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Unlabelled: This study is to estimate the degree of genetic contribution of Fok-I gene polymorphism of Vitamin D receptor to bone mass in patients with thalassaemia. Results indicate a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young thalassemic patients., Introduction: The purpose of this study is to estimate prospectively the degree of genetic contribution of Fok-I gene polymorphism of vitamin D receptor (VDR) to the evolution of bone mass in patients with beta-thalassemia major (b-TH)., Methods: Sixty-four children and young adults (33 males and 31 females) with mean decimal age of 23.20 ± 5.41 (range 9.25-32.41 years) were recruited in this study. All patients were genotyping for Fok-I gene polymorphism and were assessed with dual energy X-ray absorptiometry (DXA) at baseline and 2 years after. Z-scores were calculated based on normal age and sex matched Caucasian population. Metabolites of vitamin D, intact PTH, total calcium, inorganic phosphorous, and alkaline phosphatase were measured at the serum pre-transfusion., Results: A moderate proportion of patients had decreased DXA Z-scores (Z-score ≤-2) predominately in total hip (31 %) and secondary in lumbar spine (15.6 %). Patients being homozygous for the f allele had apparently higher BMD Z-scores compared with those carrying the F allele in homo- or heterozygosity, however, with a difference that did not reached significance. Interestingly enough, a significant deterioration in BMD Z-scores measured at femur (FF: P = 0.004 Ff: P < 0.001, ff: P = 0.024) and total hip (FF: P = 0.022, Ff: P = 0.005) was recorded for all type of genotypes, except for ff genotype and with regard to the total hip DXA values. An increased prevalence of serum 25(OH)D3 deficiency (59.4 %) and 25(OH)D3 borderline (12.5 %) was recorded., Conclusion: Our study indicates a protective role of the f allele of the Fok-I gene polymorphism when found in homozygosity on bone mineral density of young patients with b-TM.

Background: Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated., Objective: To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity., Design and Results: A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00 h ACTH (<1 pg/mL) and cortisol (0·025 μg/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRα of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-κB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes., Conclusions: Our findings indicate that a transient postreceptor defect, or a virus- or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

We performed a systematic neurophysiological evaluation of newborns-infants newly diagnosed with congenital hypothyroidism and started on replacement therapy, in order to document the maturation of visual, auditory and somesthetic pathways and to evaluate the influence of treatment. Twenty-one patients (9 boys, 12 girls) were studied. They underwent neurophysiological evaluation consisting of visual, auditory, and somatosensory evoked potentials at diagnosis, as well as 6 and 12 months after initiation of treatment. At the time of diagnosis, 47.61 % of the patients had abnormal evoked potentials, with visual evoked potentials being most commonly abnormal. Twelve months after the onset of treatment, abnormal evoked potentials were detected in 33.3 % of the patients. In newly diagnosed infants with congenital hypothyroidism there is a high relevance of abnormal evoked potentials (47.61 %) at the time of diagnosis, declining with time and not correlating with the severity of the disease at diagnosis, the time of diagnosis or the initial dose of thyroxine.

Background: Our aim was to retrospectively evaluate the possibility to reduce the number of GH analyses during clonidine and glucagon tests without compromising accuracy., Subjects and Methods: Two hundred and forty-five tests were performed in a total of 188 children and adolescents with a mean age of 9.93 ± 2.88 yr in a single center during the last 5 yr., Results: Ninety-one out of 158 (57.59%) clonidine tests and 47/87 (54.02%) glucagon tests had at least one sample >10 μg/l (negative). For clonidine tests, not measuring GH at 30 min would have resulted in only one negative test missed (0.63% false positive result), whereas not measuring GH both at 0 and 30 min would have increased the false positive percentage to 2.53%. Ending clonidine tests at 90 min would have resulted in 7 negative tests missed (4.43% false positive results). For glucagon tests, more than half of the tests peaked at 120 min (56.32%). Skipping sampling at 0, 60 and 180 min provided a false positive rate of 5.75%., Conclusions: For clonidine tests we can omit blood sampling at time points 0 and 30 min without significantly compromising accuracy.

