Growth hormone neurosecretory dysfunction in a boy with hypohidrotic/anhidrotic ectodermal dysplasia: definition of short stature, molecular characterization and long-term hGH replacement treatment to final height.

Anhidrotic/hypohidrotic ectodermal dysplasia is a rare disorder, genetically heterogeneous, commonly X-linked recessive inherited, characterized by hypoplasia up to the absence of the eccrine glands with hypo-anhidrosis and secondary hyperpyrexia, hypodontia and some typical craniofacial features. Some papers have described how these patients may show poor growth, while other recent research shows normal growth. We report a boy with anhidrotic/hypohidrotic ectodermal dysplasia and growth hormone neurosecretory dysfunction, an association not previously reported, and we discuss the possible causes as well as the patient's response to growth hormone treatment until he reached final height.

Congenital hypothyroidism in Young-Simpson syndrome.

We describe a patient with the clinical spectrum of Young-Simpson syndrome. This rare genetic disorder is characterized by congenital hypothyroidism, mental retardation and blepharophimosis. Young-Simpson syndrome is, at present, poorly known to endocrinologists and pediatricians, and should be included in the differential diagnosis of congenital hypothyroidism. It is important to underline that the association of congenital hypothyroidism, blepharophimosis and ptosis allows an exact clinical diagnosis, since the majority of other clinical aspects are common to other disorders.

Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status?

BACKGROUND: Weight loss is common in juvenile idiopathic arthritis (JIA) and has been positively correlated with an increase in the production of proinflammatory cytokines. OBJECTIVE: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA. METHODS: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls. RESULTS: Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m(2); p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively). CONCLUSIONS: Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA.

Precocious, early and fast puberty in males with Chiari I malformation.

Type I Chiari malformation is a disorder characterized by a displacement of the cerebellar tonsils through the foramen magnum into the upper cervical spinal canal and, contrary to type II Arnold-Chiari malformation, without the presence of myelomeningocele. As described in the literature, patients suffering from Arnold-Chiari malformation with myelomeningocele can frequently present with precocious puberty, whereas only one report shows an association between Chiari I malformation and early puberty. We describe three young males--8.8, 9.4 and 10.4 years old--who were diagnosed with precocious, early and fast puberty associated with type I Chiari malformation. In patients 2 and 3, the reason for diagnostic management recommendation was a rapid progression of pubertal development over one year. None of the patients manifested hypophyseal-hypothalamic axis dysfunction other than sexual precocity. Neurological and ophthalmological examinations were normal in all patients. Our data show that type I Chiari malformation can be considered one of the possible causes for precocious, early and accelerated puberty in male patients, suggesting the need to carry out brain nuclear magnetic resonance imaging in order to investigate the presence of this malformation.

Marginal and internal adaptation of stratified compomer-composite Class II restorations.

Different approaches have been proposed to improve the adaptation of Class II restorations, including applying low-elasticity modulus base liners. This in vitro fatigue test (or study) evaluated the influence of the compomer base-lining configuration on restoration adaptation. Direct Class II MOD box-shaped composite restorations with or without base and lining (n=3x8) were placed on intact human third molars with proximal margins 1 mm above or under the CEJ. The compomer (Dyract) was applied as a 1 mm-thick lining or as a base, closing proximo-gingival margins. Marginal adaptation was assessed before and after each phase of mechanical loading (250,000 cycles at 50N, 250,000 cycles at 75N and 500,000 cycles at 100N); internal adaptation was evaluated after test completion. Gold-sputtered resin replicas were observed in the SEM and restoration quality evaluated in percentages of continuity (C) at the margins and within the internal interface after sample section. Mechanical loading did not influence adaptation to enamel, while it adversely affected restoration adaptation to dentin for the full composite and compomer-base restorations (C varied, respectively, from 95.2 to 75.3% and from 98.0 to 10.6%). The internal adaptation quality showed the same general trend, however, with reduced scores of continuity. In this experimental condition, application of a low elasticity modulus layer under the restorative material proved advantageous but the compomer should not contact the gingival margins.

Etiology and age incidence of precocious puberty in girls: a multicentric study.

