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We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7+/-3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty-nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH-deficient girls (GH peaks8 microg/l after pharmacological tests) and both groups were lower (p0.0001 and p0.0005, respectively) than MGHCs of 27 short normal girls (GH peak8 microg/l). MGHC of the patients with TS was negatively correlated (p0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE20% was significantly higher (p0.02) than that of the TS patients with BWE20%, but again did not differ from that of the GH-deficient patients and was lower (p0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty-four percent of the TS patients showed GH responses to pharmacological tests8 microg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH-deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment.

Objective To trace growth charts for height, weight and body mass index (BMI) that apply to the whole Italian population. Different charts were drawn for central-north and south Italy since children in central-north regions are known to be taller and leaner. Design: Cross-sectional study. Setting: A sample of schoolchildren covering 16 of the 20 Italian regions, with data collected between 1994 and 2000. Subjects: A total of 27 421 girls and 27 374 boys, aged 6–20 y. Methods: Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP references are presented both as centiles and as LMS curves for the calculation of standard deviation scores. According to International Obesity Task Force, SIEDP charts for BMI include the limits for overweight and obesity, ie the centiles having, at 18 y of age, the value of 25 and 30 kg/m2, respectively. Results: The comparison between SIEDP and Tanner et al's charts for height, still in use among most Italian paediatricians, shows that before puberty Italian children are 2–4 cm taller than their English peers. Because of these differences, Tanner's charts fail to detect, when applied to Italian children, 50–90% of short children aged 6–11 y, ie with stature below the 3rd centile of their reference population. Rolland-Cachera et al's centiles for BMI are lower than those of SIEDP standards, mainly during adolescence (up to 6.6 kg/m2 for the 97th centile), and apply poorly to Italian children. The prevalence of overweight is 27 (boys) and 19% (girls) in south Italy vs 17 (boys) and 10% (girls) in central-north Italy. Conclusions: These references intend to supply Italian paediatricians with a tool that avoids the use of outdated or inadequate charts, and thus should be suitable for monitoring their patients' growth. Sponsorship: Italian Society for Pediatric Endocrinology and Diabetes (SIEDP).

AIM—To compare final height in two groups of low birth weight children examined for short stature: the first group untreated because of normal growth hormone (GH) secretion, the second treated with human growth hormone (hGH) because of abnormal secretion. METHODS—A total of 49 subjects born at term of birth weight below the 10th centile were consecutively examined for idiopathic short stature. The first group of subjects (n = 20) with normal GH peaks after pharmacological tests (>8 µg/l) spontaneously reached final height. The second group (n = 29) with abnormal secretion were treated with hGH (20 U/m2/week) for 36-84 months. At diagnosis the two groups were of similar height for chronological age and bone age, and had similar target height. RESULTS—In both groups final height was significantly lower than target height (−0.65 (SEM 0.20) in untreated cases, −0.61 (0.18) in treated cases). Fewer than one third of subjects had a final height above target height. Final height data of untreated and treated cases were not different. In the treated group the best results were obtained by those subjects who improved their height for bone age after three years of therapy. CONCLUSIONS—Our subjects with birth weight below the 10th centile remained as short adults with final height below target height. Treatment with hGH 20 U/m2/week in those diagnosed as deficient was not effective, with final results overlapping those of untreated subjects.

OBJECTIVES We have genotyped the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency identified from March 1980 to December 1997 through a combined program of neonatal screening and case survey in the Emilia–Romagna Region (Italy). We have also analysed retrospectively the possible advantages of genotypical neonatal classification. DESIGN A ‘phase A’ of screening and clinical monitoring (March 1980–September 1983 and March 1991–December 1997) and a ‘phase B’ of clinical monitoring only (October 1983–February 1991) were taken into account. PATIENTS A total of 61 patients (20 salt wasting, nine simple virilizing and 32 nonclassical forms) were genotyped, HLA typed and hormonally tested to understand better the genotype/phenotype relationship and the epidemiology and geographical distribution of associated mutations. The fully genotyped patients were classified into four mutation groups according to the degree of enzymatic activity (‘null’ and ‘A’ to ‘C’). RESULT The most frequent genotype alterations were deletion (24.1% classical, 3.3% nonclassical forms), large gene conversion (9.2% classical, 1.7% nonclassical forms), In2 splice (27.7% classical, 15.0% nonclassical forms), I172N (5.5% classical, 10.0% nonclassical forms), V281L (3.7% classical, 43.3% nonclassical forms), P453S (5.0% nonclassical forms). A significant difference (χ2 = 5.101; P

The aim of this study was to evaluate the role of inhibin B and the determination of its concentration to diagnose testicular damage after treatment for a childhood malignancy. Thirty-seven males treated for Hodgkin disease (n=11) or non-Hodgkin lymphoma (n=26) were examined at a mean age of 16.9 ± 2.9 years. Mean age at the stop of therapy was 11.3 ± 3.0 years and in most cases the chemotherapy regimen included gonadal damaging alkylating agents. Thirty-three normal males (mean age 17.9 ± 4.1 years) were examined as controls. Serum samples were collected for determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Median inhibin values were significantly lower in patients than in controls (96.0 vs 225.0 pg/ml, P

OBJECTIVE Birth weight influences both postnatal growth and the initial response to GH therapy in GH-deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA). DESIGN Retrospective study. PATIENTS 108 GH-treated patients (age at diagnosis 11.1 ± 2.0 years) affected by idiopathic and isolated GH deficiency (peak

