Health-related quality of life and coping strategies of children after treatment of a malignant bone tumor: a 5-year follow-up study

PURPOSE: This study was designed to evaluate the development of health-related quality of life (HRQoL) and coping strategies of children and young adults, who have undergone surgery for a malignant bone tumor in childhood. PATIENTS AND INSTRUMENTS: In this single center follow-up study 20 patients were included. The patients were tested 3 and 8 years after treatment. At the 3-year mark the parents participated as well. To measure the HRQoL and coping strategies the TACQOL and the TAAQOL questionnaires and the Utrecht Coping List for Adolescents (UCLA) were used. All measurements were compared to a control group of healthy peers (n = 1,122 and n = 272, respectively). RESULTS: At the first measurement (3 years after treatment) both the study patients and their parents reported significantly lower HRQoL scores on two domains: motor functioning and autonomy (P < 0.05). In addition parents reported their children to have significantly lower HRQoL scores on cognitive functioning and experiencing positive emotions. Five years later (8 years after treatment) the young adults reported comparable HRQoL on motor functioning and autonomy, and significantly higher HRQoL scores on cognitive functioning, social contacts and negative emotions (less depressive moods). With regard to coping strategies no significant differences between the two measurements in the study population and the reference group were found. CONCLUSIONS: Three years after surgery for a malignant bone tumor, patients and their parents reported lower HRQoL scores on different domains compared with a reference group. Eight years after surgery the young adults surprisingly reported comparable or higher HRQoL scores. These patients treated for bone cancer were able to adapt well after treatment and showed no long-term emotional or social problems.     

The Minneapolis-Manchester Quality of Life instrument: Reliability and validity of the Youth Form

OBJECTIVE: Improvements in survival after childhood cancer have increased emphasis on health-related quality of life (HRQoL) of survivors. We developed the Minneapolis-Manchester Quality of Life-Youth Form (MMQL-YF) as a standardized patient self-report instrument designed to assess HRQoL in childhood cancer survivors between the ages of 8 and 12 years. STUDY DESIGN: To validate the instrument, the MMQL-YF was administered to 643 children (481 healthy, 162 with cancer). Factor analysis was conducted to refine the instrument, and Cronbach's alpha coefficient was used to measure its internal reliability. Known-groups validity was determined by comparing healthy children with those with cancer. Construct validity was studied by a comparison of similar domains in the MMQL-YF and the Child Health Questionnaire (CHQ). Stability was tested by re-administration of the MMQL-YF 2 weeks later. RESULTS: Internal consistency reliability was in the acceptable range for this instrument. The MMQL-YF was able to distinguish between known groups, and its scales correlated highly with similar CHQ domains. Test-retest reliability showed that the instrument was extremely stable in all scales tested. CONCLUSION: Data provide evidence for the validity and reliability of the MMQL-YF as a comprehensive, multidimensional, self-report instrument for measuring HRQoL among childhood cancer survivors.     

Adult Heights of 258 Girls with Turner Syndrome on Low Dose of Growth Hormone Therapy in Japan

Growth hormone (GH) therapy was approved in 1999 for only GH-deficient Turner syndrome (TS) in Japan. It was subsequently approved for all cases of TS regardless of GH secretory status since 1999. The dose of GH is 1.0 u (0.35 mg)/kg/wk at present, but it was 0.5 u (0.175 mg)/kg/wk before 1999. The adult height in patients with TS on the dose of 0.5 u/kg/wk was studied from the report on of Foundation for Growth Science in 2000. GH therapy was registered for 920 cases, and 258 cases reached adult height. The mean adult height was 145.7 cm. The adult height in patients with TS without GH therapy was reported to be 138 cm in Japan. Thus, the height gain by GH treatment was 7.7 cm. The mean age at the start of GH therapy was 12.0 yr old. The mean duration of GH therapy was 5.6 yr. The mean age at the start of estrogen therapy was 17.0 yr old. Patients in Japan were older at the start of GH and estrogen therapy than in the US and Europe at that time. The adult height and gain of height SD were not correlated with age at the start GH therapy in this study. This may be the result of the older age at the start of GH therapy and the low dose of the GH therapy. Patients are beginning to start GH therapy at a much earlier age and the dose has been doubled in Japan. We expect that the recent data concerning adult height in the patients with TS after GH therapy will improve better than this report.     

