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.

Thyroid hypoplasia as a cause of congenital hypothyroidism in Williams syndrome.

In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. However, the frequency of biochemical thyroid assessment, particularly in the first year of life, is being debated. In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. Therefore, treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.

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.

Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

Reversible weight gain and prolactin levels--long-term follow-up in childhood.

In adult patients weight gain is a frequent complaint of hyperprolactinaemia and it has been associated with a high prevalence of obesity. Normalization of prolactin (PRL) levels result in weight loss. The nature of this link is poorly defined. In this report we describe a 14 year-old female with primary amenorrhea and persistent progressive weight gain. The patient's height, weight and BMI were 152 cm, 70 kg, and 30.3 kg/m2, respectively. Basal hormonal investigation showed normal free thyroxin, TSH, IGF-I, cortisol and ACTH values. Serum PRL level was very high (16,278 mIU/l; normal range 63-426 mIU/l). Magnetic resonance imaging scan showed the presence of a pituitary microadenoma. Treatment with the non-selective dopamine agonist pergolide caused a significant reduction of serum PRL concentration with a remarkable decrease of body weight. During follow-up, repeat MRI scan revealed disappearance of the microadenoma. The reduction of the daily dose of pergolide was associated with an increase of serum PRL with significant weight gain. A further reduction of body weight was subsequently observed with an increase of pergolide dosage. Serum PRL measurement may be useful as part of the endocrine work-up of obese children with a history of unexplained recent weight gain, especially if associated with pituitary-gonadal axis dysfunction. The relationship between PRL secretion and weight change needs to be examined in prospective larger studies.

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.

Initial experience with laparoscopic adrenal surgery in children: is endoscopic surgery recommended and safe for the treatment of adrenocortical neoplasms?

Through a review of 83 cases reported in literature, including our experience of two successful right laparoscopic adrenalectomies performed in a 3-year-old girl for androgen-secreting adenoma and in a 9-year-old male for pheochromocitoma, we have anaIyzed the indications, the techniques and the results of laparoscopic or retroperitoneoscopic adrenalectomy in children. Nineteen pheochromocytomas, 18 neuroblastomas, 15 adenomas, 12 ganglioneuromas, 9 hyperplasias, 2 carcinomas, 1 teratoma and 1 adrenogenital syndrome have been treated with excellent results (follow-up 1 month to 4 years) with no evidence of recurrence. The age range is from 1 month to 16 years with an equal female/male ratio. The tumor size range from 10 mm to 80 mm with approximately a mean of 40 mm. Sixty-three laparoscopies of which 54 lateral and 9 anterior have been performed versus 14 posterior retroperitoneoscopies. Regarding right adrenalectomy, 29 were laparoscopic and only 2 retroperitoneoscopic. With regards to left adrenalectomy, 23 were laparoscopic and 9 retroperitoneoscopic. Looking at bilateral lesions, these tumors were approached laparoscopically in 6 cases alternating both sides and 1 retroperitoneoscopically (this case was already operated on the other side). The operative time ranged from 25 minutes in newborn to 320 minutes in bilateral cases with an average of 120 minutes. Conversion rate is higher in retroperitoneoscopy (30%) (4 cases out of 13), than laparoscopy (6%) (4 cases out of 63). Specifically, for right retroperitoneoscopic adrenalectomy conversion rate was 100% (2 cases out 2), for left retroperitoneoscopic adrenalectomy 22.2% (2 cases out 9), for right laparoscopic adrenalectomy 6.8% (2 cases out of 29) and for left laparoscopic adrenalectomy 8.6% (2 cases out of 23). Only in 1 case were blood transfusions requested. Hospital stays ranged from 35 hours to 17 days with an average of 4 days. In conclusion the indications of endoscopic adrenalectomy in children are not different from those of traditional surgery and the well-known advantages of laparoscopic adrenal surgery should be applied to pediatric patients. It seems that there is no age and tumor size limits for a well-trained surgical team. Lateral transperitoneal approach is the most utilized with the child positioned in 90-degree flank decubitus. Laparoscopy is undoubtly preferred for right adrenalectomy (93% of cases), while for left adrenalectomy retroperitoneoscopy has been used in 39% of the cases. Considering the conversion rate and on the basis of our experience with adults, we recommend laparoscopic adrenalectomy for both right and left adrenal lesions, but we think that the pediatric surgeon should feel free to choose the approach in which he/she is more skilled. However, the best surgical result will be achieved if the pediatric and adult surgeon collaborate with their different experiences. Lastly, we suggest the use of new technological devices such as Ultracision Harmonic Scalpel which was a critical factor in our two successful right adrenalectomies.

[Stress urinary incontinence in women. Physiopathology and surgical treatment using Burch's technique and TVT]. / Incontinence urinaire d'effort chez la femme. Physiopathologie et traitement chirurgical par les techniques de Burch et TVT.

FROM PHYSIOPATHOLOGY TO TREATMENT: Urinary incontinence on effort in women is due to a default in sub-urethral anatomical structure, which leads to incontinence on effort (coughing, laughing, carrying heavy weights, physical activity). When re-education fails, surgical treatment using Burch's technique or the placing of sub-urethral TVT (Tension free Vaginal Tape) is generally proposed. BURCH'S TECHNIQUE: Burch's technique consists in an upper tract colposuspension via coelioscopy or laparotomy, under rachis or general anaesthesia. In the literature, the following rates of complete cure have been presented: 64 to 87%, 75 to 95% and 63 to 89% respectively in the short, median and long term together with the cure of certain complications (vesicular instability, dysuria, secondary prolapse, infections). THE TVT TECHNIQUE: Developed in the early nineties, the placing of TVT is a mini-invasive technique requiring the use of polypropylene tape inserted vaginally under the urethra under rachis or local anaesthesia. It is associated with over 80% median term clinical efficacy and rare complications (vesicular perforation, arterial wounds, perineal haematoma, dysuria, infections).

