Search

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.

L’industria petrolifera genera elevate quantità di rifiuti solidi e semisolidi, chiamati morchie o fanghi oleosi, classificati come rifiuto pericoloso. La frazione organica di tali rifiuti costituisce da un lato un inquinante ambientale, dall’altro una possibile fonte di idrocarburi di interesse commerciale. L’attività di microrganismi in grado di biodegradare e/o biotrasformare gli idrocarburi alifatici e aromatici potrebbe contribuire a decontaminare questo rifiuto, o a destrutturarlo, favorendo il recupero di idrocarburi ad alto valore aggiunto dallo stesso. Scopo di questo lavoro è stato studiare l’effetto della biomassa microbica indigena e di un inoculo microbico sul destino degli idrocarburi di una morchia in reattori batch aerobici. Lo studio ha evidenziato un aumento progressivo, più rapido in presenza di inoculo microbico, della concentrazione di idrocarburi estraibili dalla morchia, sia alifatici che policiclici aromatici (IPA), aprendo interessanti prospettive di valorizzazione di tali rifiuti.

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

Improvement of MRI diagnostic accuracy in the study of the hypothalamic-pituitary region provides precise anatomic details. In pituitary dwarfism, MRI reveals severe sella/pituitary gland and stalk hypoplasia with or without posterior pituitary ectopia, and empty sella, and this more frequently in patients with multiple pituitary hormone deficiency. Two main hypotheses have been proposed to explain these findings: traumatic stalk transection during breech delivery, and abnormal embryonic development of the pituitary gland. The association between neuroradiological findings and type/severity of endocrine alteration has not yet been clarified. In diabetes insipidus, MRI findings are normal picture, posterior lobe not visible, and thickened stalk (as expression of preclinical/initial histocytosis). Patients with central precocious puberty or hypogonadotropic hypogonadism rarely show morphologic abnormalities (hamartoma of the tuber cinereum, partially empty sella). So far, MRI permits one to identify morphologic pictures in diseases previously considered 'idiopathic'.

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.

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.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.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').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 (chi2 = 5.101; P0.025) in the distribution of classical genotypes was found in Romagna (south-east; incidence 1 : 7437 newborns) compared to Emilia (north-west; incidence 1 : 25 090 newborns). Two putative new mutations were found in our population. Little discrepancy was found between genotype and phenotype.The high frequency of genotypes 'null' or 'A' in the 'phase A' vs. 'phase B' of our study confirms the usefulness of neonatal screening in preventing the death of male patients with salt wasting forms. The substantial similarity in the mutational spectrum of classical forms found in our study, based on the detection of all the classical patients of a specific area, leads us to believe that the distribution of mutations is due to the inherent characteristics of the gene locus, and that regional effects play a minor role. Prompt neonatal genotyping can be of valuable diagnostic assistance in neonatal screening for the confirmation of the diagnosis in newborns with moderately elevated 17 hydroxyprogesterone levels.

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.

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).Retrospective study.108 GH-treated patients (age at diagnosis 11.1 +/- 2.0 years) affected by idiopathic and isolated GH deficiency (peak8 microg/l after pharmacological and/or nocturnal mean GH concentration/= 3.3 microg/l) were examined. Twenty-four had a birth weight3rd centile (2300 g +/- 268 - small for GA), 77 between the 3rd and 90th centile (3216 g +/- 317: appropriate for GA) and 7 above the 90th centile (4193 g +/- 143: large for GA).All subjects reached final height (growth velocity0.5 cm/year in the last year of treatment) after hGH treatment (range 33-96 months) at a dose of 20 U/m2/week. The 3 groups of subjects started therapy at a similar height for chronological and bone age.Final height in the small for GA group was - 1.71 +/- 0.93 standard deviation score (SDS), significantly lower than that of both appropriate (- 1.14 +/- 0.83 (P0.01)) and large (- 0.70 +/- 0.89 (P0.01)) for GA groups. Similarly, the small for GA group had a significantly lower height SDS increment from the start of therapy to adult height (0.54 +/- 0.84) than both the appropriate (0.99 +/- 0.78 (P0.05)) and the large (1.49 +/- 0.84 (P0.01)) for GA groups. The percentage of subjects with final height above target height was significantly different in the 3 groups: 21% for the small, 38% for the appropriate and 71% for the large for GA groups (P0.05). In the whole group of patients there was a positive correlation between birth weight and final height (r = 0.38; P0.0001).The present study showed that our patients, affected by isolated and idiopathic GH deficiency but with different birth weights, despite starting treatment with a similar height and bone age delay, had different auxological outcomes. It seems, therefore, that final height is strongly influenced by birth weight which penalizes the smaller newborns and assists the larger ones.