Background: fl/d3 polymorphism in human GH receptor was correlated with the response to GH therapy in different groups of children with short stature., Aim: This is a 2-yr retrospective study which evaluates the influence of fl/d3 polymorphism to the 1st-and 2nd-year response to GH replacement therapy in Greek children with isolated GH deficiency (GHD)., Subjects and Methods: A total number of 195 pre-pubertal Greek children were studied (121 controls and 74 patients with GH peak <10 ng/ml). Patients with deficiency were treated with exogenous GH at a mean dose of 28.8 μg/kg.d. Multiplex PCR was used to genotype all children for fl/d3 polymorphism, followed by statistical analysis. The main parameters which were used to assess the association of genotype with the response to GH replacement were height SD score (SDS), height gain SDS, and growth velocity (GV) expressed as cm/yr and SDS., Results: Our results revealed that the frequency of d3-homozygosity in the Greek population was 8.26%. No association was detected between the presence or abcense of GHD and genotype. Moreover, no connection between genotype and sex was observed. First-year height SDS, height gain SDS, and GV SDS were significantly higher in d3-carriers (p<0.05). However, this difference did not appear in the 2nd year of treatment., Conclusions: In our study, the d3-polymorphism seems to be associated with a higher efficacy to GH replacement, at least at the beginning of the treatment.

Background: Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese., Methods: A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves., Results: RESULTS showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits., Conclusions: The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention.

Most of the biological actions of vitamin D are mediated by an intracellular receptor (VDR) in which several single nucleotide gene polymorphisms have been identified. Vitamin D deficiency is increasingly identified among thalassemic patients and recent evidence links it with myocardial iron accumulation. The aim of this work was to assess the distribution of the Fok-I polymorphism of the VDR gene among Greek children and young adults with beta-thalassemia major and to investigate its association with 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels. Sixty-nine thalassemic patients (35 females and 34 males), with a mean age of 23·05±6·07 years, participated in the study. Genotype frequencies of Fok-I were similar to those previously reported for other populations; 44·9% of the patients were homozygotes for F allele, 43·5% were heterozygotes and 11·6% were homozygotes for the f allele. Low levels of serum 25(OH)D(3) were recorded, as 41 patients (59·4%) were below the cut-off limit of 50 nmol/l that determines deficiency, whereas, levels of 1,25(OH)(2)D(3) showed wide variability ranging from deficiency (≤50 pmol/l) in 34 patients (49·3%) to excess (≥125 pmol/l) in 13 patients (18·8%). When stratifying patients according to serum 1,25(OH)(2) D(3) concentrations, a higher prevalence of the f allele was observed in the deficiency group (P = 0·03). A comparison of the serum concentrations of the two vitamin D metabolites produced a trend towards a negative correlation (r = -0·204, P = 0·09). Further studies are required to assess the genetic contribution to the regulation of vitamin D metabolites in the serum of patients with beta-thalassemia major.

Background: Children with haematological malignancies such as acute lymphoblastic leukaemia (ALL) may have alteration of bone mineral metabolism therefore increased risk for osteopenia and osteoporosis., Patients and Methods: The purpose of this study was to examine the alterations of bone mineral metabolism in two groups of children (n=42) according to immunophenotyping (B-cell type, T-cell type) both quantitative (bone mineral density z-scores) and qualitative (serum osteocalcin - OC and carboxyl-terminal telopeptide of human type I collagen - ICTP) during diagnosis (T=0), after the intensified chemotherapy period (T=0.5) and the consolidation period (T=1)., Results: According to our results 15 patients had osteopenia and 1 child developed osteoporosis at T=0.5 and 13 patients had osteopenia at T=1. Mean BMD z-score was significantly decreased in both groups during chemotherapy and especially statistically significant decline of T-cell type ALL group compared with B-cell type ALL patients. OC mean level remains in low levels for both groups reaching in plateau during chemotherapy and ICTP level was increased in T-cell type ALL group of patients compared with B-cell type in both periods of chemotherapy., Conclusions: It seems that not only the combination of chemotherapeutic agents but also the cell lineage of ALL are important parameters of altering bone mineral metabolism.