The preferential association between Turner's syndrome and congenital heart defects (CHD) have been well known since the first description by Morgagni. There are few studies about the different cardiologic problems stemming from different chromosomal patterns of X monosomies. We reviewed a large series of 136 patients with Turner syndrome without cardiologic preselection, 29 of whom had some kind of CHD (21.5%). Partial anomalous pulmonary venous drainage (PAPVD; 2.9%), aortic valve disease (stenosis and/or incompetence) (AoVD; 5. 1%), aortic coarctation (AoCo; 4.4%), and bicuspid aortic valve (BicAo; 14.7%) are much more frequent in Turner's syndrome than in the normal population, with the difference being statistically highly significant. In our cases, only the 45, X subjects showed severe CHD and multiple lesions, whereas the X-ring pattern was associated with an elevated prevalence of BicAo. Patients with X-deletion showed no signs of congenital heart malformations. Eleven patients, all with 45, X pattern, and significant CHD, underwent cardiac surgery at a mean age of 7.7 +/- 5.3 years (range 7 days-18 years) without complications. At follow-up of 3-18 years (8.6 +/- 5. 2), we were unable to observe any type of evolution of the remaining untreated cardiovascular anomalies.

Urinary growth hormone was measured in 54 children with short stature who had growth hormone deficiency that was initially diagnosed pharmacologically (arginine and L-dopa) and physiologically (mean growth hormone concentration during sleep evaluated twice). Based on the growth hormone response to pharmacological tests the subjects were subdivided into three groups: group A, 20 subjects with normal response (peak concentration > 8 micrograms/l); group B, 20 subjects with response between 4 and 8 micrograms/l; and group C, 14 subjects with response < 4 micrograms/l. In group A four subjects had an abnormally low nocturnal mean growth hormone concentration (< or = 3.3 micrograms/l). In group C seven subjects had multiple pituitary hormone deficiency and abnormal magnetic resonance imaging. All subjects had urine collected from 8.00 pm to 8.00 am for 4-5 consecutive nights. A positive correlation was found between serum nocturnal mean growth hormone values and urinary growth hormone in all subjects. Mean (SD) concentrations of urinary growth hormone were similar in groups A (18.0 (9.5) ng/g creatinine) and B (13.6 (5.9) ng/g creatinine), but significantly higher than that of group C (3.4 (3.7) ng/g creatinine). Considering as abnormal urinary growth hormones below the lower limit of the range in group A, specificity and sensitivity of urinary growth hormone was 100% and 35% respectively. Sensitivity for groups B and C were 5% and 78% respectively. When considering only the subjects of group C with pathological magnetic resonance findings, sensitivity increased to 100%. In the four subjects of group A with mean growth hormone concentration < or = 3.3 micrograms/l, specificity decreased to 80%. It is concluded that urinary growth hormone assay is characterised by a sensitivity too low to be regarded as improving the traditional diagnostic approach to define growth hormone deficiency, unless it is used to identify subjects with the most severe deficiencies.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.Antithyroid antibodies, thyroiditis, thyroid hormones, thyroid ultrasound, Turner's syndrome G Radetti, Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler 5, 39100 Bolzano, Italy

Introduction: We investigated the frequency and types of congenital malformations in infants with congenital hypothyroidism (CH) detected by neonatal screening in four northeastern regions of Italy. Methods: Newborn dried blood specimens were collected at 3–7 days of age. Thyroid hormone (T4) and thyroid stimulating hormone (TSH) were measured by radio-immunoassay. Results: 235 infants with CH were identified among 745 801 screened infants (1:3174). 22 infants (9.4%) had congenital anomalies, as compared to an incidence of 1.8% for congenital anomalies in the general population. The infants with CH and congenital anomalies had significantly lower values for blood T4, birth weight and gestational age. Discussion: This study confirms other data indicating that congenital malformations are substantially more frequent among infants with CH than expected. The presence of these malformations, which often produce clinical complications in the neonate, should not delay collection of the neonatal screening specimen or the start of treatment in infants found to have CH.

Survival of children with acute lymphoblastic leukaemia (ALL) has increased considerably in recent years and data on the spontaneous growth and final height of these children are conflicting. Therefore, we analysed the longitudinal growth and final height in 52 survivors (33 females, 19 males) of childhood ALL. These children were diagnosed and treated in a single institution, all remained in first remission and were submitted to cranial irradiation with either 2400 or 1800 cGy. None of the patients received testicular or spinal irradiation. Median age at diagnosis was 4.2 (range 1.3–9.6) years in the first group (2400 cGy) and 3.9 (0.8–10.5) years in the second (1800 cGy). Standing height was measured at diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24 months after the end of treatment, and finally at the completion of growth. In girls a significant decrease of mean height standard deviation score (SDS) during treatment and a catch up in growth after the end of therapy was followed by a second period of reduced growth. Mean final height SDS was significantly lower than the value at diagnosis in both groups of girls, but only in males treated with 2400 cGy. Mean overall loss in height SDS from diagnosis to final heigth was higher in females (−1.24) than in males (−0.40) (P=0.009). Females 4 years. An unchanged or improved final height was evident in 8 cases, the other 44 cases showed a final height decrease between −0.1 and −2 SDS in 36 and >-2 SDS in 8, 6 of whom were females 4 years. Only females treated at a younger age showed a final height lower than midparental height (−5.7±1.8 cm,P

In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.

Serum growth hormone (GH), insulin-like growth factor (IGF-I), insulin and C-peptide were measured by RIA in fetal blood collected in utero by umbilical cord puncture performed for a variety of indications. Eighty-four fetuses were aged 19-25 weeks and 14 were 26-37 weeks. IGF-I values were lower than the sensitivity of the method. The range for GH was 3-197 micrograms/l (GH-micrograms/l x 2 = mU/l), for insulin 14.3-117 pmol/l, for C-peptide 66.2-827.5 pmol/l. GH significantly increased from week 19 to 25; insulin and C-peptide levels increased from week 19 to 37. GH levels at 19-25 weeks were significantly higher in fetuses with femoral length less than the 5th compared with those with femoral length greater than the 95th centile for that age. GH and insulin levels did not correlate with weight at birth or with maternal hormone levels. These data provide evidence for a presence in living fetuses, from the 19th week, of high levels of GH and of insulin levels not very different from those in adults but these hormones do not seem to be directly responsible for fetal growth.

Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmann's syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms.

Urinary albumin excretion (UAE) was determined by radioimmunoassay in two 24 h urine collections from 125 diabetic children and adolescents and from 71 normal children matched for age and sex. Thirteen patients (10.4%) aged greater than 12 years had microalbuminuria, i.e. log transformed UAE levels above the upper normal range (24.5 mg/24 h). UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. Diabetic normoalbuminuric children aged 10 years and older had significantly higher UAE than controls and than younger diabetic patients matched for duration of disease. HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. All microalbuminuric subjects (n = 8) with short duration of disease (3.92 +/- 3.43 yr) developed diabetes at puberty. In conclusion, our cross-sectional study suggests: if a number of factors are combined, i.e. HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase.

BACKGROUND: Recently a link between hyperhomocysteinemia [HH(e)] and diabetic micro- and macrovascular complications has been reported. However, it is far from clear whether HH(e) is an epiphenomenon or a cause of angiopathic complications. OBJECTIVE: To try to clarify this question we studied adolescents and young diabetic patients without or with only initial complications. SUBJECTS: Plasma levels of basal homocysteinemia [H(e)], folate and vitamin B12 were measured in 76 young diabetic patients (age range 13.6-32.2 yr) and 70 normal volunteers matched for sex and age. In 68 diabetic patients and 53 controls we evaluated the levels of homocysteinemia 2 h after a methionine-loading test. METHODS: Total (free + protein bound) plasma H(e) level was measured by HPLC. RESULTS: Basal or post-load HH(e) occurred in 4.1% of diabetic patients and 12.4% of controls (frequencies not statistically different). In diabetic patients plasma homocysteine values were statistically lower than in controls, but this difference was present only in females. The females showed lower homocysteine values and higher folate levels than males only in the diabetic group. We did not find significant differences in H(e) levels between patients with early complications, late complications or without complications of any type. CONCLUSIONS: Considering very young diabetic patients, the risk of hyperhomocysteinemia does not appear to be greater than in normal controls. Furthermore, our data seem to demonstrate that HH(e) is not a preexisting condition in diabetic patients, even in those predisposed to early complications.

BACKGROUND Little is known about minimal retinal lesions occurring in the first months of disease in children with type 1 diabetes mellitus (DM). OBJECTIVE To detect any early retinal change and to evaluate its progression in children diagnosed with type 1 DM. PATIENTS From 1979 to 1997 we examined by fluorescein angiography at diagnosis or within 15 months from the onset of DM 130 young patients with type 1 DM (mean age at diagnosis 10.08 +/- 2.62 yr). In 112 patients follow-up by fluorescein angiography was performed every 1.26 years with a mean of 5.41 fluorescein angiographies/patient. METHODS The stage of retinopathy was graded to detect minimal lesions. We also considered sex, pubertal stage, HLA, family history of DM, disease duration and HbA1c levels. RESULTS At first examination, 14 out of 127 (11%) readable angiographies showed minimal retinal changes. There was no statistically significant difference between the patients with or without lesions for all parameters considered. The 112 patients examined during follow-up were divided as follows: Group A: no retinopathy at first examination; Group A1: no retinopathy during follow-up; Group A2: retinal changes during follow-up; Group B: retinal changes at the first examination. Mean HbA1c value evaluated during the whole follow-up was lower in group A1 than in group A2. HbA1c levels at onset of the disease were significantly different in the three groups: in group A1 it was lower than in group A2 and in group B. CONCLUSIONS The presence of early lesions in the first year of disease in 11% of patients is probably due to the method of examination, which may detect even minimal retinal changes. This may be correlated to the acute metabolic failure present at the onset of disease. The prolonged follow-up seems to demonstrate that the early changes are not necessarily a negative prognostic factor in the evolution of diabetic retinopathy. We confirm that duration of DM and metabolic control are the main factors influencing the course of retinopathy in these young patients. Early fluorescein angiography is not particularly useful in the management of children with DM.

Background It is well known that birth weight is related to later childhood growth and adult height. It can therefore be hypothesized that this relationship exists also for fetal size before birth. Objective To verify whether a child's final height can be predicted by sonographic biometry in utero. Subjects We evaluated in 116 healthy children both ultrasound measurements in utero and postnatal measurements at a mean age of 6.0 +/- 1.4 years. Methods The following fetal ultrasound measurements were obtained: crown-rump length in the first trimester; biparietal diameter, head circumference and femur length in the second and third trimester. Results Midparental height of the children was correlated both with crown-rump length in the first trimester and with femur length (FL) in the second and third trimester. Predicted adult height was correlated both with FL in the second and third trimester, while present height of the child was correlated with FL only at the third trimester. Conclusions FL showed a close relationship with postnatal measurements. For the extreme values of FL, it seems possible to make quite an accurate prediction of the limits of future height. We can reasonably speculate, therefore, that the basis for the future growth of the child can be found in utero.

We review briefly the definition of central precocious puberty (CPP), and discuss early puberty and very early puberty. The association of hypothalamic hamartoma and empty sella with CPP is described. The contribution of new imaging techniques - CT, MRI and ultrasound in the differential diagnosis of CPP is discussed.