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.

We report final height data of patients with Turner's syndrome collected by the Italian Study Group for Turner's Syndrome. One hundred and thirty-five patients reached their final height during GH therapy with different therapeutic regimens (dose and combination). They were divided into 3 groups: group A, 74 patients with high doses of GH (1 IU/kg/week) for at least 2 yr; group A1, GH alone and estrogen therapy added not before 14 yr of chronological age (47 patients, of whom 30 were treated for4 yr and 10 for6 yr); group A2, GH plus ethinyl estradiol (17 patients) or GH plus oxandrolone (10 patients); group B, 51 patients with low doses of GH (0.5 IU/kg-week) and high doses of GH for less than 2 yr; and group C, 10 patients with high doses of GH with spontaneous menarche. In contrast to the patients of groups B and C, the patients of group A showed a significantly higher final height (mean, 147.5+/-6.5 cm) than their projected height (mean, 142.9+/-6.4 cm). They showed also a significantly higher final height compared to the subjects of groups B (mean, 145.6+/-5.7 cm) and C (mean, 143.0+/-5.3). Among the patients of group A, the best results were obtained in the patients of group A1 treated with GH alone at high doses and for a longer period (4 yr, 149.3+/-6.4 cm; 6 yr, 153.8+/-4.0 cm). Karyotype, GH secretion, and birth weight did not influence the efficacy of GH therapy. A low target height and a high prevalence of a spontaneous ovarian activity or menarche may negatively influence the effect of GH therapy. Estrogens did not improve final height when added to GH therapy. The use of small doses of oxandrolone was not effective in our experience. GH therapy provides a satisfactory auxological result, especially with high doses of GH alone, given for a long period of time. Optimization of the treatment would seem to require the identification of the ideal age for starting therapy, and this is only possible with a specially designed multicenter study.

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.

We evaluated the distribution of TSH levels on dried blood spots (Delfia system-threshold value for recall 20 microU/ml) in 27,282 consecutive samples examined during 1993, in the Emilia-Romagna region. We also evaluated, by questionnaire, the frequency of iodine disinfection in the perinatal period in all centers that do blood spots. We also evaluated the distribution of TSH spot values according to the localization of the center in endemic or not endemic area of the region. Among the parameters we considered, only the sampling day (p0.02) and the maternity center (p0.0001) showed a significant influence on TSH spot values. With regard to the questionnaire, the centers which habitually used iodine disinfection in obstetrics (20/28) showed significantly higher percentages of TSH values over 10 microU/ml than the centers which did not use (3/28) or rarely used (4/28) this type of disinfection (p0.0001). The only center which used regular iodine disinfection of umbilical cord in all newborns, showed a percentage of TSH values over 10 microU/ml (25.8%) and a recall rate (2.5%) significantly higher than all other centers (p0.0001).

We evaluated goiter prevalence and urinary iodine excretion (UIE) in schoolchildren living in three villages of the Appennines in the Bologna district-Castel d'Aiano (CA), Gaggio Montano (GM) and Pietracolora (PC). 175 age-matched schoolchildren living in the urban area of Bologna were considered as control group. In the control area the presence of goiter was documented in 11 out of 175 subjects (6.3%). In the mountain area the presence of goiter was documented in 42 out of 233 subjects (18%) (p0.0001 vs control area). In the urban control area the UIE was 159 micrograms/l (median; range 19-298). In the mountain area the UIE was 119 micrograms/l (median; range 10-286) (p0.001 vs control area). We observed the highest prevalence of goiter and UIE levels100 micrograms/l only in the village of PC, which is still characterized by geographical isolation and rural economy.

