Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

BACKGROUND: Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). METHODS: Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. RESULTS: Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. HISTOLOGY: 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). CONCLUSIONS: GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency.

BACKGROUND: Deletions of the long arm of chromosome X in males are a rare cause of X-linked intellectual disability. Here we describe a patient with an interstitial deletion of the Xq21.1 chromosome. CASE PRESENTATION: In a 15 year boy, showing intellectual disability, short stature, hearing loss and dysmorphic facial features, a deletion at Xq21.1 was identified by array-CGH. This maternally inherited 5.8 Mb rearrangement encompasses 14 genes, including BRWD3 (involved in X-linked intellectual disability), TBX22 (a gene whose alterations have been related to the presence of cleft palate), POU3F4 (mutated in X-linked deafness) and ITM2A (a gene involved in cartilage development). CONCLUSION: Correlation between the clinical findings and the function of gene mapping within the deleted region confirms the causative role of this microrearrangement in our patient and provides new insight into a gene possibly involved in short stature.

Management of breast cancer after Hodgkin's lymphoma and paediatric cancer.

RATIONALE: The risk of women developing a breast cancer (BC) after receiving chest radiotherapy for paediatric cancers and Hodgkin lymphomas is well established. The aim of this study was to assess these patients' clinical characteristics and clinical outcomes. METHODS: The study concerns women with a history of primary neoplasms treated with chest irradiation ± chemotherapy and subsequently diagnosed with BC. RESULTS: We identified 78 women who developed BC (invasive in 68 cases, 87%). They were a median 18 and 38 years of age when their first neoplasm and BC were diagnosed, respectively. Breast-conserving surgery was performed in 39 patients, and 32 underwent breast irradiation. Twenty of the 41 patients (49%) treated with chemotherapy received an anthracycline-containing regimen. The 5- and 11-year event free survival (EFS) and overall survival (OS) rates were 69% and 42%, respectively. Nine patients (12%) developed a third cancer and 18 (23%) a cardiovascular event. Of the 68 women with invasive BC, the first event involved contralateral BC in 55% of cases: time to progression (TTP) rates were 70% and 47% at 5 and 11 years. The 5- and 11-year BC-specific survival rates (BCSS) were 84% and 68%, respectively. CONCLUSIONS: Judging from our experience, survival rates after BC developing in women previously given chest radiotherapy are not dissimilar to those observed in other women with primary BC. Given the far from negligible risk of subsequent cancers and cardiovascular events, it is mandatory to discuss the best choice of treatment for such patients in terms of their chances of cure and quality of life, and also the risks of late sequelae.

Growth hormone receptor gene expression in puberty.

The mechanisms regulating the synergic effect of growth hormone and other hormones during pubertal spurt are not completely clarified. We enrolled 64 females of Caucasian origin and normal height including 22 prepubertal girls, 26 pubertal girls, and 16 adults to evaluate the role of Growth Hormone/Insulin-like growth factor-I axis (GH/IGF-I) during the pubertal period. In these subjects both serum IGF-I and growth hormone binding protein levels, as well as quantitative growth hormone receptor (GHR) gene expression were evaluated in peripheral lymphocytes of all individuals by real-time PCR. Our results showed significantly lower IGF-I levels in women (148±10 ng/ml) and prepubertal girls (166.34±18.85 ng/ml) compared to pubertal girls (441.95±29.42 ng/ml; p<0.0001). Serum GHBP levels were significantly higher in prepubertal (127.02±20.76 ng/ml) compared to pubertal girls (16.63±2.97 ng/ml; p=0.0001) and adult women (19.95±6.65 ng/ml; p=0.0003). We also found higher GHR gene expression levels in pubertal girls [174.73±80.22 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)] compared with other groups of subjects [women: 42.52±7.66 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase); prepubertal girls: 58.45±0.18.12 ag (growth hormone receptor)/5×10(5) ag (glyceraldehyde 3-phosphate dehydrogenase)], but the difference did not reach statistical significance. These results suggest that sexual hormones could positively influence GHR action, during the pubertal period, in a dual mode, that is, increasing GHR mRNA production and reducing GHR cleavage leading to GHBP variations.

Adherence to growth hormone therapy: a practical approach.

