Lodovico Benso

Turner's syndrome in Italy: familial characteristics, neonatal data, standards for birth weight and for height and weight from infancy to adulthood.

In 1990, the Italian Study Group for Turners Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross‐sectional data and longitudinal growth profiles of 772 girls with Turners 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.

Differences in size at birth are determined by differences in growth velocity during early prenatal life.

Physiologic interindividual differences in neonatal size are traditionally thought of as determined by differences in fetal growth occurring only in the second half of pregnancy. Whether possible differences in early intrauterine growth velocity are the effect of random growth fluctuations or may affect size at birth is still debated. This article aims at evaluating to what extent differences in neonatal size are accounted for by differences in fetal growth velocity. We analyzed the fetal growth of 130 healthy singletons for whom head (HC) and abdomen (AC) circumferences and femur diaphysis length (FDL) longitudinal profiles were available, together with the measures of weight (BW), length (BL), and head circumference (BHC) at birth. Individual profiles were fitted with ad-hoc models. Neonatal traits were transformed into standard deviation scores (SDS). Neonates in the upper third of BW-SDS distribution (3618 ± 43 g, mean ± SEM) had, at 22 wk of gestational age, AC growth velocity higher by 0.55 ± 0.10 mm/wk than those in the lower third (2902 ± 36 g). Neonates in the upper third of BL-SDS distribution (51.7 ± 0.21 cm) had, at 20 wk, FDL growth velocity higher by 0.11 ± 0.05 mm/wk than those in the lower third (48.2 ± 0.18 cm). Neonates in the upper third of BHC-SDS distribution (35.7 ± 0.13 cm) had, at 18 wk, HC growth velocity higher by 0.57 ± 0.20 mm/wk than those in the lower third (33.3 ± 0.11 cm). The differences in growth velocity remain constant throughout the second and third trimester for AC, and tend to vanish in the third trimester for HC and FDL. The differences in fetal growth velocity, which in our study were observed as early as mo 4, suggest that the genetic component plays an important role in fetal growth and is precociously expressed.

Final Height in Sexually Precocious Girls after Therapy with an Intranasal Analogue of Gonadotrophin-Releasing Hormone (Buserelin)

Twenty-two girls affected by sexual precocity with impaired final height prognosis were followed until they achieved final height. Twelve of them were treated with an intranasal (D-Ser6)-gonadotrophin-releasing hormone (GnRH) analogue (buserelin) administered at a mean dose of 25 micrograms/kg/day (range 20-32) for a mean period of 14 months (range 8-18). Ten girls refused treatment. Mean final height of the treated girls was 157.3 +/- 8.2 cm, significantly (p = 0.03) higher than the 149.7 +/- 5.5 cm of untreated patients. Treated girls surpassed midparental height (+1.7 cm) while untreated girls reached the lower part of target zone (-3.5 cm). Our data suggest that intranasal buserelin treatment preserves final height in girls with sexual precocity and initially impaired height prognosis.

Longitudinal distance standards of fetal growth

Background. Most ultrasonographic fetal growth norms are derived from cross‐sectional data or from longitudinal data treated as coming from cross‐sectional studies, although only longitudinal models may detect particular aspects of fetal growth shape, such as peak of growth velocity.

Magnetic resonance and the diagnosis of short stature of hypothalamic‐hypophyseal origin

Magnetic resonance imaging was performed in 23 patients with short stature (7 had multiple pituitary hormone defect, 11 had isolated growth hormone deficiency and 5 had normal variant short stature) to investigate if there is a relation between magnetic resonance findings and results of endocrine tests. Magnetic resonance imaging of patients with multiple pituitary hormone deficiency or with serious isolated growth hormone deficiency (growth hormone < 3 μg/l) revealed an interrupted pituitary stalk and ectopic neurohypophysis or a mass. In patients with less serious isolated growth hormone deficiency (growth hormone > 3 μg/l) or with normal variant short stature, the technique revealed a normal or hypoplastic hypophysis. Magnetic resonance appears to be a useful second‐level diagnostic tool in defining the type of alteration in growth defects of endocrine origin.

Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: An interim long-term analysis

SummaryThe low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) age 3–12 yrs, after a median period of 14 mo.s is reported. Children with connective tissues (CTD) and glomerular disorders (KD) were randomly allocated to DFZ or PDN. Anthropometric measurements and maturity ratings were performed. Mean daily doses of PDN (or DFZ equivalent), from 0.57 to 0.64 mg/kg (DFZ 0.92 to 0.94 mg/kg) to induce control and from 0.19 to 0.93 mg/kg (DFZ 0.34 to 0.36 mg/kg) to maintain disease under control were given in CTD and KD, respectively. The increase in bone age delay over time was significantly>for PDN(-4.0 mo/yr) than DFZ (-1.8 mo/yr) in the overall group. The increases in statural age delay and loss over time were significantly> for PDN (-5.9 and-5.9 mo/yr) than DFZ (-2.4 and-2.4 mo/yr), only in children with “taller” midparents. Although doses of DFZ 1.1–1.8 times those of PDN were given, growth retardation in PDN-treated children was nevertheless 2.3–2.5 times that in DFZ-ones.

Variation of bone age progression in healthy children

Bone age assessments were related to auxological variables in 407 Italian boys, between 7 and 12 years of age, in order to elucidate the factors that affect the rate of skeletal maturation and to examine the possibility of using measures of skeletal maturation to evaluate individual patients. Using the radius—ulna—short bones (RUS) method of assessment, bone age velocity was greater in the Italian boys than for the UK reference standards, although there was considerable interindividual dispersion around the mean. Bone age velocity and height velocity were poorly correlated, and there was little correlation between skeletal and pubertal maturation. There was a slight positive correlation between bone age velocity and height SDS and between bone age velocity and body mass index. Bone age estimations using RUS were greater than those obtained using the carpus. In conclusion, the marked interindividual deviation in measured bone ages makes it difficult to relate data on an individual basis to other measures of growth and maturation. □ Bone age, bone age velocity, skeletal maturation, height, height velocity, body mass index

The use of local reference growth charts for clinical use or a universal standard: A balanced appraisal

224 A much-debated topic is whether a growth chart should be local, national or international. On the one hand, if we consider that, by definition, a reference chart describes the anthropometry of a given population, we can conclude that we need as many reference charts as the number of different populations, no matter whether their anthropometric differences are ascribable to ethnic characteristics or to environmental, nutritional, socioeconomic, and health conditions. On the other hand, if we believe that all healthy children under unrestricted conditions fully express their growth potential, and that growth potential varies between individuals but not between populations, then a unique standard should apply to all children.

Is the persistence of isolated GH deficiency in adulthood predicted by anatomical hypothalamic-pituitary alterations?

The aim of this study was to verify the persistence in adulthood of GH deficiency diagnosed in childhood and treated with hGH in childhood and to study whether anatomical hypothalamic-pituitary alterations evaluated by magnetic resonance (MR) imaging could predict it. To this goal, in six GHD adults (3 males and 3 females aged 17.2–24.5 yr, BMI 21.8±1.3), we studied anterior pituitary hormone response to GHRH (1 μg/kg iv)+pyridostigmine (120 mg po) + GnRH (100 μg iv) + TRH (400 μg iv) + hCRH (100 μg iv) as well as brain MR imaging. In childhood, the diagnosis of severe isolated GHD had been done based on auxological findings as well as on GH response <7 μg/L after two classical provocative stimuli. In the present study, hormonal responses showed the persistence of severe isolated GHD in 4 out of 6 patients (peak, mean±SEM: 3.8±0.6, range 2.6–4.8 μg/L). In these patients, IGF-I levels were found low or low-normal. In other 2 patients, a clear GH response to stimulation (peak: 51.3 and 43.0 μg/L, respectively) together with normal IGF-I levels were found. No other anterior pituitary hormone deficiency was present in all subjects. MR imaging showed pituitary hypoplasia in all patients with persistent GHD; in 2 out of them, pituitary stalk interruption and ectopic neurohypophysis was also present. On the other hand, MR imaging showed normal hy-pothalamo-pituitary morphology in the 2 subjects with normal somatotrope response. In conclusion, our present data indicate that testing with a potent stimulus such as GHRH+pyridostigmine is a reliable method to assess the persistence of GH deficiency which associates with anatomical hypothalamic-pituitary alterations at the MR imaging. Patients with transient GH deficiency in childhood and normal pituitary GH reserve in adulthood have normal hypothalamic-pituitary MR imaging.