Henoch-Schonlein purpura (HSP) is a widespread necrotizing vasculitis affecting small vessels characterized by nonthrombocytopenic purpura. Pulmonary involvement is a rare fatal complication with diffuse alveolar haemorrhage. The objective of this study was to evaluate possible early lung function abnormalities and to establish any relationship with the clinical activity of the disease. Fifteen children with HSP and without clinical or radiological evidence of lung involvement underwent pulmonary function study at the onset of the disease. A sample of 28 subjects matched by age, height, and weight was chosen as a control group. After a mean of 21 months (range 12-43) lung function tests were repeated in 10 of the previously studied children. During the acute phase of the disease the transfer factor for carbon monoxide, measured by steady-state (TL,COss) and single-breath (TL,COsb) methods, was found to be significantly lower in children with HSP than control subjects. There was no significant relationship between pulmonary function tests with symptoms and signs at onset, nor was there any correlation between variables and serum immunoglobulin A (IgA) concentration. In all but two patients, clinical recovery was observed within 6 weeks from the onset of the disease. In one case relapses of purpuric skin lesions were observed during the first 3 months of follow-up. The second case had relapses of purpuric skin lesions and microscopical haematuria during the 12 months following the onset of the disease with characteristic IgA mesangial deposition on renal biopsy. Although the overall mean value of TL,COsb improved from baseline to the second investigation, in both patients the recurrences of clinical signs were associated with a slight impairment of TL,COsb at the second evaluation. These data suggest an early subclinical lung impairment in children with Henoch-Schonlein purpura during the active phase of the disease. The presence of isolated pulmonary function abnormalities was not associated with the subsequent development of lung disease.

OBJECTIVE The aim of this investigation was to evaluate the utility of IGF-I and IGFBP-3 determinations in screening for GH deficiency (GHD) in children previously submitted to treatment for childhood malignancy. PATIENTS AND METHODS We compared the GH responses to two pharmacological tests (arginine and levo-dopa) with the IGF-I and IGFBP-3 levels in 48 patients (29 boys) who had undergone bone marrow transplantation (BMT) (36 patients) or treatment for a solid cranial tumor (12 patients). RESULTS 22 patients (45.8%) showed GHD (i.e. GH peak < 8 ng/ml in both tests), and only three (13.6%) of the GHD patients had concomitant low IGF-I levels (i.e. -2 SD below the normal mean) and only one (4.5%) an abnormal IGFBP-3 value (i.e. -2 SD below the normal mean). Among the 26 children with normal GH secretion, 21 (80.8%) also showed normal IGF-I and IGFBP-3 levels, three (11.5%) had a concomitant low IGF-I value and two (7.7%) a concomitant low IGFBP-3 value. A significant correlation was found between GH secretion and age at diagnosis (r = 0.26, P < 0.05), and between IGF-I and IGFBP-3 (r = 0.52, P < 0.0001), but not between GH and IGF-I or IGFBP-3. Comparing the growth pattern of these patients from diagnosis to the first year after therapy or BMT, we found that while individual height changes did not correlate with the GH peak, a significant correlation was found between height SDS decrease and IGF-I (r = 0.31, P < 0.05) or IGFBP-3 SDS (r = 0.37, P < 0.01). CONCLUSION Our results indicate that the cut-off of -2 SD for IGF-I and IGFBP-3 was insensitive in screening for GHD. A normal value did not exclude a subnormal GH response to provocative tests and therefore although IGF-I and IGFBP-3 levels may be indicators of the growth pattern, they cannot be used alone as a tool for identifying GHD children after treatment for childhood malignancy.

The case of a 17-year-old male with isolated hypersecretion of dehydroepiandrosterone sulphate (DHEAS) is described. Cushing syndrome, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, an androgen producing adrenal tumour, and elevated plasma DHEAS due to an increased renal threshold were excluded. Selective renal vein catheterization confirmed bilateral, isolated adrenal DHEAS hypersecretion. The dexamethasone suppression suggests a functional nature of this alteration. This condition has to be considered in the differential diagnosis of excessive adrenal androgen production in males, or of hirsutism in females.

AIMS—To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS—Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out β thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS—Fetal serum GH concentrations in group A (median 29 µg/l, range 11-92) were significantly higher (P

We present a girl with lax, redundant skin, ectropion, bulbous nose, macrostomia, and absence of mammary glands. To our knowledge, she represents the fourth described case of Barber-Say Syndrome (BSS). BSS and ablepharon macrostomia syndrome (AMS) share common and distinctive clinical manifestations that involve the same structure of the skin and adnexa. We hypothesize that they may derive from a defective regulation of the same gene.

Editor,—Little information is available on the aetiology of primary not transient congenital hypothyroidism due to thyroid malformations. Usually it is considered to be a sporadic disease; however, to date, there are no reliable studies to identify some possible family risk factors for the disease.1 2Therefore between April and September 1996, during therapeutic follow up of affected children, we examined the mothers of 19 consecutive infants with congenital hypothyroidism (group A) screened through our regional newborn screening program (Emilia-Romagna, Italy) and 17 age matched volunteer mothers of unaffected children …

To determine whether beta-cell function could be impaired by the treatment for Wilms' tumour (WT) in childhood. We investigated the insulin secretion of 44 survivors of WT (22 males) with a median off-treatment follow up of 8.3 years (range 1-19.8). All patients had an intravenous glucose tolerance test (IVGTT) (0.5 gm/kg, max 25 g) to determine the first-phase insulin response (FPIR) (sum of the 1- and 3-min insulin concentrations). Median age at the time of the study was 12.7 years (range 4.2-22.7). Eight subjects (7 males) had a FPIR value below the 3rd percentile, and 7 (3 males) above the 97th centile. Among the 22 patients who received radiotherapy. 7 (6 males) showed a FPIR3rd percentile versus only 1 (a male) of the 22 patients who received no radiation (31.8% vs 4.5%; P0.05). Analysis of variance showed that the time elapsed since therapy had a significant role on the development of low FPIR only in males. The 7 patients with an insulin release97th percentile did not show any significant difference compared to subjects with lower insulin values for weight, age at diagnosis, sex, time elapsed since treatment, radiotherapy and chemotherapy protocol.An impaired insulin response is evident in some patients treated for WT in childhood, mainly in male patients who received abdominal radiotherapy and were examined a longer time after therapy. We hypothesize that this decreased insulin release is related to damage due to radiotherapy and therefore a careful follow up is recommended in adulthood in these patients.

