Tumor necrosis factor-alpha levels in short children

Growth hormone has been suggested to modulate the release of cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1). Moreover, TNFalpha synthesis has been shown to be decreased in hypophysectomized rodents. The aim of this study was to evaluate the influence of GH status on TNFalpha levels in a group of 44 short prepubertal children. Among them, 13 children aged 9.8 +/- 3.5 years were growth hormone (GH) deficient and the other 31 short children had normal growth velocity, normal GH response to provocative testing, and did not suffer from any chronic disease, thus this group was diagnosed as having idiopathic short stature (ISS). A group of 40 age- and sex-matched healthy children was used as controls. No significant differences in basal TNFalpha levels (pg/ml) were found between the GH deficient, ISS children and healthy controls. Furthermore, there was no correlation between TNFalpha and basal serum concentrations of GH or peak GH levels after stimulation. Similarly, TNFalpha values did not correlate with either IGF-I or IGFBP-3 serum concentrations.     

Growth of children with β-thalassemia major

Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5–1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.     

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.     

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH RETARDED CHILDREN TREATED WITH GROWTH HORMONE I. Secretion of Growth Hormone and Somatomedin before and after Treatment

Abstract. Kastrup, K. W., Andersen, H., Eskildsen, P. C., Jacobsen, B. B., Krabbe, S. and Petersen, K. E. (Children's Hospital, Fuglebakken and Herlev Hospital, Copenhagen, Denmark). Combined test of hypothalamic—pituitary function in growth retarded children treated with growth hormone. Acta Paediatr Scand, Suppl 277: 9, 1979.—In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/l), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/l). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm to 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.     

Urinary excretion of pyridinium crosslinks in short children treated with growth hormone

The aim of this study was to evaluate the effect of growth hormone (GH) treatment on bone resorption in children with GH deficiency and those with idiopathic short stature. The study population included seven children with subnormal spontaneous GH secretion and 13 children with idiopathic short stature, all of them pre-pubertal. Anthropometric measurements, free, protein-bound and total urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), serum GH, and serum immunoreactive PTH were measured at baseline and months 1, 3, 6 and 12 of GH treatment. The urinary excretion of total Pyd and Dpd, standardized by the cube of height (m3) in overnight, 24-hour urine collections was not different from age-matched healthy controls at baseline in either group of patients. During treatment with human recombinant GH, both pyridinium crosslinks increased above normal values, reaching a peak after one month in children with GH deficiency and later (after 3-6 months) in children with short stature. Free and total crosslink forms were correlated, and GH treatment did not affect the proportion of free to bound crosslinks. Serum concentrations of iPTH showed a moderate but not statistically significant increase. This study provides no evidence of reduced bone resorption in untreated GH deficiency or in idiopathic short stature. GH treatment induced a marked, but temporary, increase of bone resorption in both groups of patients.     

Growth hormone treatment in young children with Down's syndrome: effects on growth and psychomotor development.

BACKGROUND: Learning disability and short stature are cardinal signs of Down's syndrome. Insulin-like growth factor I (IGF-I), regulated by growth hormone (GH) from about 6 months of age, may be involved in brain development. AIMS: To study long term effects of GH on linear growth and psychomotor development in young children with Down's syndrome. Study design-Fifteen children with Down's syndrome were treated with GH for three years from the age of 6 to 9 months (mean, 7.4). Linear growth, psychomotor development, skeletal maturation, serum concentrations of IGF-I and its binding proteins (BPs), and cerebrospinal fluid (CSF) concentrations of IGF-II were studied. RESULTS: The mean height of the study group increased from -1.8 to -0.8 SDS (Swedish standard) during treatment, whereas that of a Down's syndrome control group fell from -1.7 to -2.2 SDS. Growth velocity declined after treatment stopped. Head growth did not accelerate during treatment. No significant difference in mental or gross motor development was found. The low concentrations of serum IGF-I and IGFBP-3 became normal during GH treatment. CONCLUSIONS: GH treatment results in normal growth velocity in Down's syndrome but does not affect head circumference or mental or gross motor development. Growth velocity declines after treatment stops.     

Growth hormone therapy for short stature in Diamond Blackfan anemia

BACKGROUND: We report a 13-year-old male with Diamond Blackfan anemia and short stature. He had a normal biochemical response to growth hormone (GH) stimulation, but his bone age was delayed, his insulin-like growth factor 1 (IGF-1) was low, and he had a poor growth velocity. He was started on daily GH injections. METHODS: From the patient's medical record the following data were collected: serial heights, serial weights, hemoglobin, hematocrit, bone age, IGF-1, and steroid dose. RESULTS: This patient had an increase in growth velocity up to 8.2 cm/year. CONCLUSIONS: Growth hormone therapy should be considered in children with DBA, short stature and poor growth velocity.     