253例中国Turner综合征患者的自然生长曲线

目的制作中国人Turner综合征（TS）自然生长曲线。研究Turner综合征患儿自然生长规律。方法对全国5省市8所医院确诊的253例TS患者治疗前的身高、体重和骨龄进行观测。同一患者的2次测量值间隔至少超过1年才作为2例次参数计,共取得289个身高值和106个骨龄值。身高值经曲线参数估计法绘制曲线并与正常女孩生长曲线进行比较。结果患儿平均出生身长为(47.2±2.5)cm,身长标准差得分（HtSDS）为-1.52。3岁至13岁各年龄组患儿平均身高及其HtSDS值随年龄增大与正常值差距增大,HtSDS从3岁的-2.11降至13岁的-4.83,患儿平均身高与同年龄正常身高均数之差由3岁的8.03cm增加至13岁的27.89cm,从13岁起逐渐减少至20岁的18.87cm。成年身高为(140.0±7.9)cm。8岁前TS患儿生长曲线     

Anabolic steroid and gonadotropin releasing hormone analog combined treatment increased pubertal height gain and adult height in two children who entered puberty with short stature

We studied the effect of gonadal suppression treatment in combination with anabolic steroid on pubertal height gain and adult height in two children who entered puberty with short stature. Patient 1 was a female with idiopathic short stature. She received combined treatment with an anabolic steroid (stanozolol) and a gonadotropin releasing hormone analog (leuprorelin acetate). Her pubertal height gain was 28.5 cm, which is greater than that in normal height girls (20-25 cm). Patient 2 was a male with Aarskog syndrome. Although his growth hormone (GH) secretion was normal, he received GH treatment. Since GH administration did not accelerate his growth, he received combined treatment with stanozolol and leuprorelin acetate. His pubertal height gain was 27.0 cm, which is greater than that observed in GH deficient boys treated with GH alone (21.9 cm). Combined treatment with stanozolol and leuprorelin acetate appears to be effective in increasing pubertal height gain and adult height in children who enter puberty with short stature.     

Health-related quality of life in paediatric patients with inflammatory bowel disease related to disease activity

Aim: Impaired health‐related quality of life (HRQoL) and an increased risk of psychosocial problems may encounter children and adolescents with inflammatory bowel disease (IBD). Generic HRQoL questionnaires, 15D designed for subjects over 16 years of age, 16D for adolescents aged 12–15 and 17D for younger children, allow comparison to healthy peers and have not been used in children with IBD before. Further, in paediatric IBD patients, HRQoL has not been related to disease activity. We evaluated the applicability of 15D, 16D and 17D questionnaires in the paediatric IBD population and examined how HRQoL is influenced by changes in clinical activity of IBD. Methods: The study subjects recruited at their scheduled, routine appointment in the outpatient clinic of the children's hospital completed the HRQoL questionnaire at baseline and again after 3–5 months. Disease activity was estimated by a three‐level scale. The HRQoL of the study population was compared with that of the age‐standardised general population. Results: Fifty‐five children, aged 7–19 years, were recruited. The HRQoL scores strongly correlated with the activity of the disease (P < 0.001). The two oldest age groups with IBD had lower HRQoL scores than age‐standardised peers (P= 0.001/0.04). There was no gender difference in HRQoL scores. Conclusions: IBD has a considerable impact on the HRQoL of children and adolescents. The generic HRQoL instruments used appeared to be promising tools for examining HRQoL in paediatric IBD patients in different age groups, but larger studies to establish their usefulness in the follow‐up of young patients are still warranted.     

Improved final height in Turner's syndrome following growth-promoting treatment at a single centre

AIMS: To examine the final height (FH) outcome of girls with Turner's syndrome (TS) treated at a single Scottish centre (Glasgow group), to compare it with an earlier national analysis (Scottish group) and to suggest reasons for any change. METHODS: Retrospective growth and treatment data for 29 Glasgow patients were compared with those of 26 Scottish patients. RESULTS: Age at GH start (mean +/- SD) was 10.1 +/- 2.6 vs 12.1 +/- 1.7 y (p < 0.01) in the Glasgow versus Scottish groups, with overall duration of treatment 6.2 +/- 2.4 vs 3.7 +/- 1.1 y (p < 0.001) and years of GH treatment before pubertal induction 2.7 +/- 2.8 vs 0.3 +/- 0.8 y (p < 0.001), respectively. Pubertal induction was at a similar age: 12.7 +/- 1.8 vs 12.8 +/- 1.8 y (ns). FH was 151.1 +/- 4.6 cm in the Glasgow group compared with 142.6 +/- 5.6 cm in the Scottish group (p < 0.001), with FH - projected adult height (PAH) 5.7 +/- 4.6 cm vs 0.6 +/- 3.6 cm (p < 0.001), respectively. Univariate analysis of the Glasgow group's FH - PAH with a number of growth and treatment variables identified no statistically significant relationships. CONCLUSION: This group's improved FH and FH - PAH, relative to an earlier sample, are attributed to the introduction of GH treatment from a younger age and for longer, overall and before pubertal induction. In addition, the authors believe that compliance with treatment has been enhanced by this single centre's dedicated Turner clinic and the efforts of its established "growth team". These data demonstrate that a favourable FH can be achieved using a safe and financially viable dose of GH, while inducing puberty at a "normal" age.     