BACKGROUND: Early detection of suspected poor adherence to growth hormone (GH) therapy is crucial to achieve normal final height in GH-deficient (GHD) patients. PATIENTS: 106 children (73 M, 33 F) with a median age of 10.47±3.48 years (mean±standard deviation score (SDS)) exhibited short stature (-1.76±0.64 SDS) and a delayed bone age (8.68±3.42 years). Severe GHD was found in 28, while partial GHD was seen in 78 cases, with low IGF-I values. Recombinant human GH was administered by daily subcutaneous injection at a dosage of 21 µg/kg in prepubertal and 25 µg/kg in pubertal patients. RESULTS: Poor adherence was suspected in a number of patients, but clearly demonstrated in only 4 cases with persistent reduced height velocity in spite of a corrected therapeutic regimen. These patients admitted incomplete adherence to GH injections and clinical and anthropometric measurements revealed their poor response to therapy. CONCLUSIONS: To efficaciously improve adherence in GHD patients, it is mandatory to regularly interview patients; a non-aggressive approach might be utilized to ensure effective communication with patients and their parents.

Metabolic parameters and adipokine profile in growth hormone deficient (GHD) children before and after 12-month GH treatment.

It is a common knowledge that GH exhibits a large number of metabolic effects, involving lipid and glucose homeostasis. The aim of the study was to investigate the effect of one year GH therapy on metabolic parameters and adipokines in GH deficient (GHD) children. Sixteen prepubertal children (11 M and 5 F) with complete GHD (age range: 3.4-14.7 years) and 20 (13 M and 7 F) age and sex-matched healthy children (age range: 4.6-12.3 years) were studied. Blood was collected from patients before starting GH therapy (0.025 mg/kg/day) and one year later, and from healthy children to measure adiponectin, leptin, osteoprotegerin, resistin, interleukin (IL)-6, tumor necrosis factor (TNF)-α levels, and other glucose and lipid metabolism parameters. Adiponectin and resistin levels were significantly higher (49980 ng/ml vs. 14790 ng/ml and 11.0 pg/ml vs. 6.3, respectively) in GHD children before GH therapy than in controls. Serum IGF-I levels (p=0.0001) and height SDS (p<0.0001) significantly increased after 12 months' of GH therapy. There was a loss of body fat reflected by a significant decline in tricep (p=0.0003) and subscapular skinfold thickness SDS (p=0.0023). After 12 months, there was a significant rise in insulin (p=0.0052) and leptin levels (p=0.0048) and a significant decrease in resistin (p=0.0312) and TNF-α (p=0.0137). We observed that lipid and glucose metabolisms are only slightly affected in GHD children. Growth hormone replacement therapy affects some factors, such as leptin, resistin and fat mass, suggesting that also in children, GH treatment has a role in the regulation of factors secreted by adipose tissue.

[Psycho-organic diseases in children and adolescents affected by pediatric neoplasms]. / Disturbi psico-organici in bambini e adolescenti affetti da neoplasie pediatriche.

At Pediatric Oncology Centers, psychological intervention and psychotherapy are generally offered to children and adolescents for supporting their adjustment to disease and treatment. The clinical practice, however, point out that cognitive and emotional symptoms, such as psychic distortions, fatigue, anxiety, irritability and depression, are sustained by biological mechanisms connected with disease and treatment and not respondent to psychological consultation and to other psychosocial resources. These manifestations could interfere with treatment or with the long-term adjustment and call for psychopharmacological treatments. Biological factors able to cause these alterations are not yet studied in depth in clinical tradition and scientific literature on the integration of psychological and psychopharmacological intervention in pediatric oncology is still poor. In this paper organic components of psychic and behavioral alterations in the course of disease are illustrated, considering the symptoms, causes and possible remedies in the light of the most recent interdisciplinary views. The main mechanism connected with oncologic treatments - chemotherapy, surgery, radiotherapy - and responsible for psycho-organic alterations in children and adolescent with cancer are also described.

Growth hormone and disease severity in early stage of multiple sclerosis.