Objectives: Despite advances in conventional treatment, iron-induced cardiomyopathy is still the most frequent cause of death among patients with beta-thalassaemia major. Recent studies have correlated increased myocardial iron content to decreased levels of vitamin D in thalassaemic patients. The aim of this study was to measure parathormone (PTH) and metabolites of vitamin D and consequently to investigate whether these parameters predispose to myocardial iron overload in patients with beta-thalassaemia major., Methods: In 62 patients (29 M and 33 F, mean age: 22.79 +/- 6.18 yr) with beta-thalassaemia major levels of intact parathormone (iPTH) and vitamin D metabolites [25(OmicronH)D(3) and 1,25(OmicronH)(2)D(3)] were measured in serum. Additionally, estimation of myocardial iron content was performed by magnetic resonance imaging, whereas mean serum ferritin concentrations were calculated for 1 yr prior to the study., Results: Results showed markedly decreased levels of serum 25(OH)D(3) in 37 patients (60%), whereas 7 patients (11%) had borderline 25(OH)D(3) levels (between 50 and 75 nmol/L). Serum iPTH levels were significantly higher in patients having increased myocardial iron compared to those having normal myocardial iron (44.04 +/- 22.09 pg/mL vs. 31.39 +/- 14.30 pg/mL, P = 0.017). Multivariant regression analysis identified PTH levels as the major predictor of increased myocardial iron.

The aim of this study was to provide reference standards for measurements of quantitative ultrasonography (QUS) of radius and tibia in normative Greek pediatric population. Analysis was performed in 1549 healthy subjects (814 girls and 735 boys) with a mean decimal age of 11.41+/-3.52 yr (range: 3.78-18.33 yr). Results showed a gradual increase of absolute values of radial and tibial speed of sound (SOS), with aging and with pubertal progressing, in both girls and boys. Gender comparison showed significantly increased SOS values measured both at radius and at tibia in girls more than 13 yr of age compared with aged-matched boys. Significant but mild correlation was noted between standard deviation scores (SDS) of SOS at radius and at tibia (r = 0.259, p < 0.001). Additionally, tibial SOS SDS were significantly negatively correlated with body mass index (BMI) SDS (r = -0.230, p < 0.001). Finally, subjects that spend more than 3h of daily "screen time" (television and personal computer) showed significantly decreased SOS values measured both at radius and at tibia. On the contrary, no correlation was observed between SOS values and the amount of physical activity reported.

Objectives: This study was conducted to assess the role of pelvic ultrasound variables in discriminating between normal girls and girls with different forms of sexual precocity, and to establish reliable cut-off limits of pelvic ultrasound measurements for differentiating between these conditions., Methods: Eighty-eight girls with different forms of sexual precocity (23 with premature thelarche, 15 with premature pubarche and 50 with central precocious puberty) were enrolled. All diagnoses were based on clinical examination with confirmation using the gonadotropin-releasing hormone-stimulation test. Additionally, 81 prepubertal girls, aged 0-10 years, were included as a control group. For statistical analysis and to facilitate comparisons, the groups were subdivided by age intervals (0-6, > 6-8 and > 8-10 years). All subjects underwent pelvic ultrasound examination for the measurement of uterine length, uterine volume, ovarian volume and the anteroposterior diameter at the fundus divided by the anteroposterior diameter at the cervix (fundal/cervical ratio, (F/C)). Finally, the morphological appearance of the ovaries was assessed., Results: Patients with central precocious puberty had significantly higher values for all the ultrasound variables (with the exception of uterine length in the 1-6-year age group) in comparison to normal girls. Patients with premature thelarche and patients with premature pubarche showed similar pelvic ultrasound parameters to those of normal girls. Ovarian volume was the best parameter for identifying patients with central precocious puberty (a cut-off of 3.04 cm(3) had a sensitivity of 100% and a specificity of 97.1% for age interval 0-6 years, a cut-off of 3.35 cm(3) had a sensitivity of 100% and a specificity of 89.5% for age interval > 6-8 years, and a cut-off of 4.46 cm(3) had a sensitivity of 80.8% and a specificity of 88.5% for age interval > 8-10 years). Uterine length was the best parameter for distinguishing between patients with central precocious puberty and patients with premature thelarche (a cut-off of 3.185 cm had a sensitivity of 85.7% and a specificity of 91.7% for age interval 0-6 years, and a cut-off of 3.83 cm had a sensitivity of 82.4% and a specificity of 90.9% for age interval > 6-8 years)., Conclusions: Ultrasound examination of the uterus and ovaries could serve as a complementary tool for the diagnosis of central precocious puberty and, consequently, for the early initiation of appropriate treatment., ((c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)

