Patients with complete resection of cranial base chordomas have a prolonged 5-year PFS and OS. Adjuvant proton-beam, carbon ion, and modern fractionated photon radiation therapy techniques offered a similar rate of PFS and OS at 5 years.

Based on the current management protocol, patients with VSs enjoy similar QOL throughout the follow-up period after undergoing observation, radiation therapy, or surgery.

Skeletal age assessment (SAA) is a clinical procedure which is used in determining the SA of children and adolescents. Bone development is influenced by a number of factors, including nutrition, hormonal secretions, and genetics. There are several factors to be borne in mind when using methods of assessing skeletal maturity. These include: Variability among methods, degree of variability in the estimation of skeletal maturation, sources of low accuracy, and dispersion of the values of skeletal maturation. Currently, the main clinical methods for SAA are the Greulich and Pyle (GP) and Tanner and Whitehouse (TW) methods. The GP method has the advantage of being quick and easy to use. A well-trained radiologist takes few minutes to determine the bone age (BA) from a single hand radiograph. The method of TW, however, seems to be more reliable than the GP method. In recent years, the increasing speed in computer sciences and reduction of their cost has given the opportunity to create and use computerized BA estimation system. Despite the fact that the number of automated systems for BAA have increased, most are still within the experimental phase. The use of automated BA determination system, cleared for clinical use in Europe (BoneXpert), has been validated for various ethnicities and children with endocrine disorders. Ultrasound imaging has some limitations that include operator dependence, lower intra-rater and inter-rater reliability of assessment and difficulties with standardization of documentation and imaging transfer. Magnetic resonance imaging (MRI) is noninvasive alternative tool for SA assessment in children. However, few studies have been reported on this topic, and further research is needed to evaluate the reliability and validity of MRI BAAs. In conclusion, at present radiographic methods for the assessment of BA remain the gold standards. Whatever method one adopts, it is essential to minimize the causes of imprecision by taking care to consider the quality of the X-ray. Moreover, it is imperative to assume a correct hand positioning because poor positioning can change the appearance of some bones. It is also preferable to employ scoring methods to these techniques and percentiles rather than BA in years and months. In addition, the possible differences in maturation among different population should be kept in mind.

Overweight/obesity, thyroid hypoechogenicity, and nonsynonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.

Objective: To evaluate longitudinal growth, pubertal development and ®nal height in patients with congenital hypothyroidism (CH) detected by a neonatal screening programme, and to identify factors potentially affecting growth outcome. Patients: Fifty-®ve patients (41 females) detected by neonatal screening and followed longitudinally from the time of diagnosis and treatment (25^5 days) up to the age of 17^0X5 years were evaluated retrospectively. Results: Pubertal development began and progressed normally in both males and females. In boys, a testicular volume of 4 ml was reached at 11X3^1X0 years. In girls breast enlargement (B2) occurred at a mean age of 10X3^1X2 years and the mean age of menarche was 12X5^1X2 years. The onset and the progression of puberty were independent of the aetiology, the severity of CH and the timing of the beginning of treatment. Girls treated with an initial amount of L-thyroxine (L-T 4 ) greater than 8 mg/kg per day showed an earlier onset of puberty (B2 9X4^0X9 years; menarche 11X5^0X8 years) compared with girls treated with a lower initial dose of L-T 4 (B2 10X5^1X2 years; menarche 12X6^1X2 years; P , 0X02). However, both groups attained a similar ®nal height (20X1^1X0 SDS and 0X4^1X0 SDS, respectively), which in both cases was above the target height P 0X03X All the patients in the study attained a mean ®nal height (0X1^1X1 SDS) within the normal range for the reference population and above the target height 20X9^0X9 SDS, P , 0X0001X No signi®cant relationship was found between ®nal height and severity of CH at diagnosis, initial L-T 4 dosage or aetiology of the defect. Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar mean ®nal height (0X1^1X1 SDS, 0X5^1X0 SDS and 20X5^1X0 SDS, respectively), which was in all cases greater than target height 21X0^0X9Y 20X6^0X8Y 20X9^0X8 respectively; P , 0X05X Conclusions: Our results suggest that conventional management of children with CH detected by neonatal screening leads to normal sexual development and normal adult height, and that the major factor determining height in these children is familial genetic growth potential.