We review the etiology and age incidence of precocious puberty in 438 girls examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were 6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30 (9.9%) were due to previously diagnosed intracranial abnormalities and the remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of neurogenic CPP tended to be higher in girls under 4 years of age while the frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9 years, but no statistically significant differences were found. Interestingly, some CNS anomalies either of tumoral or congenital origin were detected at presentation in 7% of the girls aged over 7 years. Other related or coincidental clinical anomalies, mainly due to genetic diseases, were observed in 22/304 (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%) girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this study. Neurogenic anomalies or other coincidental or related clinical findings were observed in the remaining 26%. The increased frequency of idiopathic CPP in girls aged over 7 years may suggest an early, but otherwise normal onset of puberty in many of these girls as a consequence of the trend towards earlier maturation. Nonetheless, the finding of CNS anomalies also in the older patients, raises the question of whether these patients should undergo a complete diagnostic work-up.

Comparison of quantitative calcaneal ultrasound and dual energy X-ray absorptiometry in the evaluation of osteoporotic risk in children with chronic rheumatic diseases.

Osteoporosis is a common complication in children with chronic rheumatic diseases (CRD). Although dual energy X-ray absorptiometry (DXA) is increasingly being used to determine bone mineral density (BMD) in children, it exposes the subject to ionizing radiation and does not provide a measure of true bone density; in fact, in growing bones the increase in BMD is mainly caused by the increase in bone size. In recent years, quantitative ultrasound techniques (QUS) have been used in radiation-free assessment of bone density and "bone quality" by measurement of the ultrasound waves attenuation by bone (BUA). In the present study we made a direct comparison of BUA in the calcaneum, determined by the pediatric contact ultrasound bone analyzer (CUBA) with lumbar BMD measured by DXA, in a group of 6-18-year-old patients with CRD. The study group consisted of 53 patients affected with juvenile rheumatoid arthritis (n = 29), systemic lupus erythematosus (n = 13), and juvenile dermatomyositis (n = 11). Mean age was 13.02 +/- 2.69 years. In 22 patients (19 girls, 3 boys) both DXA and CUBA were repeated after 1 year in order to assess the mean percentage rate of BMD and BUA change over this time. Both lumbar spine BMD and calcaneal BUA measurements were lower in the CRD patients compared with a control group (P < 0.001). Calcaneal BUA was significantly correlated (r = 0.83, P < 0.001) with lumbar spine BMD. Age and sex correction (Z-score) did not change the relationship between BUA and BMD (r = 0.80, P < 0.001). A significant correlation between the mean percentage of variation (delta%) of BMD and BUA (r = 0.76, P < 0.001) was also demonstrated in the 22 patients who were evaluated prospectively. Portability, ease of use, lower cost, and absence of radiation make CUBA a promising means of evaluating BMD in children.

Nocturnal melatonin patterns in children.

Time patterns in nocturnal concentrations of circulating melatonin of children are quantified in 8 girls and 8 boys, 8.7-16.8 yr of age, classified by Tanner pubertal stage. Between 1900 and 0700 h, each provided blood samples at 30-min intervals for melatonin RIA. Associations with gender, body mass index, and chronological and pubertal age determined by multiple linear regression and ANOVA reveal that the area under the curve of 12-h melatonin concentrations was affected by pubertal rather than chronological age, an effect to which data collected during darkness contributed the most. Each data series was also analyzed by a least squares spectrum at frequencies of 1-20 cycles/day. Ultradian changes with periods of 3.4 and 1.5 h, putatively associated with rapid eye movement sleep cycles, characterize nocturnal melatonin in boys and girls.

Interleukin-6 release by cultured peripheral blood mononuclear cells inversely correlates with height velocity, bone age, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 serum levels in children with perinatal HIV-1 infection.

Spontaneous and phytohemagglutinin (PHA)-stimulated interleukin (IL)-6 release by cultured peripheral blood mononuclear cells was related to height velocity, bone age, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) serum level standard deviation scores (SDS) of 32 children [aged 91 (median; range 13-151) months] with human immunodeficiency virus-type 1 (HIV-1) perinatal infection and severe disease. Spontaneous and PHA-stimulated IL-6 release inversely correlated with height velocity, bone age, IGF-I, and IGFBP-3 SDS. Ten children with height velocity SDS -2, showed higher spontaneous and PHA-stimulated IL-6 release and lower IGF-I and IGFBP-3 SDS (irrespective of CD4-positive T-lymphocyte counts, viral load, liver disease, or nutrition status). IL-6 overproduction may be a mechanism of IGF-I and IGFBP-3 down-regulation and impaired linear growth in children with perinatal HIV-1 infection. Growth-promoting strategies, including targeted anticytokine treatments, could be devised for such children.

[Precocious puberty, Gh deficiency and obesity can affect final height in patients with myelomeningocele: comparison of males and females]. / Pubertà precoce, deficit di GH ed obesità possono alterare la statura finale di pazienti con mielomeningocele: confronto fra maschi e femmine.