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF-I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

ABSTRACT. Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5–12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

��С��ͯѪ�����������ȵ�������������-1�����������ؼ����ٴ�����

目的探讨血清生长激素(GH)、胰岛素样生长因子-1(IGF-1)及尿GH检测对矮小儿童诊断的意义。方法华中科技大学同济医院儿科于2004-11—2005-06对106例矮小儿童进行垂体功能复合刺激试验,试验前收集所有受试者夜间12h(2000~800)尿。另选取19例正常青春发育期前儿童为对照组。对垂体功能复合刺激试验GH分泌异常的56例矮小儿童,用ELISA方法检测相应的血清GH、IGF-1及尿中GH水平,并进行相关分析。结果根据垂体功能复合刺激试验的GH检测结果将矮小儿分类,包括完全性GH缺乏症(cGHD)25例、部分性GH缺乏症(pGHD)9例和GH神经分泌功能障碍(GHND)22例。GHD组患儿血清IGF-1、尿GH水平与正常儿相比明显降低(P<0·01)。pGHD和GHND组患儿血IGF-1水平波动较大,无统计学差异。GHND组患儿尿GH水平按ng/g肌酐(Cr)计量显著低于正常对照相(P<0·05),而按ng/12h尿量计算值虽低于正常组,但无统计学意义(P>0·05)。pGHD组患儿尿GH水平按两种方法计量值均介于正常和GHD患者之间,与正常及GHD患者比较均有显著性差异(P均<0·05)。cGHD和pGHD组患儿尿GH的ng/gCr计量值与其血GH峰值呈显著性正相关(rcGHD=0·556,P<0·05;rpGHD=0·423,P<0·05),GHND组患儿尿GH的ng/gCr计量值与其血中GH峰值无相关性(P>0·05)。结论尿GH水平测定无创、简便,配合IGF-1等指标的检测,对于矮小儿童的诊断和鉴别诊断具有重要意义。     

Noonan's syndrome: abnormalities of the growth hormone/IGF-I axis and the response to treatment with human biosynthetic growth hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

Empty sella in short children with and without hypothalamic-pituitary abnormalities

A study was conducted on growth hormone (GH) response to oral clonidine (0.15 mg/m²), GH and cortisol responses to i.m. glucagon (0.1 mg/kg), and glucose response to an oral load of glucose (1.75 g/kg). Measurements were made on the circulating concentrations of free thyroxine (FT4), thyroid stimulating hormone (TSH) and different growth parameters and CT sellar images in 25 GH deficient children (Peak GH response to clonidine and glucagon<7 ug/ml), 15 growth retarded children (Ht<5th percentile for age and gender) with sickle cell disease (SCD) and GH deficiency, 30 randomly selected children with normal variant short stature (NVSS) (HtSDS 2SD below the mean for age and gender with normal GH response to stimulation (>10 ug/ml) and 20 age-matched normal children were evaluated. Out of the 25 children with GH deficiency, five had multiple pituitary hormonal deficiency (GH<TSH and/or ACTH. deficiencies), and 20 had isolated GH deficiency. Empty sella, either complete or partial, was detected in 9 out the 20 children with isolated GH deficiency (45%), 4 out of the 5 children with multiple pituitary deficiency (80%), all the children with SCD and GH deficiency (100%), 3 out of the 30 children with NVSS (10%) and in none of the normal children. The insulin-like growth factor-1 (IGF-I) concentrations were significantly lower in the two groups of children with GH deficiency compared to those with NVSS. The height standard deviation scores (HTSDS) were significantly lower and the annual growth velocity was slower in children with idiopathic GH deficiency and empty sella compared to those with NVSS and those with empty sella associated with SCD. The bone age delay (yr) did not differ among the 3 groups of children with short stature. All children with isolated GH deficiency associated with empty sella had normal body mass indices (BMI), while all the children with SCD and empty sella had BMI below the 5th percentile for the corresponding age and gender. None of the children had glucose intolerance. In conclusion, children with growth retardation and abnormal hypothalamic pituitary functions have high incidence of empty sella. However, empty sella is detected in considerable number (10%) of short children with normal hypothalamic pituitary function.     

Neurosecretory Dysfunction of Growth Hormone Secretion in Thalassemia Major

ABSTRACT. The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-relasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion.     

Neurosecretory dysfunction of growth hormone secretion in thalassemia major

The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-releasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion.     