Evidence suggests that neurohormones such as GH and IGF-I are involved in the neuroreparative processes in multiple sclerosis (MS). GH and IGF-I blood levels in naïve MS patients with different disease courses were investigated in this study. Serum GH and IGF-I in untreated MS patients (n = 64), healthy controls (HC, n = 62), and patients affected by other neurological diseases (OND, n = 46) were evaluated with a solid-phase-enzyme-labeled-chemiluminescent-immunometric assay. No differences were detected in GH across MS, OND, and HC (MS = 0.87 ± 1.32 ng/mL; OND = 1.66 ± 3.7; and HC = 1.69 ± 3.35; P = 0.858) when considering gender, disease duration, and disease course. However, GH was lower (P = 0.007) in patients with more severe disease (expanded disability scale score, EDSS ≥ 4.0) compared with milder forms (EDSS < 4). IGF-I l did not differ across the 3 groups (P = 0.160), as far as concern disease course, disability, and gender were. Lower IGF-I levels were detected in subjects older than 50 years compared to younger ones for all 3 groups. Lower GH was detected in patients with more severe MS, and age was confirmed as the main factor driving IGF-I levels in all subjects. These findings, relying on the natural course of the disease, could help in shedding lights on the mechanisms involved in autoreparative failure associated with poorer prognosis in MS.

Growth hormone variants: a potential avenue for a better diagnostic characterization of growth hormone deficiency in children.

Human GH (hGH) is a heterogeneous protein hormone consisting of several isoforms. This heterogeneity is the consequence of multiple hGH genes, mRNA splicing, post-translational modifications, and peripheral metabolism, and it represents one important reason for the disparity among GH assay results from different laboratories. However, other factors are involved: a) interference from endogenous GH binding proteins; b) different specificities of anti- GH (monoclonal and polyclonal) antibodies; c) different matrix effects among the calibrators; d) the use of different calibrators. The measurement of GH levels in response to provocative testing is an essential part of the diagnosis of GH deficiency. For this purpose, an accurate, reproducible and universally valid GH measurement would be highly desirable, but, despite a huge number of efforts in clinical biochemistry, this goal remains elusive.

Diagnosis of growth hormone deficiency is affected by calibrators used in GH immunoassays.

Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4±3.1 years), with the clinical characteristics of GHD (height: -2.3±0.5 SDS; height velocity -2.3±1.5 SDS; IGF-I -1.2±0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment.

Aggressive fibromatosis in children: a changing approach.

Desmoid tumor, also known as aggressive fibromatosis (AF), is a rare monoclonal, fibroblastic proliferation arising in musculoaponeurotic structures. AF is a tumor of intermediate malignancy, with a strong potential for local invasiveness and recurrence. The treatment of choice for these tumors has been changing all the time and may involve surgery, radiotherapy and/or systemic approaches. Surgery generally used to be considered the mainstay of treatment for AF, its goal preferably being a microscopically complete resection with histologically free margins. Mutilating surgery or procedures causing significant loss of function and/or chronic symptoms should be avoided. Involvement of surgical margins is probably associated with an increased risk of local recurrence. Postoperative radiotherapy could be used in cases with positive margins after surgery, or to avoid mutilating surgery in cases of inoperable or inaccessible disease. Postoperative radiotherapy has been reported to raise local disease control to a level similar to that of complete resection, but is associated with a relatively high rate of complications. Systemic treatment may be indicated in case of locally-advanced disease. Several risk factors for local recurrence have been investigated and include: young age, large size, presentation as recurrence, girdles or intra-abdominal location, involved surgical margins, and ß-catenin-activating mutations. Recently collected data prompted the suggestion that these tumors warrant a wait-and-see strategy (clinical-radiological observation, without any treatment), since their natural history is often characterized by lengthy periods of stability or even regression, considering to treat only patients with progressing or symptomatic disease.

Growth hormone/IGF-I axis and growth hormone receptor mutations in idiopathic short stature.

BACKGROUND/AIMS: It was hypothesized that some children with idiopathic short stature (ISS) may have partial insensitivity to growth hormone (GH). In this study analysis of the GH/IGF-I axis as well as GH receptor (GHR) gene was done in children with ISS to determine the possible underlying factor(s) to their short stature. METHODS: Forty-eight patients with a diagnosis of ISS were studied; 33 boys and 15 girls aged 13.6 ± 3.7 years. Molecular analysis of the GHR was performed and GH sensitivity was tested by the IGF-I generation test. RESULTS: Basal IGF-I levels were <-2 SD in 22.9%, and 53.5% showed an IGF-I response below 40% (0-38%) to GH stimulation. GH-binding protein (GHBP) levels were below the normative mean in almost all patients. Mutations in the region of the GHR gene that codes for the extracellular domain of the receptor were found in 15.5%; one newly described mutation was recorded. CONCLUSION: With the possible exception of the novel G62V mutation, functional studies of the other 2 heterozygous mutations found in 6 of our patients are needed in order to prove their impact on short stature.