Purpose: To provide normal references of sonographic uterine and ovarian size in girls aged 1-12 years., Method: Ninety-nine girls were enrolled in the study (mean age +/- SD, 6.9 +/- 2.4 years [range, 1-12 years]). Pubertal status was classified according to Tanner staging, whereas for height and weight assessment a standard stadiometer and weight scale were employed. All subjects underwent pelvic sonographic examination for the measurement of uterine length, volume, ratio of anteroposterior diameter at the fundus divided by the anteroposterior diameter at the cervix (fundal-cervical [F/C] ratio), and ovarian volume and morphology., Results: A gradual increase with age was observed in all uterine and ovarian measurements. Cubic model analysis provided the best curve estimation for uterine length, uterine volume, and ovarian volume in relation to age. Uterine length, uterine volume, ovarian volume and F/C ratio were significantly correlated to both age and height. With respect to ovarian morphology, there was a gradual decrease in frequency of the homogeneous and the paucicystic appearances with increasing age. The macrocystic appearance was observed after the age of 6 years, and its frequency increased gradually with age., Conclusion: There is a continuous increase in size of internal female genitalia from early childhood until the onset of puberty. We have provided reference percentile charts of normal uterine length, uterine volume, and ovarian volume in girls aged 1-12 years., ((c) 2008 Wiley Periodicals, Inc.)

Background: Thalassaemic patients are in need of frequent assessment of bone age because of growth failure and pubertal disorders., Objective: To compare the "rapid" Greulich and Pyle (G&P) method with the third edition of the Tanner and Whitehouse (TW3) method for determining skeletal maturity and predicting final height in thalassaemic patients., Materials and Methods: A total of 191 radiographs from 58 patients (28 male, 30 female) were retrospectively evaluated by two investigators, one for each method. In 47 radiographs from 15 patients having attained their adult height, predicted final height was calculated according to each method., Results: The mean bone ages determined by both the G&P and TW3 methods were lower than mean chronological age, although the differences were not statistically significant (10.04 +/- 3.69 years and 9.98 +/- 3.39 years vs. 10.78 +/- 3.96 years, respectively). Both methods had a tendency to over-estimate final height. Overall, the TW3 method seemed to be more accurate than the G&P method (mean absolute error 3.21 +/- 2.51 years vs. 3.99 +/- 2.99 years, respectively, P=0.048)., Conclusions: The same method should be used when serial assessments are performed, as both methods provide similarly reliable, although not equivalent, results. The TW3 height prediction method seemed to be more accurate in patients with beta-thalassaemia major than the G&P method, albeit with a large confidence interval.

Objective: Osteopenia/osteoporosis of multi-factorial pathogenetic mechanism is reported to be a significant cause of morbidity in adult patients with beta-thalassaemia major. Even in young patients, decreased Bone Mineral Density (BMD) values are a consistent finding in the literature. This study was performed in order to assess BMD in children and young adults with beta-thalassaemia major, regularly transfused and sufficiently chelated, along with auxological, clinical and laboratory parameters., Design: Thirty-five young thalassaemic patients (19 F, 16 M, aged 5-20 yr) were studied. Lumbar BMD was assessed by dual X-ray absorptiometry (DXA) and Z-scores were calculated according to bone density values using age- and sex-matched normal population. None of the patients presented with clinical or laboratory signs of endocrinopathy and none was receiving hormonal replacement therapy., Results: All BMD Z-scores were within normal range, with a mean Z-score of 0.42 for girls and -0.41 for boys (statistically significant gender difference, p=0.018). When correlated with age, a decline in Z-scores was observed, indicating a delay in bone mass acquisition with advancing age in the thalassaemic group compared to controls., Conclusions: Optimal conventional treatment prevents the manifestation of osteopenia/osteoporosis during the first two decades of life in patients with beta-thalassaemia major. However, close surveillance with regular screening, preventive intervention and early management of possible endocrine complications are essential in order to secure normal bone health during adulthood and improve quality of life in the thalassaemic population.

