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Aim: To determine whether children with psychosocial short stature attain their genetic height potential., Methods: We report on 18 children (10 girls, 8 boys) diagnosed by a multidisciplinary team as having psychosocial short stature. All the children had had some kind of change in their environment (9 were separated from their families), and increased their mean height velocity standard deviation score (SDS) from -0.7 (1.3) to +3.6 (4.8) (p < 0.005) as well as their height SDS from -3.0 (0.3) to -2.6 (0.9) in the first year after the change. All the patients were postpubertal and had reached their near final height (mean age, 20.0 y; range, 16.0-23.3)., Results: Only 3 out of 18 had a greater final height than the mid-parental target height, 14 out of 18 had a near final height within the mid-parental target range (95% tolerance limits of the mid-parental height (+/- 2 SD = +/- 10 cm). Nevertheless, mean final height expressed in height SDS for the whole group was significantly shorter with -2.4 SDS compared with the mean of the mid-parental target height of -1.5 SDS (p < 0.001). Surprisingly, initial catch-up growth did not correlate with final height attainment., Conclusion: The majority of patients will attain a stature within the range of mid-parental target height, although towards the lower limit of this range.

Aim: To examine the relationship between growth hormone (GH) and psychological functioning, especially self-perception and well-being, in 60 prepubertal boys of short stature with a wide range of GH levels., Methods: A comparison was made of the well-being and self-perception of children with GH insufficiency, children with idiopathic short stature (ISS), a normative sample and healthy boys with normal stature., Results: Children with GH insufficiency had a more negative perception of their own physical appearance than the normative sample. They perceived themselves as more alert but also more inhibited than both the children with ISS and the healthy boys with normal stature. In comparison with the healthy boys with normal stature they perceived themselves as having more stability. The parents of the boys with GH insufficiency also perceived their children as being more stable compared with how the parents of boys with ISS perceived their children. To elucidate the effects of GH on psychological functioning a multiple regression analysis was performed., Conclusion: The lower the levels of GH the more inhibited were the boys of short stature, as perceived both by themselves and by their parents. The boys with GH insufficiency had a more negative perception of their physical appearance than the normative sample.

In adults, GHD is a clinical syndrome that occurs in patients with pituitary or hypothalamic disease. It may be asymptomatic or present with relatively nonspecific constitutional symptoms. Most patients have abnormal body composition, consisting of increased fat mass and decreased lean mass. Life expectancy is significantly decreased in hypopituitary patients with GHD, with cardiovascular disease a common cause of death. Treatment with growth hormone reverses abnormalities in body composition and may reduce cardiovascular risk factors; however, the long-term treatment outcomes regarding mortality, the incidence of cardiovascular disease, bone fractures, tumor development, and recurrence are not known. Longer prospective clinical studies are needed. The major manufacturers of growth hormone have initiated postmarketing surveillance databases to monitor the safety of growth hormone treatment.

Barth syndrome (BTHS) is a rare, X-linked, recessive disorder that affects almost exclusively males. It is characterized by short stature, cardioskeletal myopathy, cyclic neutropenia, increased excretion of 3-methylglutaconic acid in the urine, and moderate hypocholesterolemia. The objective of the present study was to assess whether BTHS presents with a cognitive phenotype. Preliminary data were collected from five kindergarten or first-grade boys with BTHS. An abbreviated psychoeducational test battery was administered to each boy, and parents of each boy completed standardized behavior rating scales. Data from 120 boys of similar age or grade level were used for one comparison group; a subset of this sample comprised a comparison group that was individually matched on age and grade level to one of the five boys with BTHS. Preliminary data reflect a higher incidence of cognitive difficulties in boys with BTHS relative to both comparison groups. Boys with BTHS had significantly lower visual spatial skills, but comparable reading-related skills, when compared with either group. Although based on a small sample size, the preliminary data presented in this work are the first indication of a cognitive phenotype associated with BTHS., (Copyright 2001 Wiley-Liss, Inc.)