The aim of this retrospective study was to verify whether the daily number of insulin injections could have affected metabolic control in 181 unselected diabetic patients (age 0.66-14.75 yr at onset of diabetes) followed in our clinic from the 1970s to the 1990s. They were evaluated regularly since onset of disease for a mean follow-up period of 6.8 years. The factor with the greatest effect on HbA1c levels was the year of disease onset, which was negatively correlated with HbA1c independently of the daily number of injections and disease duration. Disease duration showed an effect on metabolic control only in the first 5 years of disease. Daily insulin injections affected metabolic control above all as regards 1 vs 2 or more injections. Regarding the change in insulin regimen from 2 to 3-4 injections, there was an improvement in metabolic control in patients with HbA1c > 9% and a worsening in those with HbA1c < 7%/ After the first 5 years of the disease HbA1c levels were higher in adolescent patients than in both younger and older patients. In conclusion, increasing the daily number of injections does not seem in itself capable of eliciting marked improvement in metabolic control, as in our young diabetic patients in the last decade. Multiple insulin injection therapy seems to be mostly indicated for patients with poor control and for adolescents.

The aim of the study was to evaluate the immunogenicity of different commercial recombinant-growth hormone preparations. The presence of antibodies to growth hormone was tested in 210 growth hormone-deficient children at 6-month intervals during treatment for 6-66 months. The patients were treated with three preparations (groups A, B and C of 70 cases each) having the authentic growth hormone sequence. Groups A and B received hormone synthesized by the recombinant DNA technique in E. coli, while the group C preparation was produced in a mammalian cell line. The preparations showed poor immunogenicity and antibodies were found as follows : 1.4% in patients of group A (1 case : binding capacity 0.2 mg/l and Ka 3.5 10 7 l M -1 ), 2.8% in patients of group B (2 cases ; case 1 binding capacity 0.7 mg/l and Ka 1.5 10 7 l M -1 ; case binding capacity 0.04 mg/l and Ka of 1.8 10 8 and 6.5 10 1 M -1 ), and 8.5% in group C (6 cases ; binding capacity from 0.4 to less than 0.02 mg/-1, Ka from 1.6 10 7 to 3.8 10 8 M -1 ). Only two patients of group C presented the antibodies in two subsequent examinations ; in the other patients the positivity was found once. In all patients positive samples were found at intervals of 6-24 months after the start of therapy. In all antibody-positive patients growth velocity presented no decrease at the time of antibody detection and was never different to that of negative patients. We conclude that the three commercial preparations examined showed poor immunogenicity without clinical relevance.

In 105 children and adolescents with IDDM, insulin antibodies were detected as a percentage of radiolabelled insulin both at onset of disease and during the first 8 years of treatment. At diagnosis, 29 patients (27%) were insulin autoantibody positive (IAA+). An inverse relationship was found between IAA levels and age at diagnosis. No significant correlation was seen between IAA positivity and HLA antigens, while there was a negative correlation between IAA and C-peptide levels in the second year of the disease. The percentage of insulin antibody (IA) positive patients increased after insulin administration, with a maximum peak between the first and second year of the disease. The IA response to insulin therapy was similar in IAA+ and IAA- patients, while it was greater in younger children. No relationship was found between IA levels and haemoglobin A1c values, daily insulin requirement, HLA and early complications. No difference in either percentage of positivity or IA levels was seen in patients treated continually for the first 5 years of the disease with monocomponent porcine insulin or human insulin. A negative correlation was found between IA and C-peptide levels in the first and second years of the disease. In conclusion, we have shown that, even after many years of disease, neither IAA nor IA, induced in equal measures by current human insulin preparations, have significant effects on the clinical course of the disease.

There is currently a debate about the use of pharmacological and physiological tests to define GH deficiency and predict response to GH therapy. In addition, a good response to therapy has also been described in subjects without GH deficiency. For further information, we reevaluated GH secretion during replacement therapy in a group of children defined as GH deficient and examined response to therapy in the subjects subdivided according to secretion. One hundred eighty four children (113 boys and 71 girls) initially diagnosed with GH deficiency by means of pharmacological (peak < 8 micrograms/L after arginine and L-dopa tests) and physiological tests (mean nocturnal concentration < or = 3.3 micrograms/L during sleep test) underwent the same tests 2.8 +/- 1.1 yr after start of GH therapy. Sixty eight patients were retested 1.5 +/- 0.4 yr after first retesting. At diagnosis 122 subjects had pathological pharmacological and physiological tests (group A), 30 subjects normal sleep test with pathological pharmacological tests (group B), and 32 subjects pathological sleep test with normal pharmacological tests (group C). At diagnosis 140 subjects were prepubertal and 44 pubertal. To evaluate response to therapy in relation to GH secretion at diagnosis and at both retestings, a number of auxological parameters were calculated during treatment. At first retesting, 107 subjects (58.1%) changed initial group of diagnosis, 34 of whom (18.5%) presented normal secretion in both pharmacological and physiological tests (group D). At second retesting, 31 of the 68 subjects reexamined (45.6%) changed first test results, and 33 (48.5%) reverted to the initial group of diagnosis; none of the 6 subjects of group D maintained normal secretion. Although the percentage of normalized subjects was higher in pubertal subjects (36.4%; P = 0.0003) than prepubertal subjects (8.9%), puberty did not prevent a reduction of secretion in some subjects. Response treatment during the first year of therapy was similar in the various groups. GH secretion seems to change in both prepubertal and pubertal children diagnosed with GH deficiency when pharmacological and physiological tests are repeated over time. Moreover, such tests may not represent a reliable tool for predicting response to treatment. GH secretion normalization at retesting may not necessarily represent the end of a transient secretory defect.