Efficacy of long-term growth hormone therapy in short children with reduced growth hormone biological activity.

AIM: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. METHODS: In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. RESULTS: We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). CONCLUSION: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.

Hyperimmunoglobulinaemia in Babinga Pygmies is present from infancy.

Pygmies, a population characterized by short stature, have high immunoglobulin (Ig) concentrations. In this study, we evaluated Ig levels in Cameroons Babinga Pygmies from infancy to adulthood and the effects of a national health program on these Ig levels. We found that IgG and IgM levels were outside the normal range for Italians of the same age and were comparable to those measured in Babinga Pygmies living in the same region by Siccardi in 1975. In conclusion, the hypergammaglobulinaemia of Babinga Pygmies is already present in infants and is not affected by sanitation improvements, suggesting that it could be partly genetically-determined.

Efficacy of topotecan plus vincristine and doxorubicin in children with recurrent/refractory rhabdomyosarcoma.

BACKGROUND: This study investigates the efficacy and the feasibility of a chemotherapy regimen with topotecan plus vincristine and doxorubicin (TVD) given on an individually tailored basis to patients with refractory/recurrent rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Nine patients received TVD therapy at relapse, and six were assessable for response. RESULTS: All the six patients experienced objective response after two cycles of chemotherapy: one minor response, four partial response, and one complete response. CONCLUSIONS: The value of our study is severely limited by the small number of cases, the single-institutional setting and the individually tailored treatment, but we nonetheless confirmed the feasibility and tolerability of topotecan-based chemotherapy in RMS.

Serum IGF-I and IGFBP-3 reference values from a chemiluminescent assay in normal children and adolescents of hispanic and italian origin: presence of sexual dimorphism in IGF-I values.

Serum IGF-I and IGFBP-3 assays are used to monitor rhGH treatment. Some discrepancies in results obtained by means of different assays have been reported. The aim of this study was to establish normal ranges for circulating IGF-I and IGFBP-3 in children and adolescents of Hispanic and Italian origin. Circulating levels of IGF-I and IGFBP-3 were measured in 169 Hispanic and Italian prepubertal children and 66 adolescents of both sexes, using a chemiluminescent assay. Serum levels of IGF-I and IGFBP-3 increased from early childhood into adolescence. After pubertal peaks of IGF-I and IGFBP-3, slight decreases were observed with increasing age. Furthermore, serum IGF-I levels were significantly higher in girls than in boys, suggesting a sexual dimorphism in serum IGF-I values in late prepuberty and early puberty. Differences in IGF-I and IGFBP-3 absolute values between our study and previous studies suggest the need to establish reference ranges for each ethnic group.

Growth hormone isoforms release in response to physiological and pharmacological stimuli.

Ten healthy subjects used to performing regular physical activity and eight subjects affected by idiopathic isolated GH deficiency (GHD) were enrolled; 22- and 20-kDa GH secretion and its biological activity were evaluated in response to pharmacological stimuli such as arginine, L-dopa or glucagon in GHD children, while the hormonal response to exercise was studied according to Bruce protocol in healthy subjects. We found a significant increase in 22- and 20-kDa GH level in healthy subjects after monitored physical exercise (MPE; basal 0.28+/-0.12 vs 7.37+/-2.08 ng/ml and basal 0.076+/-0.04 vs 0.18+/-0.05 ng/ml, respectively). Furthermore, the 22-kDa/20-kDa ratio significantly increased in children who had undergone MPE and the GH bioactivity basal mean value also increased significantly after exercise (basal 2.86+/-0.76 vs 7.64+/-1.9 ng/ml). The mean value of 22-kDa GH in GHD patients increased significantly following GH pharmacological stimulation (2.78+/-0.63 ng/ml) when compared with mean basal (0.20+/-0.11 ng/ml) value. In the GHD group the basal concentration of 20-kDa GH significantly increased following GH pharmacological stimulation (0.34+/-0.11 vs 0.72+/-0.2 ng/ml); the 22-kDa/20-kDa ratio significantly increased too. Likewise, GH bioactivity in children with GHD increased significantly after pharmacological stimulation test (basal 2.53+/-0.56 vs 7.33+/-1.26 ng/ml). Both GH isoform concentrations and their biological activity are significantly increased in healthy subjects after submaximal exercise protocol and in GHD children after pharmacological stimuli.