Klinefelter's syndrome (KS) is associated with a wide spectrum of clinical features, such as tall stature, eunuchoid proportions, testes disproportionately small for the level of pubertal development, gynecomastia and behavioral problems. The association of KS with thalassemia intermedia has not been previously reported. A male patient with thalassemia intermedia was diagnosed with KS at the age of 14 years when endocrine evaluation for delayed puberty showed hypergonadotrophic hypogonadism. Thyroid function was normal; however, basal and GnRH-stimulated gonadotropin concentrations were raised while serum testosterone was low. Karyotype analysis revealed KS (47,XXY). Testosterone replacement therapy started soon after diagnosis and now at the age of 20 years the patient's height is 178.3 cm, the U/L ratio is 0.91. Testicular volume is 12 ml (Prader orchidometer) and his pubic hair is stage 4. To our knowledge this is the first case of a patient suffering from KS and thalassemia intermedia reported in the literature.

A case of Angelman syndrome (AS) with thelarche variant in a 4.5-year-old girl is presented. Clinical suspicion of AS was raised at the age of 15 months when she presented with mental retardation and epilepsy, absence of speech, ataxic gait with jerky movements, hyperactivity and paroxysmal episodes of laughter. Moreover, she had facial dysmorphic features such as microbrachycephaly, mid-facial hypoplasia, macrostomia and prominent mandible. Dinucleotide repeat polymorphism (DNRP) analysis, identified absence of maternal alleles at D15S543, D15S113 and GABRB3 loci, findings consistent with AS. Studies on CYP19 locus (outside the 15q11-13 region) revealed the presence of two different alleles, thus excluding the possibility of paternal isodisomy of chromosome 15 in this patient. Breast development at the age of 4.5 years, accompanied by accelerated growth velocity and bone age suggested the diagnosis of variant thelarche. This is the second case of AS with sexual precocity reported and whether this combination is a coincidence or not remains to be clarified.

Moyamoya disease (M-M) is characterized by progressive obstruction of the supraclinoid portion of internal carotid arteries and the proximal middle, anterior and posterior cerebral arteries, associated with the formation of a characteristic net of collateral vessels in the basal ganglia region. Clinical manifestations in childhood include transient ischaemic attacks, seizures and multiple infarcts. Approximately 7% of M-M cases are familial. We report two affected Greek siblings with typical clinical and neuroradiological findings of M-M. Linkage analysis of the whole family was consistent with linkage to the region 3p24-26, as previously reported in other familial Japanese M-M cases.

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria with a slowly progressive course regarding CNS involvement. We present a 13.5-year-old female patient who presented at the Emergency Department with a generalized status epilepticus, which promptly responded to intravenous phenytoin. CT and MRI demonstrated subcortical white matter alterations. The neurological examination revealed mild mental retardation, macrocephaly and ataxic gait with cerebellar signs. Repeated urinary organic acid analysis demonstrated increased excretion of 2-hydroxyglutaric acid which was of the L-configuration. The constellation of macrocephaly in a patient with mental retardation, cerebellar tract involvement and subcortical white matter signal alterations on MRI should alert the physician to the possibility of L-2-HGA. Although rare, epileptic seizures or even status epilepticus can be among the presenting symptoms in organic acidurias with a slow course, such as L-2-HGA.

