response (9,10) to provocative stimulation tests have been reported. Some of those with normal GH response to provocation have neurosecretory dysfunction of GH secretion (9,11,12).…”

Section: Introductionmentioning

confidence: 99%

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

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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.

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“…Other factors such as endocrine may play a role in the growth retardation. [9][10][11][12] Nevertheless, other workers were able to keep the growth of thalassemic children within normal or near-normal range by early regular blood transfusions. Iron overload is a regular problem in the management of thalassemia major.…”

Section: Discussionmentioning

confidence: 99%

Experience with Thalassemia Major in Al Baha

Dammas

Adedoyin

Cheriya

1995

Annals of Saudi Medicine

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In a two-year retrospective review of the thalassemia program in our hospital, relevant clinical and laboratory items of information were extracted and analyzed. There were 12 regular attendants; seven males and five females, with a mean age of 6.9 ± 3.3 years and a mean age at the time of diagnosis of 18.6 ± 8.7 months. Mean hemoglobin at diagnosis was 6.5 + 1.1 g/dL and MCV was 67.9 ± 4.6 fL. Predominant hemoglobin was HbF (30% to 98%). Presenting features included pallor, abdominal distention, hepatomegaly, splenomegaly and occasional fever. Mean pretransfusion hemoglobin was 8.3 ± 1.5 g/dL and mean post-transfusion hemoglobin was 12.2 g/dL. Only two (16.7%) had weight less than the 5 th percentile; six (50%) had weight ≥25 th percentile while eight (66.7%) had height ≥10 th percentile. Mean weight gain per year was 1.3 ± 0.82 kg and linear growth rate was 4.27 ± 1.66 cm. One patient was positive for hepatitis C virus (detected by antibody) and another was positive for both hepatitis B (both antigen and antibody) and C. Apart from admissions for routine blood transfusion, none of the patients were hospitalized for any other morbid events in two years. High serum ferritin level (1482 ± 766 mg/L) despite subcutaneous desferrioxamine remains a problem. Ann Saudi Med 1995;15(6):589-593.

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Endocrine Functioning in Multitransfused Prepubertal Patients with Homozygous β-Thalassemia

Cited by 82 publications

References 5 publications

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

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

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

Experience with Thalassemia Major in Al Baha

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