Several computed tomographic scan studies have described empty sellae in children with hypothalamic-pituitary disorders. Magnetic resonance imaging, however, is a more precise technique for visualizing the intrasellar content, such as the stalk and pituitary lobes. Using magnetic resonance imaging, we studied 339 children and adolescents (mean age +/- SD, 12.7 +/- 4.5 yr) with possible hypothalamic-pituitary disorders to ascertain the frequency of primary empty sella and examine its relationships with other intrasellar abnormalities, pituitary function, and adverse perinatal events. One hundred and ninety-three patients had isolated GH deficiency, 43 had multiple pituitary hormone deficiency, 10 had diabetes insipidus, 17 had hypogonadotropic hypogonadism, 5 had idiopathic delayed puberty, 47 had precocious puberty, and 24 had other hypothalamic pituitary disorders of hyperfunction. One tenth (10.9%) of the patients (37 cases) had empty sella, with a marked variation of incidences among the disorders listed above. A statistically higher frequency of subjects with empty sellae was found only in patients with multiple pituitary hormone deficiency. Patients with and without empty sellae were not different in regard to age or sex. The incidence of empty sella in the various groups of patients was as follows: isolated GH deficiency, 8.8% (17 cases); multiple pituitary hormone deficiency, 34.9% (15 cases); hypogonadotropic hypogonadism, 5.9% (1 case); idiopathic delayed puberty, 40% (2 cases); and precocious puberty, 4.2% (2 cases). No patients with isolated diabetes insipidus or other hypothalamic-pituitary disorders had empty sellae. In the patients with empty sellae, abnormalities of the stalk or posterior lobe were found in 1 patient with isolated GH deficiency (5.9%), 13 patients with multiple pituitary hormone deficiency (86.7%), and no patients with puberty disorders. Likewise, adverse perinatal events were found only in 1 patient with isolated GH deficiency and 9 patients with multiple pituitary hormone deficiency. These findings suggest that empty sella is not rare in children and adolescents evaluated for hypothalamic-pituitary disorders, particularly if there is multiple pituitary hormone deficiency. Empty sella can be found regardless of abnormalities of the stalk and posterior lobe, and adverse perinatal events do not seem to be the primary etiological factor. Empty sella is usually associated with pituitary hypofunction, but it can be found in patients with hyperfunction of the hypothalamic-pituitary-gonadal axis.

We studied spontaneous growth and pubertal development in 205 girls with Turner's syndrome, aged 1 month to 28.16 years, according to different karyotypes: 45, X (52%), X-mosaicism (12%), X-structural abnormalities (36%). Data on height, weight, height velocity, bone age and pubertal development were collected yearly in a mixed longitudinal and cross-sectional mode. Pelvic ultrasonography was performed in 133 patients, 46 of whom had contact breast thermography. Standards for height and height velocity (1–20 years) showed no differences when compared with other studies. Some differences were found when these data were subdivided by karyotype. In fact, X-mosaicism subjects had a pubertal growth spurt between 8 and 12 years of age. The spurt observed in this group cannot be justified by the more frequent presence of residual ovarian activity alone. It also appears in patients without ovaries and confirms the influence of a genetic factor on the X-chromosome. In spite of this spurt, the greatest final height was reached by 45, X subjects. X-mosaicism girls had more frequent spontaneous breast development linked to a higher percentage of visible ovaries. In this group the age of the first pubertal signs was similar to that of normal subjects and occurred much earlier than in the other groups.

Adrenocortical tumors in children are extremely rare, accounting only for 0.3-0.4% of all neoplasms in this age. Most frequently they secrete hormones, resulting in virilization, Cushing's syndrome or feminization, while the non-functioning ones are unusual. The authors describe 12 cases observed in 13 years (1976-1989), with a mean age of 5 years. 9 cases showed virilization, 4 presented with Cushing's syndrome and in 5 patients an abdominal mass was palpable. One case was affected by Beckwith-Wiedemann's syndrome. I.V. urography was performed in 8 patients, arteriography in 4 and since 1982 all patients were submitted to abdominal sonography and CT scan or MR imaging. Urinary 17-ketosteroids, 17-hydroxycorticoids and serum testosterone and cortisol were tested in all children. Dexamethasone suppression test was performed in 7. All patients were treated with surgery which seems to be the most suitable treatment, while the real effectiveness of treatment by drug therapy with suppressors of steroidogenesis is not confirmed in children. Histopathological examination showed typical features of adenoma in 5 cases, of adenocarcinoma in 4, while three cases revealed border line forms classified as "atypical adenomas". At the moment 10 patients are alive with a follow-up ranging from 18 months to 14 years, while 2 children with adenocarcinoma are dead.

Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment.

The thymus produces humoral factors that induce the proliferation and differentiation of T cells which are responsible for cell-mediated immunity. Experimental data have suggested that this thymic hormone production is modulated by the neuroendocrine network and, in particular, by growth hormone (GH) and thyroid hormones. To study the role played by GH in thymic endocrine activity in humans, the circulating level of one of the best known thymic peptides, i.e. thymulin (Zn-FTS), has been determined, after a washout period of 2 weeks without GH treatment, in GH-deficient children before and after a single injection of GH. The basal thymulin level is consistently lower in GH-deficient children than in healthy age-matched controls. A single injection of GH induces a significant increment of the thymulin level for at least 48 h. Since thymulin activity may also depend on zinc bioavailability, on thyroid hormone turnover and on the eventual presence of thymulin-inhibitory substances, all these aspects have been checked. No supporting evidence regarding the existence of these kinds of interferences in GH-deficient children has been substantiated. A positive correlation has been found between the serum level of insulin-like growth factor I, but not of GH, and thymulin activity. These data suggest that GH may directly or indirectly modulate the thymic endocrine function in humans. Whether and to what extent such a modulation is relevant to the functioning of the immune system remains to be ascertained.