To evaluate the effect of different initial levothyroxine (LT4) replacement doses on growth and intellectual outcome in patients with congenital hypothyroidism (CH) detected by neonatal screening program, the longitudinal growth and intelligence quotient (IQ) were assessed and compared at 4 years of age in 83 patients with CH. The patients were divided into three groups according to the initial LT4 dose used: (1) group 1 (n = 42) received the previously recommended dose of 6.0-8.0 microg/kg per day; (2) group 2 (n = 21) received a dose of 8.1-10.0 microg/kg per day; (3) Group 3 (n = 20) a dose of 10.1-15.0 microg/kg per day. The IQ, evaluated by the Wechsler Preschool and Primary Scale of Intelligence test at 4 years of age, was significantly higher in group 3 (IQ 98 +/- 9) compared to group 1 (IQ 88 +/- 13; p < 0.05) but not compared to group 2 (IQ 94 +/- 13). However, the IQs were below the normal range (< 85) in six patients from group 2 (28%), but in none of the patients from group 3 (p = 0.03). Patients from group 3, with severe CH at diagnosis, had an IQ (97 +/- 9) at 4 years of age, which was not different from that of patients from the same group with moderate CH at diagnosis (IQ 99 +/- 9). Similar results were also observed in patients from group 2 however, mean IQ scores in these patients (93 +/- 12) were several points lower than those observed in patients from group 3 (95 +/- 15). After the first month of treatment, optimal serum levels of thyroxine (T4) and free thyroxine (FT4) were achieved in all groups, however, only patients from group 3 were able to normalize thyrotropin (TSH) (group 1, 16.0 +/- 12.0; group 2, 9.2 +/- 10.0; and group 3, 2.4 +/- 3.3 mU/L; p < 0.0001). Twelve patients from group 2 treated with an initial LT4 dose above 9 microg/kg per day were able to normalize TSH levels within the first 3 months of life and this resulted in a better IQ (97 +/- 16) compared to the remaining patients from the same group (IQ 90 +/- 9). In the whole group of 83 patients the IQ at 4 years of age was positively correlated to both initial LT4 dosage (r = 0.27, p < 0.02) and FT4 concentrations after the first month of treatment (r = 0.29, p < 0.02), and negatively correlated to TSH concentrations after the first month of treatment (r = -0.27, p < 0.02). No significant differences were observed in height, weight, head circumference, and bone age maturation among the three groups of patients. No clinical signs or symptoms of overtreatment were observed during follow-up in patients receiving the higher LT4 dosage. Our results indicate that high LT4 starting doses rapidly normalize serum TSH concentrations resulting in an improvement of the IQ at 4 years of age, even in patients with severe CH at diagnosis. Growth and bone age maturation are not affected by such a high dose.

Background: The intellectual outcome in children with congenital hypothyroidism detected by neonatal screening is generally good; however, subtle neurological dysfunctions, subnormal IQ, or both, have been reported. Objective: To evaluate the intellectual outcome in 12-year-old patients with congenital hypothyroidism, detected by neonatal screening, in an attempt to identify factors that may affect intellectual development. Methods: The intelligence quotient (IQ) of 40 children with congenital hypothyroidism was evaluated at 12 years of age, using the Wechsler Intelligence Scale for Children -Revised, and compared with the IQ of 40 healthy siblings (control group). Results: The mean IQ score (88.4 Ϯ 13.1) was not significantly different from that of the control group (93.4 Ϯ 10.7). Thirteen patients showed subnormal IQ score (72.4 Ϯ 4.9) compared with their siblings (86.7 Ϯ 9.6; P < 0.0001) and with the other patients (96.1 Ϯ 9.6; P < 0.0001). The low IQ score was associated with lower serum concentrations of thyroxine at diagnosis, poor treatment compliance during follow-up and lower familial IQ. Interviews with parents of children with congenital hypothyroidism revealed that a refusal to acknowledge the disease was linked to poor attention to the child's emotional life and to poor treatment compliance in some cases (11%). Conclusion: Even though the mean IQ score in patients with congenital hypothyroidism falls within normal for the control population, low IQ scores may be present in patients with severe hypothyroidism, inadequate compliance to replacement therapy during follow-up and poor parental pedagogic attitude.

We report a large Italian pedigree in which five out of six males are affected by a syndrome, following an X-linked inheritance pattern, characterized by ichthyosis, hypogonadotropic hypogonadism, and anosmia. The concurrence of features of X-linked ichthyosis (XLI) with those of Kallmann syndrome, another disease often inherited as an X-linked trait, prompted us to perform biochemical, cytogenetic, and molecular studies in relation to the short arm of the X chromosome (Xp). Steroid sulphatase (STS) activity was found to be completely deficient in all affected members of the family. Prometaphase chromosome analyses of two obligate heterozygous women and one affected male showed normal karyotypes. Xg blood group antigen analysis and molecular studies employing cloned DNA sequences from the distal segment of the Xp (probes RC8, 782, dic56, and M1A), did not provide evidence for deletions or rearrangements of the X chromosome. The linkage analysis showed no crossovers between the disease, Xg, and DXS143, the locus defined by probe dic56, thus suggesting the possibility of a linkage between these two markers of the distal segment of Xp and the X-linked ichthyosis, hypogonadism, and anosmia syndrome.