Variations of pulsatile growth hormone release in healthy short prepubertal boys

Overnight growth hormone (GH) concentrations obtained by frequent venous sampling of 20 healthy, short prepubertal boys were evaluated using the objective pulse detection algorithm, CLUSTER. The resulting pulsatile characteristics were compared with those of 11 healthy prepubertal boys of normal stature and with those of nine prepubertal children with documented GH deficiency. Although no significant differences of pulsatile GH release were found between the normal and short subjects, a subset of the short prepubertal boys with significantly delayed skeletal ages had subnormal sum of GH pulse areas and sum of GH pulse amplitudes. The finding of a significant correlation in all subjects between growth velocity and the sum of GH pulse amplitudes is important, as the results are compatible with the hypothesis that alterations of amplitude-modulated GH release underlie the pathophysiology of suboptimal growth in some short prepubertal children.     

Zinc deficiency: a contributing factor of short stature in growth hormone deficient children

Zinc is an essential trace element which affects growth by promoting DNA and RNA synthesis and cell division. Zinc deficiency causes growth retardation and its frequency is high in developing countries. It could contribute to the effect of growth hormone (GH) treatment in GH deficient children. In this study, we investigated zinc deficiency in GH children. Twenty-four GH deficient children (treated with GH for 2.2 +/- 1.6 years) were recruited for the study. Intracellular erythrocyte zinc levels were measured. Eleven (45.9 per cent) were found to be zinc deficient (Group 1), while 13 patients (54.1 per cent) had normal zinc levels (Group 2). The mean growth velocity was 5.98 +/- 0.8 cm/year in Group 1 and 6.9 +/- 1.4 cm/year in Group 2. Group 2 was given oral zinc supplementation with a resultant growth velocity of 7.51 +/- 0.5 cm/year. During GH treatment in GH deficient children, zinc status should be evaluated as severe zinc deficiency could affect the response to GH treatment.     

Growth velocity, growth hormone therapy, and serum concentrations of the amino-terminal propeptide of type III procollagen

The relationship between serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and growth was assessed in 307 healthy subjects and 82 children with disorders of growth (41 with insufficient growth hormone, 23 with short stature and normal endocrinologic studies, 18 with tall stature) by means of a recently developed, simplified PIIINP radioimmunoassay. The PIIINP value appeared to be related to height velocity; in healthy children of each sex, the pattern of change with age mirrored the shape of the standard height velocity curve; in children with disorders of growth, there was a statistical correlation (p less than 0.001) between PIIINP concentration and height velocity. However, measurement of serum PIIINP alone had no diagnostic value because there was considerable overlap of PIIINP values in children with growth hormone insufficiency, short stature, normal stature, and tall stature. The most appropriate application of PIIINP may be in the monitoring of prepubertal children receiving exogenous growth hormone therapy; in these patients, increases in height velocity were reflected by increases in PIIINP, and early increases in PIIINP may have predictive value.     

The efficacy of grwoth hormone in different types of growth failure

One hundred and one children with GH deficiency, prenatal growth disorders, growth-retarding diseases, or normal variant short stature received GH for at least one year. Responders were observed in all groups. In the whole series of 72 prepubertal children the increments in height velocity showed negative correlations with the highest serum GH levels obtained in provocation tests.In the prepubertal children with normal growth potential the velocity SDSs during the first year of therapy showed positive correlations with initial ages and BAs, and negative correlations with height SDSs. In the 5 children with cartilage-hair hypoplasia the mean velocity increased from -1.9 to -0.6 SD. In the 8 children with Mulibrey nanism the mean velocity increased from -2.0 to 0.8 SD. The 4 children with various chromosome anomalies also showed an acceleration.The therapy brought about a significant increase in predicted final height only in the groups with normal growth potential. Final heights were known for 16 patients. Their heights were fairly accurately predicted by the RWT method, but the IPH method gave overpredictions. Both predictions showed strong correlations with the final heights.Additional low-dose androgen therapy in 10 boys, started at ages 9.5 to 18.9 years and after 1.4 to 4.7 years of GH therapy, accelerated growth without substantially affecting predicted height. The acceleration was mostly of the growth of sitting height.Abbreviations BA bone age - CHH cartilage-hair hypoplasia - GHD GH deficiency, GH deficient - iGHD isolated GHD - IPH index of potential height (height SDS for adjusted BA) adult height prediction method [23] - Maximal GH highest plasma GH level during an insulin or insulin-arginine test - MPHD multiple pituitary hormone deficiency - RWT the adult height prediction method of Roche, Wainer and Thissen [39] - SDS height standard deviation score - SDS SDS corrected for parental height     