BACKGROUND—There is a debate about the possible progression of idiopathic premature thelarche towards precocious or early puberty. OBJECTIVE—To evaluate height and age at onset of puberty in a group of girls with a history of idiopathic premature thelarche. STUDY DESIGN—The height and age at onset of puberty of 42 girls now over 10 years of age who were diagnosed with isolated premature thelarche before the age of 3 years were evaluated. RESULTS—Menarche was reached before or at 11 years of age in 13.5% of this group of girls. This percentage of early menarche was higher than would be expected from historical controls in the general population, but was consistent with maternal age of menarche. The mean (SD) height of the girls (n = 15) who achieved adult height was 162.9 (6.3) cm, which was slightly higher than the mean (SD) relative midparental height (160.7 (6.7) cm). CONCLUSIONS—Isolated premature thelarche with onset before 3 years of age progresses towards precocious puberty, although this was consistent with the maternal age of menarche. Furthermore, adult height was normal when compared with population norms in all patients.

The cases of chronic hypodipsis and hypernatremia represent a rarity, especially for the pediatric age group, and are mostly reported as “neurogenic” or “essential” hypernatremia. This paper describes a 2 3/12 yr old girl, 3rd child of healthy related parents, born from a spontaneous delivery (B.W.1200 g: 6.A.36 wks) admitted to our Hospital for hyperphagia, obesity (W.E. 40.1%), absence of thirst, intensified sweating and cyanosis of the extremities all of which begun about 9 months before admission. Poliuria was absent, there was no dehydration and blood pressure was normal. She showed tendency to hyperkinetic behaviour and psicomotor development was retarded. Hypernatremia (serum Na concentration up to 167 mEq/l) and serum osnolality up to 353 mOsm/ml were the major findings. The thyroid function tests (TRH) were consistent with secondary hypothyroidism and hyperprolactinemia. Other endocrine studies, and routine tests also for collagen disease resulted normal. Several ADH measurement showed mean levels of about 4 pg/ml and did not change appropriatly for serum osmolality values. Electroencephalographic recordings and cerebral NMR repeated more than once revealed normal results. A physiatric evaluation showed a chronic hypoventilation. At 3 7/12 yrs of age she was admitted in the our pediatric intensive care unit in coma and the data at that time showed a serum Na up to 170 mEq/l and an osmolality of 340 mOsm/ml. Our treatment consisted of the forced intake of 1,500 ml water/daily, hypocaloric diet and periodic oxidation with regular respitary exercises. Treatment with bromocriptine and L-Tiroxine was instituted. Under these regimens, the patient's situation definitely improved.

Abnormalities of the proportions of peripheral blood lymphocyte subpopulations and of immunoglobulin serum levels were found in twenty patients affected by Turner's syndrome. A slight but significantly decreased percentage of circulating T and B cells, and increased percentage of null cells and a decreased in vitro responsiveness of lymphocytes to phytohaemagglutinin, concanavalin A and pokeweed mitogen were found in Turner's syndrome patients. IgG serum level was found significantly decreased in comparison with age-matched fifty-seven normal males and fifty-seven normal females and IgM serum level was intermediate between female and male values; Turner's syndrome patients with monosomy had an IgM serum concentration very close to male values. The derangement of T and B lymphocyte subpopulations, probably related to the aneuploidy, does not seem to be a severe one but it could account for the immunoglobulin abnormalities and for the association of Turner's syndrome with immunological disorders such as autoimmune diseases. The role of X chromosome on IgM serum level is discussed.

Twenty-one prepubertal children of small stature, 10 boys and 11 girls, aged from 4-3 to 12-8 years, were studied. Their height was less than 3rd centile, and during the preceding year all had a growth rate less than 4-5 cm/year. Arginine and L-dopa tests were given, and the release of growth hormone (GH) during monitored sleep was investigated. On the basis of the electroencephalogram and horizontal electro-oculogram, sleep was divided into stages 1-2-3-4 and rapid-eye-movement. All the children had a GH response greater than 8 ng/ml in at least one of the two pharmacological tests, and were therefore accepted as not suffering from GH deficiency. In all 21 children during sleep there was at least one secretory peak with GH greater than 8 ng/ml. Of a total of 46 secretory peaks recorded, 22 (48%) took place during deep, slow sleep (stages 3-4), 10 (22%) during light sleep (stage 2), 10 (22%) during REM sleep, and 4 (8%) during wakening. In 4 patients (19%) no secretory peak was observed during stages 3-4, even though there were peaks at other times. The data (a) show that it is essential to monitor GH throughout the night to ascertain with certainty the presence or absence of physiological secretory peaks of GH; (b) emphasise the rare disagreement between pharmacological and physiological tests; (c) suggest the use of this physiological test for GH secretion in those cases where the insulin test may be hazardous.

Growth of 79 children with diabetes was analysed at diagnosis and again after one to 10.7 years of treatment with insulin. Both sexes were tall at onset, whereas at the last observation boys alone showed significant growth retardation. Height standard deviation score (SDS), however, showed no significant fall either in 32 subjects reassessed after five years of disease or in 18 subjects examined at full stature. Skeletal maturity was not significantly impaired after treatment. Pubertal growth spurt was reduced, especially in girls and in subjects with onset of disease at or around puberty. We found no significant correlation between height and height velocity SDS and glycosylated haemoglobin values or secretion of growth hormone during the arginine test. Somatomedin C values were correlated with height velocity SDS in prepubertal boys. The results of this study suggest that there are interferences in the growth of children with diabetes but that they do not seem to have a significant influence on adult height.