Objective: Adult growth hormone deficiency (AGHD) is characterized by abnormalities in body composition and a poor perceived quality of life (QoL). Weight-based high-dose growth hormone replacement (GHR) results in improvements in body composition and QoL in AGHD. However, a high patient percentage reported side-effects on high-dose GHR resulting in a high rate of patient withdrawal from growth hormone (GH) treatment. High-dose GH therapy also leads to supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations that have been associated with breast and prostate cancer, raising major concerns over the use of such high-dose GH regimen in AGHD. The aim of this study was to assess the effects of low-dose growth hormone replacement (GHR) on body composition and QoL as early as 1 and 3 months., Study Design: A prospective, open treatment design study to determine the early effects of low-dose GH administration on body composition and QoL. GH was initiated at a daily dose of 0.4-0.5 IU, and titrated up to achieve and maintain IGF-I standard deviation score (IGF-I SDS) between the median and upper end of the age-related reference range., Patients: Forty-six, post-pituitary surgery, severe AGHD patients (22 women), defined as peak GH response < 9 mU/l to provocative testing. The mean age was 50.4 years (range 26-72). Forty-three patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment., Measurements: Body composition and QoL were assessed prior to GHR and subsequently at 1 and 3 months after initiating GHR. Body mass index (BMI) and waist hip ratio (WHR) were calculated from measurements of height, weight, and waist and hip circumference, respectively. Bioelectrical impedance analysis (BIA) was used to determine body fat and lean body mass. QoL was assessed using the disease-specific 'QoL-assessment of growth hormone deficiency in adults (QoL-AGHDA)' questionnaire. Serum IGF-I was measured at each visit to assess the adequacy of GHR., Results: IGF-I and IGF-I SDS increased significantly at 1 and 3 months (P < 0.001) after commencing GHR. The increase in IGF-I (P < 0.05) and IGF-I SDS (P < 0.01) was significant between 1 and 3 months in the absence of any significant increase in GH dose (P = ns) during this period. Eighty-five per cent of patients achieved IGF-I SDS levels between median and upper end of the age-related reference range after 3 months of GHR, and no side-effects were reported during this period. There was a significant reduction in body fat percentage (BFP) from 36.1 +/- 9.1% at baseline to 34.9 +/- 9.3% (P < 0.01) at 1 month and 34.1 +/- 9.2% (P < 0.001) at 3 months. Body fat mass (BFM) reduced from 32.8 +/- 13.6 kg at baseline to 31.9 +/- 13.9 kg at 1 month (P < 0.05) and 31.1 +/- 13.6 kg at 3 months (P < 0.001). These changes in BFP and BFM occurred in the absence of any significant change in BMI and WHR (P = ns). Lean body mass (LBM) was 55.9 +/- 11.1 kg at baseline and increased to 57.1 +/- 11.3 kg after 1 month (P < 0.01) and to 57.6 +/- 11.5 kg (P < 0.001) after 3 months of GHR. Significant improvement was observed in the perceived QoL with the AGHD assessment scores reducing from 13.3 +/- 6.4 to 11.5 +/- 6.6 within 1 month (P < 0.01) and 10.0 +/- 6.6 at 3 months (P < 0.001). There was no significant correlation between improvement in QoL and changes in body fat percentage (r = 0.01 at 1 month and r = 0.12 at 3 months, P = ns) or IGF-I levels (r = 0.04 and r = 0.003, P = ns at 1 and 3 months, respectively). The improvement in body composition and QoL was significant between 1 and 3 months., Conclusions: Low-dose GHR improves body composition and QoL as early as 1 month after commencement and the beneficial effects continue at 3 months. Most importantly, these changes occur in the absence of side-effects. We therefore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of AGHD.

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

Unlabelled: The indications for growth hormone (GH) treatment in non-GH-deficient short children are in debate, with some arguing that this treatment does not belong solely in the medical domain. We describe three different approaches to the issue, and argue that neither a disease-oriented nor client-oriented approach is sufficient. Both lead to withdrawal of medical interventions or to an undesirable application., Conclusion: An approach focusing on suffering as an indication for treatment of short stature is the most appropriate. The challenge is to develop proper tools by which to evaluate suffering and the efficacy of GH treatment in these children in order to relieve or prevent suffering.

Divergent findings on the quality of life (QoL) and the psychosocial functioning of adults treated during childhood with growth hormone (GH) because of GH deficiency (GHD) have been reported. In the present study we evaluated the QoL and the perception of the effect of former GH treatment in Belgian young adults with childhood GHD. Thirty-six patients (22 males) were included in the study. They all were treated during childhood with GH for GHD. QoL was evaluated with a standardised questionnaire: the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Psychosocial functioning, sexual experience and schooling were evaluated by semi-structured interviews and questionnaires. The influence of gender, type of hormone deficiency (isolated GHD vs multiple pituitary hormone deficiencies [MPHD]), age at the start of GH therapy (before 12 yr vs after 12 yr) and the height deficit at the start of GH therapy (< -3 SDS vs > -3 SDS) were studied. In addition, the patients' and parents' perception of height and of the effect of GH treatment was retrospectively evaluated by semi-structured interviews. Age (mean +/- SD) at the time of evaluation was 20.0 +/- 1.3 yr and final height was -0.5 +/- 0.9 SDS, comparable to mid-parental height (-0.6 +/- 0.8 SDS). The QoL-AGHDA score was 9 +/- 6. About half of the patients, especially those in whom GH treatment was started after the age of 12 years, complained of retrospective difficulties with self-confidence and social contact, and about one-quarter of the patients had current difficulties with self-confidence, social contact, contact with the opposite sex and with emotional life. Only 44% of the patients had had sexual intercourse--none of those with MPHD. According to the parents, the patients had and still have more difficulties with self-confidence and social contact than their siblings and/or peers, and they needed and still need more emotional support. In one out of four patients the parents expected difficulties in finding a job, in one out of three patients parents expected difficulties in leaving home or in having a stable relationship. The educational level of patients with a height deficit < -3 SDS at start of GH therapy was lower than in patients with a height deficit > -3 SDS. According to the parents, about half of the patients, especially those with MPHD, had more study problems compared to siblings. In all patients, satisfaction with final height and GH therapy was obvious. In conclusion, the psychosocial outcome of young adults with childhood GHD was more satisfying than in previous studies. This could be due to a more adequate GH treatment with better final height results. Nevertheless, more difficulties with respect to psychosocial functioning were observed in patients with MPHD, in patients in whom GH treatment was started after 12 years of age and in patients with a height deficit < -3 SDS at the start of GH therapy, underlining the need for early diagnosis and treatment of childhood GHD, and of continuing medical follow-up and psychosocial counselling, particularly in these subgroups of patients with GHD.