[Economic comparison of 2 surgical techniques fr the treatment of stress urinary incontinence in women: Burch's technique versus the TVT technique]. / Comparaison économique de deux techniques chirurgicales de traitement de l'incontinence urinaire d'effort chez la femme: technique de Burch contre technique TVT.

The TVT device (Tension-free Vaginal Tape) is used in our Hospital to treat stress urinary incontinence, resulting in an excess cost for the Pharmacy. The Burch technique, used previously, does not require any specific medical device, but is invasive and requires a longer hospital stay. The objective of this study was to compare the financial impact of these two techniques, by defining the discriminant costs. Seventeen isolated Burch procedures and twenty one TVT procedures were included. The costs analysed concerned medical devices, medicinal products, laboratory procedures, operating time, hospital stay and duration of postoperative follow-up. The Burch procedure cost FFR 26,322 and the TVT procedure cost FFR 10,958. The TVT technique reduces the cost of hospitalisation and represents an economy of operative equipment and nursing workload (reduction of operating time and postoperative stay).

Anesthetic and surgical factors affecting open heart surgery patients leading to cerebrovascular accident--retrospective study at King Khalid University Hospital.

Stroke after coronary bypass grafting (CABG) is often disabling. The incidence of ischemic stroke may approach 3% to 5%. Several risk factors have been identified including previous history of stroke, prolonged cardiopulmonary bypass time, and postoperative atrial fibrillation. Retrospective study during the period 1992-1995 was undertaken to determine the incidence, risk factors of neurological deficit after open-heart surgery at King Khalid University Hospital, Riyadh, Saudi Arabia. There were 350 patients who were subjected to CABG, 10 patients (2.8%) were found to suffer from cerebrovascular accidents (CVA) following open-heart surgery. In 18 patients, the complaint lasted more than 24 hours (stroke), while 2 patients developed transient ischemic attacks (TIA). Five factors were found to be associated with increased risk of post cardiac surgery CVA. These factors are postoperative atrial fibrillation, carotid bruit, past history of heart failure, past history of CVA and smoking. The authors concluded that it is necessary to start a prospective study to verify the area of improvement with regards to technique, selection of patients and mode of perfusion during cardiopulmonary bypass (CPB).

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.

The anesthetic and intensive care management of pulmonary hemosiderosis in a child--case report.

Pulmonary hemosiderosis represents challenges during anesthesia and intensive care management. This is a report of a case of idiopathic pulmonary hemosiderosis in a child which was successfully managed during anesthesia and in the intensive care unit with total remission of the disease. The management of this and similar cases are discussed.

[A new growth curve]. / Una nuova curva di crescita.

A growth curve is presented, that using the Tanner and Whitehouse's 50th centile, plots the height versus weight, both for males and females. The age is gives as parameter on the curves. In this way, weight, height and age are merged on a single chart for every sex. After exemplifying its advantages, the simpler relief of deviation from the values of the height-weight medians on the various ages, because the values of weight refer to the real height (and back), not to the age. With the same rule, curves relating to 10th and 90th centiles are processed by Tanner and Whitehouse's values. Collating between them, curves allow some morphological relief. Moreover, for both referred to the 50th centile of Tanner and Whitehouse curves (for the male sex and the female one), is presented a simple mathematical expression of interpolation, which shows and excellent representation of the measured dates. This expression is composed of a third-degree polynomial (cubic), which is fitted to the dates by the method of least square. The result of the correlation height-weight allows both to synthesize the dates in a sole expression and a simpler relief of discordance in the growth.

[The assessment of skeletal age in hypothyroidism during the first year of life. The features of a new method]. / La valutazione dell'età scheletrica nell'ipotiroidismo durante il primo anno di vita. Rilievi con un nuovo metodo.

Determining skeletal maturity in the first year of age with usual methods is often quite difficult. Some years ago, we investigated a new method based on the time of appearance of appreciable ossification centres in the upper limbs with the following succession: humerus head, capitate, coracoid process, hamate, humerus capitulum, greater tuberosity and radius distal epiphysis; in the first month of age it must be associated to knee and foot study. We studied with our method the skeletal maturity of 16 hypothyroid patients before and after 6 and 12 months of therapy; in the first month of age we associated the study of left knee and foot and study of left hand and wrist using Greulich and Pyle's method at 12 months of age. We compared data of hypothyroid patients to data of 399 infants hospitalized in Pediatric Clinic of Florence for infectious diseases or for neonatal hyperbilirubinemia. Our study has showed that skeletal maturity, retarded before therapy, rejoined normal values over a period of time of 12 months of substitutive treatment; it was accelerated in some patients.

[Cockett's syndrome and retro-iliac ureter. A previously unknown and original association apropos of a case and review of the literature]. / Syndrome de Cockett et uretère rétro-iliaque. Une association méconnue et originale à propos d'un cas et revue de la littérature.

The authors report a case of Cockett's syndrome discovered by ilio--cava angiography at a patient who was operated on a bilateral retro-iliac ureter which occasioned an important renal insufficiency. After a review of the literature, it appears it is the first case published with such a pathologic association mentioned.

Spondylo-epiphyso-metaphyseal dysplasia: an atypical variant.

In a 12 years, 10 months-old-girl with severe nanism we observed bone changes of unusual spondylo-epi-metaphyseal dysplasia (S.E.M.D.). The metaphyseal and epiphyseal changes in the long bones were symmetrical and mostly rhizomelic - with the involvement of the iliac bones, tarsal bones with irregular lesions and disproportionally long fibulae; these changes confirm the heterogeneity of the disease.