We report clinical and laboratory data from 32 children with benign acute childhood myositis (BACM), children who presented with calf tenderness and gait abnormality. Laboratory evidence of a viral infection was evident in 23 patients, while serum creatine phosphokinase was uniformly increased (558 to 6800 U/L). Twenty-five patients (78.1%) were given a diagnosis other than BACM by their general practitioner or paediatrician. All patients made a rapid recovery within one week. We conclude that BACM should be encountered among the main causes of sudden-onset gait abnormality in young children.

We report atypical and variable clinical presentation of glutaric aciduria type I (GA I) in four children from two Greek families. In one family, a boy with typical biochemical and neuroradiological features of GA I suffered a metabolic crisis at 16 months of age resulting in a severe movement disorder. His sister, two years older and showing identical biochemical features, has remained neurologically normal throughout childhood and at six years of age is attending normal primary school. Both children are homozygous for P217 L, a novel mis-sense mutation in exon 7 of the glutaryl-CoA dehydrogenase (GCDH) gene. In the other family, monozygotic twins presented at 6 years of age with mild developmental delay and a single episode of hypoglycaemia. Cranial magnetic resonance imaging (MRI) scans in both twins revealed almost identical high-signal alterations in the periventricular white matter and in the centrum semiovale. Biochemical analyses showed massive urinary excretion of glutaric and 3-hydroxyglutaric acids and carnitine depletion. Molecular studies showed compound heterozygosity for two novel putative null mutations, IVS6-1 G > A and Y413 X, in the GCDH gene. The milder clinical course of GA I in three of the four Greek patients demonstrates the phenotypic heterogeneity of the disease even within families. Asymptomatic siblings of GA I patients should always be investigated, and molecular studies may be useful for confirming the diagnosis, particularly when the presentation is atypical.

The effect of one year recombinant human growth hormone (rhGH) treatment on growth rate and bone age was studied in ten short prepubertal children with beta-thalassemia major (age range 7.10-12.03 yr) with normal GH response to provocative stimuli. rhGH was given subcutaneously every day in a dose of 28 IU/m2/week. In the 10 children who completed 12 months of treatment the growth velocity increased from 4.22+/-0.81 cm/yr (-1.38+/-0.80 SDS for CA) to 7.61+/-1.16 cm/yr (+2.27+/-1.64 SDS for CA). IGF-I was low before treatment, 138.3 +/-38.9 ng/ml, and rose significantly to 232.2+/-122.1, 243.2+/-98.4 and 227.5+/-86.2 at 3, 6 and 12 months post-treatment, respectively (p<0.01). Bone maturation was accelerated in proportion to the increase in chronological age. The mean pre-treatment bone age in the ten children was 8.20+/-1.97 and increased to 9.55+/-1.80 yr after one year of treatment. Our data demonstrate that GH treatment of thalassemic children with normal GH reserve and low serum IGF-I concentrations with supraphysiological doses of rhGH for one year can cause a significant increase in serum IGF-I levels and growth velocity, but it remains to be elucidated whether long-term administration will affect the final height.

Unlabelled: Growth hormone (GH) secretion was determined by evaluating circadian GH profiles for 24 h and GH responses to clonidine stimulation test and insulin-stimulated hypoglycaemia (ITT), in nine prepubertal children with beta-thalassaemia major (TM) and 17 with non-GH deficient short stature (NGHDSS). The TM children were multitransfused and had early and intensive chelation therapy. All patients had normal hypoglycaemia to ITT, with peak GH levels of 15.71 +/- 5.86 ng/ml for children with NGHDSS and 13.91 +/- 7.20 ng/ml for children with TM. Peak GH levels during a clonidine test were 17.54 +/- 5.30 and 17.15 +/- 1.38 ng/ml, respectively. The GH peak parameters such as the number of peaks, the integrated GH concentration and the area under the curve (AUC) were similar in both groups of children and reflected the total 24-h secretion and the daily and nocturnal secretion separately. An abnormal 24-h GH profile compatible with the diagnosis of endogenous neurosecretory GH dysfunction was found in only two out of nine children with TM and in four out of seven children with NGHDSS., Conclusion: Our data suggest that growth hormone neurosecretory dysfunction is not a universal finding in children with thalassaemia major but might depend on the degree of iron deposit in the pituitary.