Sixty-seven prepubertal boys with either uni- or bilateral cryptorchidism were treated with LH-RH or its analogue Hoe 766. In all cases the undescended testes were located in the inguinal canal; none had retractile testes. A) 23 boys were given 200 μg LH-RH-6 times daily for 7 days B) 24 boys were given 500 μg LH-RH-2 times daily for 7 days C) 10 boys received 100 μg Hoe 766 every other day at 8 p.m. for a total of 8 insufflations D) 10 boys received 25 μg Hoe 766 every other day at 8 p.m. for a total of 8 insufflations.

14 diabetic boys (five with a family history of diabetes and nine without) and 29 "short normal" boys were studied. A gonadal function test (2.000 IU of hCG i.m. for 3 days and plasma testosterone assay before and after the hCG administration) as well as an LH-RH test (50 microgram i.v.) were carried out. While basal testosterone level turned out to be similar in the two groups of children, it was significantly lower (p less than 0.01) after hCG than the mean value of the control group. This difference was mainly observed in those patients with a family history of diabetes. In the diabetic children, basal LH level was normal and the pituitary LH reserve was lower than in the control group. Both basal FSH level and FSH pituitary reserve were lower than in normal children. These data show that an alteration in the hypothalamus-pituitary-gonadal function is already evident in the diabetic child.

Although it has been experimentally proved that thyroid hormones stimulate beta 2 receptor activity and tissue responsiveness to catecholamines, previous studies have established that asthma and nonspecific bronchial reactivity (NSBR) can worsen if complicated by hyperthyroidism. Our study is an effort toward the analysis of this contradiction. In 20 congenitally hypothyroid children, substitutive opotherapy was completely withdrawn for 1 month, resumed in the original dosage for 2 months, and then increased by 20% from day 91 to day 110. Mean NSBR, expressed in carbachol-related PD20-FEV1 and PD25-V25, was significantly increased by day 30, remained significantly elevated by day 90, and returned to initial values by day 110. These results suggest that thyroid hormones per se in nonasthmatic subjects decrease bronchial reactivity. This observation should be taken into consideration when attempting to explain the worsening condition of asthmatics who became affected with hypothyroidism. Bronchial reactivity appears to be under the control of many factors (including thyroid hormone levels). Once it is altered, a period of time seems necessary to restore the original bronchomotor tone (2 months in our study).

The considerable variation in the reported incidence of congenital adrenal hyperplasia (CAH 1, McKusick 20191) (Childs et al 1956; Prader, 1958; Hubble, 1966; Rosenbloom and Smith, 1966; Hirschfield and Fleshman, 1969; Qazi and Thompson, 1972; Pang et al 1981) may be explained partially by the lack of a valid screening method. To evaluate the true prevalence of CAH, we examined all the newborns in the Emilia Romagna region of Italy during a period of approximately three years. Emilia Romagna is situated in northern Italy and our sample there was of a homogenous Caucasian population. For the screening programme we took advantage of the specimens collected on filter paper for neonatal screening of hypothyroidism and phenylketonuria. For the 17-OH-progesterone assay, the microfilter paper method modified from that of Pang and colleagues (Pang et al., 1977; Cacciari et al1982; Piazzi et al., 1981; Cacciari et al., 1983) was used.

Fibrinolytic response to venous occlusion and other clotting parameters were studied in 34 obese children and 16 controls. The obese children (mean age 9 2/12 years) had a mean overweight of 51.8% +/- 15.6, higher blood glucose and cholesterol levels, and increased baseline and glucose-induced insulinemia. However, baseline ELT did not differ significantly; ELT after 5 min venous occlusion was 203.2 +/- 110.9 min in the obese children and 114.7 +/- 67.9 min in the control group (p less than 0.01) with a mean percent decrease respectively of 14.9% and 29.2%. Poor fibrinolytic responders did not correlate with age, overweight, or metabolic indices. Lower levels of ATIII (p less than 0.01) and no changes in F VIII: C and F VIII: R Ag were also found in the obese. Furthermore, in a larger group of 84 prepubertal obese children (mean age 10 years; mean overweight 48.2%) and in 39 normal prepubertal children (mean age 10 4/12 years) we also studied platelet aggregation capacity according to Breddin. This parameter was altered in a high proportion of the obese children (p less than 0.05). The obese children were also poor fibrinolytic responders, similarly to obese adults, and exhibited early alteration of the clotting balance.

The Authors have evaluated the relationship between the secretion of dehydroepiandrosterone sulfate (DHA-S) by the adrenal glands and by the gonads in a group of prepubertal and pubertal subjects ("short normal"), both males and females. In the male subjects of a hCG test and an ACTH test were performed; in the female subjects only the latter test was carried out. The behavior of DHA-S under basal conditions was also assessed in both sexes and related to bone age and chronological age in the prepubertal period and during the early stages of puberty. Plasma levels of DHA-S in both sexes increase progressively with chronological age and bone age. A negative correlation was found between DHA-S and bone delay (expressed in percent relative to chronological age) in prepubertal subjects, both males and females. A significant increase in DHA-S after hCG stimulation was found both in prepubertal and pubertal boys. After ACTH stimulation DHA-S increased significantly in prepubertal and pubertal males and females; throughout the test no difference was found between prepubertal and pubertal subjects nor between male and female subjects. Our data confirm that DHA-S is produced both by the adrenals and by the testes.