Effect of zinc supplementation on growth hormone secretion, IGF-I, IGFBP-3, somatomedin generation, alkaline phosphatase, osteocalcin and growth in prepubertal children with idiopathic short stature

Controversy exists about the effect of zinc on growth and the GH-IGF system. Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children. However the mechanism of this effect has not been well characterized. Furthermore, the effect of zinc supplementation on non-zinc-deficient short children is unknown. We investigated the effect of zinc supplementation on endogenous GH secretion, serum IGF-I and IGFBP-3 concentrations, IGF-I and IGFBP-3 generation in response to exogenous GH, bone formation markers, and linear growth of non-zinc-deficient children with idiopathic short stature. We analyzed prospectively serum zinc, IGF-I, IGFBP-3, alkaline phosphatase, osteocalcin, and GH response to clonidine test, and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 (16 M, 6 F) prepubertal children with idiopathic short stature. Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml (p <0.001), IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml (p <0.001), alkaline phosphatase from 525+/-136 to 666+/-197 U/l (p <0.0001), and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml (p <0.05) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation (peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml, GH area under the curve during clonidine test 689+/-395 vs 761+/-468, NS). Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation (118% vs 136% and 57% vs 44%, respectively). There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested. Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months (6-12 months) (-2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS, respectively). Zinc supplementation increased basal IGF-I, IGFBP-3, alkaline phosphatase and osteocalcin without changing GH response to clonidine. Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test. These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3, alkaline phosphatase and osteocalcin. Despite improvements in the above parameters, zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6-12 months follow-up.     

The diagnosis of childhood growth hormone insufficiency and growth hormone resistance

Growth hormone insufficiency (GHI) is an uncommon though treatable cause of retarded growth velocity and short stature in childhood, the diagnosis generally requiring the demonstration of a subnormal growth hormone (GH) response to a physiological or pharmacological stimulus. Physiological and pharmacological GH release is a continuous variable and the relationship between spontaneous GH secretion and height velocity is asymptotic. Cut-off points for defining GH insufficiency are largely derived from adult observations, but have been extrapolated to children, for whom normative data are relatively scanty. There is no absolute cut-off that discriminates between normal and abnormal GH response. Moreover, poor reproducibility, sensitivity and specificity of the many dynamic tests available, particularly when performed in the very young child or in early adolescence, together with the confounding effects of assay performance, further weaken the diagnostic efficiency of biochemical investigations. Between 20-40% of children retested at the completion of GH therapy demonstrate a normal GH response to a provocative stimulus. Such limitations mitigate against over-reliance on GH provocation tests in diagnosis, and further emphasize the importance of careful auxology in evaluating the short child.     

Age related IGF-I changes and IGF-I generation in thalassemia major

We measured serum concentrations of insulin like growth factor-I (IGF-I) in 20 thalassemic males with short stature (height SDS <-2) and/or slow growth velocity (GV <-1 SD) throughout their childhood and adolescence, compared these data with normal reference data validated in our lab, and evaluated their growth hormone secretion in response to clonidine and glucagon stimulation. We also performed IGF-I generation test on 26 patients with beta thalassemia major (BTM) before and after blood transfusion to evaluate the effect of increased hemoglobin (Hb) on IGF-I and its response to GH. We obtained the following results. 1) No statistical difference in age, HSDS, target height SDS or bone age was observed between BTM patients with growth hormone deficiency (GHD) compared to those with normal GH secretion (GHS). 2) The age-related levels in serum total IGF-I in thalassemic males were significantly decreased from early childhood to 18 years of age compared to normal subjects. Thalassemic males with GHD did not show any significant peak of IGF-I levels until 18 years of age, whereas thalassemic males with normal GH response to provocation (GHS) achieved a significant peak level of IGF-I that was attenuated and late compared to normal males. The basal serum IGF-I concentrations at different ages did not differ between the GHD and GHS groups until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS. A significant increase in the circulating basal IGF-I concentrations from 53 +/-35 ug/l to 82.6 +/- 39 ug/L was achieved with increasing Hb concentration after blood transfusion. The serum total IGF-I levels increased significantly with the administration of human growth hormone (hGH) for 4 days, both before and after blood transfusion. The peak IGF-I response to GH injections did not differ before compared to after blood transfusion. The percent increment of IGF-I levels generated after GH injections was higher in thalassemic children with GHD as compared to those with GHS both before and after blood transfusion. In conclusion, our results showed that agerelated serum IGF-I concentrations were significantly lower in short thalassemic patients, with and without GHD, during childhood and adolescence, compared to normal standards. Correction of anemia significantly increased serum concentration of IGF-I but does not affect the increase of IGF-I in response to GH stimulation.