雌激素替代诱导Turner综合征患儿乳房和子宫发育临床观察

目的　观察以雌激素替代诱导Turner综合征患儿乳房和子宫发育进程的规律,探究获得模拟正常青春发育进程的疗效与雌激素剂量和疗程的关系。方法　2005年1月至2015年12月期间,对就诊于中山大学附属第一医院儿科57例无青春发育或发育停滞的Turner综合征患儿,按国际指南方案治疗,以雌激素小剂量开始,逐步递增。回顾性分析雌激素剂量调节方案与乳房Tanner分期和子宫发育进程的关系。结果　57例Turner综合征患儿开始雌激素替代治疗年龄为15.00（14.25,16.87）岁,追踪时间2.07（0.62,3.06）年。（1）乳房发育：追踪年限内达到B2、B3、B4和B5期所需时间分别为0.29 （0.25,0.33）,0.75 （0.46,1.08）,2.20 （0.92,3.08）和3.67 （1.71,4.44）年。（2）子宫发育：雌激素替代治疗前,Turner综合征患儿子宫容积0.51（0.14,0.86） mL,长径1.89（1.23,2.18） cm。替代后乳房达B2期时,雌激素剂量≤0.5 mg/d组与＞0.5 mg/d组的子宫容积和长径差异无统计学意义。B3期时,雌激素≥1.0 mg/d组的子宫参数均大于雌激素＜1.0 mg/d组。B4期时,雌激素≥1.5 mg/d组的子宫容积较＜1.5 mg/d组子宫容积大。结论　Turner综合征患儿接受雌激素替代治疗后,乳房发育进程可接近正常。子宫发育随乳房Tanner分期进展。在乳房发育达B2期后,子宫发育进程对雌激素依赖性增加。雌激素替代治疗时,起始可予小剂量,达B2期后可适当加大剂量并递增,以加速子宫发育。     

Psychometric properties of the Swedish PedsQL, Pediatric Quality of Life Inventory 4.0 generic core scales

Aim:  To study the psychometric performance of the Swedish version of the Pediatric Quality of Life Inventory (PedsQL) 4.0 generic core scales in a general child population in Sweden.
Methods:  PedsQL forms were distributed to 2403 schoolchildren and 888 parents in two different school settings. Reliability and validity was studied for self-reports and proxy reports, full forms and short forms. Confirmatory factor analysis tested the factor structure and multigroup confirmatory factor analysis tested measurement invariance between boys and girls.
Results:  Test-retest reliability was demonstrated for all scales and internal consistency reliability was shown with α value exceeding 0.70 for all scales but one (self-report short form: social functioning). Child-parent agreement was low to moderate. The four-factor structure of the PedsQL and factorial invariance across sex subgroups were confirmed for the self-report forms and for the proxy short form, while model fit indices suggested improvement of several proxy full-form scales.
Conclusion:  The Swedish PedsQL 4.0 generic core scales are a reliable and valid tool for health-related quality of life (HRQoL) assessment in Swedish child populations. The proxy full form, however, should be used with caution. The study also support continued use of the PedsQL as a four-factor model, capable of revealing meaningful HRQoL differences between boys and girls.     

Management of puberty in growth hormone deficient children

The pubertal growth spurt accounts for approximately one-eighth of adult height and is regulated by complex hormonal interactions involving the somatotropic and gonadal axes. The observation that children with growth hormone deficiency (GHD) may fail to achieve an appropriate pubertal growth spurt led to the development of strategies to optimize GH therapy during puberty. In one strategy the dosage of GH is increased during puberty to support pubertal growth and in keeping with the physiological increase in serum levels of the hormone seen at that age. A different approach is to combine a GnRH analog (GnRHa) to GH to stop pubertal development, delaying epiphyseal fusion and prolonging peripubertal growth. Both strategies require caution. As regards the first strategy, too high doses of GH may shorten the pubertal time for growth; we found a small, nonsignificant, improvement in final height by increasing the dose by less than half. Preliminary results on the second strategy are more encouraging. However, manipulation of puberty should be limited to selected patients who show a statural height SDS for bone age unfavorable in terms of height prognosis.     