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,—Recent studies have demonstrated that coeliac disease can develop months or years after the clinical onset of insulin dependent diabetes mellitus (IDDM).1 Over the last 10 years, 200 consecutive children with IDDM at the onset have been tested for IgG and IgA antigliadin antibodies (AGA) by indirect immunofluorescence2 and for IgA antiendomysial antibodies (EmA) using monkey oesophagus and, more recently, human umbilical cord as substrate.3 An antibody follow up was also performed in 151 of these patients every 3–6 months. At initial testing six diabetic children (four girls and two boys, median age 9 years, range 2–13) were positive for both IgA EmA and IgA AGA (associated with IgG …

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.

Somatotrope cells account for almost 50% of the volume of the pituitary gland, which is usually hypoplastic in subjects with growth hormone (GH) deficiency. Magnetic resonance imaging (MRI) was used to describe the sellar area of two siblings affected by GH gene deletion and hence absent GH secretion. Pituitary size and shape were normal in both subjects and there were no other abnormal findings in the sellar area. In particular, pituitary height (5.6 and 5.1 mm) and volume (268 and 229 mm3) in the two patients were within the normal range for age and higher than the usually reported values in GH deficient subjects. Our results suggest that the amount of GH secreted from the pituitary may have little influence on the dimensions of the gland.

Comparative study of the incidence of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (21ase-def CAH) and clinical findings of affected infants diagnosed via newborn screening versus case survey only in the Emilia-Romagna region of Italy.Neonatal mass screening (from March 1980 to September 1983-Period A, and from March 1991 to August 1995-Period C) and case survey study (from 1980 to June 1995; case survey alone from October 1983 to February 1991--Period B) were performed by the Regional Referral Center for Neonatal Screening for Endocrine-Metabolic Disease with a laboratory (Central Laboratory, S. Orsola Hospital, Bologna) and clinical (First Pediatric Clinic, University of Bologna, S. Orsola Hospital, Bologna) component. A population-based sample of 420 960 newborns consecutively born in the Emilia-Romagna region from March 1980 to August 1995 were studied. Spot 17-OH-progesterone (nmol/L blood) was tested by the radioimmunoassay method after sample extraction during Period A and by fluoroimmunometric time resolved method without sample extraction during Period C. Serum 17-OH-progesterone (ng/dL or nmol/L) was tested by the radioimmunoassay method (Diagnostic Product Corporation Kit, Los Angeles, CA). The case survey was performed by means of a questionnaire sent to all regional centers dealing with pediatrics, neonatology, endocrinology, and pediatric surgery.Thirteen classic 21ase-def CAH were diagnosed by means of neonatal screening (combined A and C periods). One true and one questionable false-negative cases were identified. The incidence of classical 21-hydroxylase deficiency for the white population was 1:15 518 (95% confidence limits 1:9249-1:28 400) by neonatal screening plus case survey, 1:18 105 (95% confidence limits 1:10 365-1:35 041) by neonatal screening alone and 1:25 462 (95% confidence limits 1:12 925-1:59 043) by case survey alone. The sensitivity and specificity of screening for classic CAH were 83% and 99.8% for Period A and 90% and 99.2% for Period C, respectively. The percentage of salt-wasting forms and the male/female ratio were higher during the neonatal screening period than during the case survey only. Sixty-one percent of classic CAH patients benefited from a prompt diagnosis. Nonclassical 21ase-def CAH cases detected via screening and case survey were also reported.Even in a region with adequate neonatal services, clinical diagnosis alone of classic CAH might be delayed or misinterpreted and salt-wasting crises could cause neonatal deaths. CAH screening is thus an effective tool for diagnosing affected male infants without a family history of CAH and for preventing salt loss. However, to achieve maximal benefit from screening, quick procedures are necessary for notification of positive results and beginning prompt treatment. The possibility of false-negative cases indicates that clinical observation should never be abandoned, even with ongoing screening programs.