[Fluticasone in the therapy of asthmatic children: short-term effects on growth]. / Il fluticasone nella terapia del bambino asmatico: effetti a breve termine sulla crescita.

AIM: Inhaled corticosteroids (ICS), for years used in the therapy of low-moderate bronchial asthma, reduce the rate of asthmatic attack with improved pulmonary functioning and quality of life. Clinical trials have been addressed mainly to study the efficacy rather than the safety of drugs, so that the side effects of these drugs have not yet been accurately defined. Clinical experience shows that growth delay appears in the first months of therapy with ICS. The aim of the study was to evaluate the influence of the therapy with spacer-administered inhaled corticosteroid on short-term auxological development in prepubertal children. METHODS: In a group of children with low asthma, height and weight have been evaluated before and after six months of inhaled therapy with dipropionate fluticasone at a dose of 100 microg per day. RESULTS: Twenty-five patients (19 males and 6 females; age 5.5+/-1.6 years; range: 2.6-7.8 years) showed a regular growth during the six months of therapy (mean height 0.8 standard deviation score [SDS] before therapy and 0.8 SDS after therapy), while 21 (17 males and 4 females; age 10.0+/-1.5 years; range 8.0-12.7 years) showed an increment of growth rate (mean height from 0.5 SDS to 0.7 SDS, respectively). CONCLUSION: Spacer-administered low dose fluticasone does not negatively influence short-term growth rate, regardless of the age of the patients.

Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency.

In this study we investigated 9 prepubertal children with blunted GH response to classic pharmacological stimuli in contrast with normal auxological evaluation. The children were followed to evaluate their growth velocity for a longer period before starting replacement GH therapy. To evaluate the pituitary reserve a supraphysiologic stimulus such as GHRH plus arginine was used. Serum GH levels were measured by a time-resolved immunofluorimetric assay before and after 1 microg/kg body weight iv injection of GHRH, while serum PRL, IGF-I, and insulin were evaluated only in basal conditions using an automatic immunometric assay. Out of 9 studied subjects, 7 underwent GHRH plus arginine administration and showed a normal GH response; the parents of the remaining 2 children refused the test. Normal serum levels of PRL, IGF-I, insulin, and a normal insulin sensitivity were observed in all children. After 1 yr, the growth rate in each patient was further improved and reached almost normal values. Our results further confirm that the decision to start replacement GH therapy should be based on both auxological parameters and laboratory findings. The GHRH plus arginine test appears to be useful to identify false GH deficiency in children showing a blunted GH response to classic stimuli in contrast with normal growth rate.

[Changes in circulating levels of adiponectin and leptin in children during the first two years of life]. / Variazioni dei livelli circolanti di adiponectina e leptina nel bambino nei primi due anni di vita.

AIM: Adiponectin, leptin and insulin play an important role in the control of growth and glyco-metabolic homeostasis both during pre- and post-natal life. In order to find out markers indicative of post-natal growth, we evaluated circulating levels of these growth factors in full term small for gestational age (SGA) children, during the first 2 years of life, correlating them with the auxological parameters. METHODS: Fourteen SGA (8 males and 6 females) and 16 AGA (appropriate for gestional age) infants (7 males and 9 females) have been included in this study, recording length, weight, body mass index (BMI), adiponectin, leptin and insulin levels at birth. In SGA subjects, these biochemical and clinical parameters have also been evaluated at the first and at the second year of age. RESULTS: AGA and SGA adiponectin and insulin levels at birth did not show statistically significant differences, while leptin concentrations were significantly (P=0.011) lower in SGA children (median 418.49, range 157.68-903.67 pg/mL) in comparison with AGA ones (median 811.71, range 312.50-3085.95 pg/mL). CONCLUSIONS: In conclusion, at birth adiponectin and insulin levels do not differ between AGA and SGA subjects while leptin concentrations are significantly lower in SGA infants and positively correlated to the birthweight.