Trends in GH use in a Turner syndrome natural history study

The present observations are derived from 273 girls and women aged 7-40 years participating in the National Institutes of Health natural history study of Turner syndrome (TS) in the interval 2001-2011. There was a higher percentage of GH use among individuals in the pediatric age group (7-17, n = 118, 83%) compared to young adult women with prior GH use (18-40, n = 155, 61%). The major factor in this divergence seems to be a trend toward earlier diagnosis of TS in the younger age group. We find a striking association between history of GH use and lower total body and abdominal fat mass in young adults with TS approximately one decade after discontinuation of GH treatment. The interpretation of this observation is limited by the fact that our study subjects were not randomly assigned to GH treatment. There may be a bias involving poor health care, childhood obesity, delayed diagnosis, absent GH treatment and persistent adult obesity. Further studies on the socioeconomic factors implicated in patterns of GH use and non-use for girls with TS are needed to illuminate this important issue.     

Long-term psychosocial consequences of hormone treatment for short stature

AIM: To examine psychosocial functioning of young adults with idiopathic short stature or short stature born small for gestational age after growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) treatment in early adolescence or no intervention. METHODS: Thirty young adults (18 treated, 12 untreated; age 17-23 years; on average 5.5 years after the end of treatment) completed questionnaires regarding perceived competence and psychological distress. They and their parents were interviewed on social circumstances, height-related psychosocial stressors and parental worries about prospects in society. RESULTS: Height gain was on average 2.3 cm more for the treated than for the untreated group. On none of the psychosocial variables differences were found between treated and untreated participants. Compared to Dutch population norms, psychological and social functioning was normal. CONCLUSION: GH/GnRHa treatment, with arrest of pubertal development and lower than expected effects on final height, is not observed to lead to long-term negative or positive effects. Both treated and untreated participants go well through the psychosocial transition period of young adulthood. This suggests that, in the long term and independent of hormone treatment, adequate psychosocial adjustment is expected in case of short stature.     

Growth and pubertal development in patients with meningomyelocele: a retrospective analysis

Our retrospective analysis of growth and pubertal development includes 109 children and adults with meningomyelocele (MMC) (52 M, 57 F) aged 3.2-21.0 years (median 8.9 years). Anthropometric data, growth-retarding factors and data on pubertal development were analysed in comparison to the normal population using standards from Prader et al. (1). The results (mean ± SD) were as follows. Fifty patients (46.8%) had short stature (height SDS for chronological age (SDS CA)< -2). The supine length was influenced by the level of the lesion (height SDS CA: ≥ L2 -3.13 ± 1.62, ≤ S2 -0.46 ± 1.27), ambulatory status, skeletal deformities and pubertal stage. The mean adult height ( n = 15, age 16.1–21.0 years) measured 141.3cm for women (height SDS CA -3.83 ± 1.79) and 159.2 cm for men (height SDS CA -2.27 ± 1.81). In 82.6% of the subjects ( n = 90), arm spans were within the normal range. Reduced arm spans (SDS < -2) as found in 19 patients (17.4%) with short stature (mean height SDS CA -3.29 ± 1.29) may be caused by factors other than neurological lesions and skeletal deformities, and require further endocrinological studies. Out of 27 pubertal patients, central precocious puberty was diagnosed in five girls. The stages of puberty in MMC girls developed earlier than expected for the age-related group.     

Pubertal growth and development in cystic fibrosis: a retrospective review

AIM: Normal growth patterns are seen throughout the first decade in children with cystic fibrosis (CF). Growth in the second decade is, however, less satisfactory and may reflect pubertal delay. This study was performed to assess the extent of pubertal delay, to examine factors that influence the timing and magnitude of the pubertal growth spurt, and to establish whether the final height for most CF patients differed significantly from the normal population. METHODS: Thirty subjects (16 male) attending a single centre were studied. Peak height velocity (PHV), final height and ages when achieved were compared with population norms. Outcome data were correlated with disease severity using Shwachman and Chrispin-Norman scores and forced expiratory volume in 1 s. RESULTS: PHV was significantly later in both genders in this CF population compared with Tanner and Whitehouse standards: boys 14.6 y (95% confidence interval (95% CI) 12.4-16.8, p < 0.01) and girls 12.6 y (95% CI 10.5-14.7, p < 0.01). Mean PHV was also lower in both genders (boys 7.7 cm y(-1) and girls 6.4 cm y(-1), both p<0.001). However, final heights did not differ significantly from Freeman standards (height standard deviation scores: males--1.2, females--0.1); 52% of final heights equalled or exceeded the mid-parental centile. CONCLUSION: CF patients showed suboptimal PHVs with a later pubertal growth spurt influenced by disease severity, but eventually achieved a normal final height.     