Patients with myelomeningocele show an increased incidence of endocrinological disorders during their childhood. These disorders can ulteriorly affect the adult height of these patients who are already extremely short. In the present study we determined the final height in 21 patients (11 females aged 20.55 +/- 3.54 years; 10 males aged 20.99 +/- 2.94 years) with myelomeningocele. The endocrinological implications were investigated by clinical and laboratory assessment at control and an accurate retrospective evaluation of individual clinical history. Auxological data indicated that in male patients mean final height was significantly less (P < 0.05) than target height, but in females the difference between final height and target height was even more marked (P < 0.001). Comparison of SDS for adult height between males (-2.04 +/- 1.89) and females (-4.36 +/- 2.24) evidenced a statistically significant difference (P < 0.05). The analysis of endocrinological data showed that 7 females had had precocious puberty not treated; no case of precocious puberty was evidenced in males. In 4 females we observed plasmatic IGF-1 and IGFBP-3 concentrations significantly reduced either for chronological age and pubertal stage; this finding emerged in only 1 male. Plasmatic thyroid hormone and adrenal steroid concentrations resulted normal in both groups. Finally, obesity, considered as BMI > 90%, resulted present since childhood in 4 females and 2 males. Our data show that females with myelomeningocele have a statistically greater decrease of their adult stature respect to males. This difference is probably due to a more significant incidence in females of endocrinological diseases. Thus, we believe that a better statural prognosis may be joined in these patients (particularly in girls), through a careful endocrinological follow-up, performed from their births, in order to ensure a prompt identification and treatment of the cases of precocious puberty, impaired GH secretion or obesity.

Adult height comparison between boys and girls with precocious puberty after long-term gonadotrophin-releasing hormone analogue therapy.

We examined 22 girls and 11 boys with idiopathic precocious puberty (IPP) treated with a GnRH analogue for a period of about 4 y. The purpose of our study was to evaluate possible differences between the two sexes in bone growth and skeletal maturation during treatment and in the achievement of final height, and also to study the relative contribution of particular hormones--sex steroids, DHEAS, GH and IGF-I--during the pubertal growth spurt. At the beginning of therapy mean chronological age (CA) was 7.61 +/- 0.84 y in boys and 7.32 +/- 1.06 y in girls. After the first year of treatment, growth velocity and delta bone age/delta chronological age (deltaBA/deltaCA) ratio had declined significantly in both groups. At the end of therapy we observed a statistically relevant increase in predicted adult height in both sexes, with a more appreciable mean gain (expressed as SDS) being achieved by male patients. During the first year following discontinuation of treatment, a significant increase in the deltaBA/deltaCA ratio was observed in both males and females; by contrast, growth velocity increased only in male patients. Adult height SDS was thus greater in boys (0.13 +/- 0.91) than in girls (-0.62 +/- 0.88, p < 0.05). With regard to endocrinological data, oestradiol and testosterone were significantly reduced during the first year of therapy, while DHEAS levels increased slightly in both sexes throughout the course of treatment. GH peak after clonidine and IGF-I concentrations remained unchanged in both groups. Also, a study of nocturnal GH secretion (10 subjects) showed no noteworthy decrease in any of the patients, whether in terms of mean GH, of the sum of pulse amplitudes, or of pulse frequency. In conclusion, our data indicate that boys achieve more significant results in terms of adult height than girls. With reference to endocrinological data, the effect of sex steroids on bone maturation seems to be more significant than previously thought, and we hypothesize a different role for androgens and oestrogens in regulating height velocity and bone maturation in both male and female subjects during pubertal growth spurt.

[Dynamic posturography in normal subjects]. / La posturographie dynamique dans les sujets normaux.

The relative lack of data on the dynamic posturography led us to start a study in order to give our contributions to the standardization of M1, M2, M3, response parameters in normal subjects. Our research was carried out on 35 normal subjects aged 21 to 50. All of them were standing in Romberg's position on a Tönnies model board in a normally lit and ventilated room. We performed two tests: the first one open-eyed staring at no point, the second, 5 minutes later, closed-eyed. The EMG signals were obtained by surface electrodes on triceps sural and front tibial muscles. The EMG recording was determined by a "tilt" movement of the board at a steady speed of 50 per sec. and 4 wide. We use a XT 286 IBM computer with "T POST" software for checking and testing the data. Our results showed a significant variation in the value of the duration parameter in open-eyed and closed-eyed tests. Latency and area values were inferior to those obtained by other authors, except for Diener and Dichgans (3) whose results differ in latency value only.