Differences in somatomedin-C between short-normal subjects and those of normal height

We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive.     

Disturbed Pubertal Growth in Girls after Acute Leukaemia: a Relative Growth Hormone Insufficiency with Late Presentation

Long-term follow-up of growth and development after acute lymphoblastic leukaemia (ALL) in childhood has previously been limited to the prepubertal period. This study describes pubertal growth, final height and the spontaneous secretion of GH in girls treated for ALL, including CNS irradiation with 24 Gy. Ten girls, treated earlier for ALL, experienced the menarche at a mean age of 12.2 years. This is significantly earlier than the mean for Swedish girls. Prepubertal growth was near normal after the end of therapy for leukaemia. Mean final height was -1.7 SD, which is 1.5 SD less than at onset and 1.0 SD less than 1 year after the end of treatment. Thirteen other girls had a blunted spontaneous secretion of GH, several years after treatment for ALL: there was no increase in GH secretion during puberty. These results suggest that girls who have been treated for ALL, including CNS irradiation, have a relative GH insufficiency. This insufficiency becomes obvious only when the girls cannot respond to the increased need for GH during the pubertal spurt.     

Reduced spontaneous growth hormone secretion in patients with Turner's syndrome

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 peaks < 8 microg/l after pharmacological tests) and both groups were lower (p < 0.0001 and p < 0.0005, respectively) than MGHCs of 27 short normal girls (GH peak > 8 microg/l). MGHC of the patients with TS was negatively correlated (p < 0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE < 20% was significantly higher (p < 0.02) than that of the TS patients with BWE > 20%, but again did not differ from that of the GH-deficient patients and was lower (p < 0.001) 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 tests < 8 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.     

Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone

OBJECTIVES: To investigate the effects of growth hormone (GH) therapy on craniofacial growth and body proportions in growth hormone deficient children. STUDY DESIGN: By using a cross-sectional study design, we investigated GH effects on craniofacial growth with photographic facial morphometrics, head circumference, and hand and foot size in 52 children with GH deficiency (GHD) treated with GH (0.27 mg/kg/wk) for 0.19 to 15.5 years, compared with untreated children with GHD and normal first-degree relatives. To detect disproportion and to correct for stature, age and height age (HA) SD scores were analyzed. RESULTS: Untreated subjects with GHD had retarded facial height and width (P values=.001) compared with normal controls; small head circumference for age and HA (P=.001); small hands for age (P<.001) that were large for HA (P=.003); and small feet for age (P<.001) that were normal for HA. When compared with normal controls, GH-treated subjects had proportional facial heights but narrower facial widths. Head circumference, however, increased disproportionately to height (P=.001), becoming large for stature, and increasing with duration of therapy and cumulative GH dose (P<.001). Hands and feet grew proportionately to height. CONCLUSION: Growth hormone treatment with conventional doses partially corrects craniofacial deficits and does not adversely affect hand and foot growth but appears to result in excessive head circumference growth.     

Effects of growth hormone (GH) and insulin-like growth factor-I therapy in patients with gene defects in the GH axis

We report on four patients (3 F) who were diagnosed as having either a 6.7 kb GH1 gene deletion, a GH1 signalling peptide mutation, or a GH receptor mutation, with particular regard to treatment modalities (GH, rhIGF-I) and final height. Patients with GH1 gene defects developed anti-GH antibodies (GH-Ab) following GH treatment. Surprisingly, growth response to GH was unrestricted in one girl, who reached a final height within her target height range, whereas her cousin with the identical genetic defect responded far less favourably. Variability in the growth inhibiting potency of GH-Ab may therefore depend on genetic disposition, specific epitopes, or induction of immunological tolerance. Growth response during rhIGF-I treatment carried out in three of the patients was moderate, but pubertal development and bone age acceleration occurred in the two patients treated at pubertal age. GH resistance, either caused by GH-Ab or GH receptor mutations, is still difficult to treat and results in a heterogeneous outcome.     

Treatment of precocious puberty in two patients with Turner mosaicism

Turner's syndrome (TS) is clinically characterized by reduced growth, ovarian dysgenesis and infertility. The majority of patients with TS do not undergo spontaneous pubertal development. We report two patients with mosaic Turner karyotype who experienced precocious pubertal development. The first patient responded well to LHRH analog treatment and now has regular menses and has nearly achieved her target height. The second patient was treated with both LHRH analog and recombinant growth hormone. LHRH analog delayed puberty for the patient and the recombinant growth hormone increased the patient's predicted height from 145 cm to 158 cm. This report emphasizes that the treatment goals and modalities of patients must be tailored to the individual to optimize pubertal and growth outcomes.