A major justification of extended indications for GH therapy in conditions with short stature is based on the objective of preventing or alleviating suspected psychosocial maladjustment. Despite more sophisticated research, results are still controversial concerning the actual seriousness of adjustment difficulties in various conditions with short stature, thus making it difficult to determine a patient's need for treatment. This paper discusses different concepts and assessment strategies of "adjustment" as a major source of the apparent heterogeneity among study findings, conclusions and treatment recommendations. A concise framework is developed that identifies and differentiates three hierarchical levels of research on adjustment in conditions with growth retardation: (1) stress exposure due to short stature, (2) quality of coping responses, and (3) occurrence of psychopathology. Choosing a particular research level and its corresponding measures may imply whether a high, medium or very low impact of short stature on adjustment is found, and the need for treatment that is inferred. The integration of these different research approaches within an integrative model may help to resolve apparent inconsistencies among empirical studies and reveal sources of confoundation due to other, short stature independent risk factors associated with the particular underlying growth disorder. The key terms of the suggested model are transformed into a clinical guideline for psychological assessment in patients with growth retardation and into three key criteria for the decision making process on extended indications for GH treatment with respect to the improvement of psychosocial adjustment.

Unlabelled: To assess the effect of therapeutic doses of growth hormone (GH) on the feeding problems, food intake, body fat and mealtime interactions of children with growth disorders, an age-matched group of 46 children with Turner syndrome (TS) or Silver Russell syndrome (SRS) was examined using questionnaire measures and direct observation. The children's body fat was measured using bio-electrical impedance analysis and skinfold thickness measurements. Children receiving GH consumed significantly more energy, protein, fat and carbohydrate than did the children who were not receiving GH, independent of the extent of the child's feeding problems. Children receiving GH had less body fat than did children who were not receiving GH. Children who were not receiving GH distracted their parents from the mealtime significantly more often and received more negative prompting and coaxing from their parents to eat than did children who were receiving GH. This study provides evidence to support the theory that appetite and intake is determined in part by growth and growth potential. Feeding problems seen in children with growth disorders are partly due to parental attempts to impose control over their child's intake, when their child consumes less than the parent believes to be adequate., Conclusion: GH has a significant impact on both the food intake and parent-child interaction at mealtimes of children with SRS and TS.

Eighty-two women who were consuming alcohol while pregnant attended a special clinic at the University Central Hospital, Helsinki with the aim of reducing heavy drinking during pregnancy. The children born to these women were followed up regularly. During their preschool years the children were assessed to have fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, pre- and/or postnatal growth retardation, or they were assessed to have normal cognitive and somatic growth. Of the original children, 70 of 82 could be traced at the age of 12 years. Through semistructured interview and contact with the health and social care authorities, information was gathered about schooling, family structure, whether help had been sought for behavioural difficulties and major adverse events in the family. The longer the intrauterine alcohol exposure and the more severe the diagnosis related to prenatal alcohol exposure, the more often the children required special education, were temporarily or permanently taken into care, and had behavioural problems. There is a considerable need for prolonged multidisciplinary follow-up and support of all children whose mothers have not been able to reduce drinking in early pregnancy, whether or not cognitive disturbances are evident in early childhood.

There is an ongoing debate as to whether symptomatic growth hormone treatment (GHT) in short children without growth hormone deficiency (GHD) is justified, since there is no substitutional indication. The increasing evidence that final height cannot be normalized in these patients (e.g. in Ullrich-Turner syndrome) reinforces this controversy. We have focused on the empirical evidence on the psychosocial and physical meaning of being short in childhood as well as on the underlying assumptions of the different GHT indications. The indication for GHT in patients with non-GHD may be seen as a pharmacotherapeutic intervention in order to prevent the developmental, physical and psychosocial risks associated with short stature. This requires a qualitative shift in methodological assessment with respect to the psychosocial and physical impact of being short as well as of the potential benefit of new treatment indications in terms of a more comprehensive evaluation including health-related quality of life for these patients.

The nutritional condition of children with human immunodeficiency virus (HIV) infection continues to be a problem both in developed and developing countries. HIV-infected children grow below normal standards in both height and weight when compared with HIV-exposed non-infected children. These patterns persist over time. It is possible that acute infectious episodes and increased HIV viral burden contribute to decrements in all growth variables. Potential aetiologies for abnormal growth include inadequate dietary intake, gastrointestinal malabsorption, increased energy utilization and psycho-social problems. It is likely that all these factors contribute to the growth problems of these children to some extent. With the development of protease inhibitor anti-retroviral therapy and highly-active anti-retroviral treatment regimens, children with HIV infection in developed countries are living longer with a chronic illness. New nutritional problems have arisen with the development of the fat redistribution syndrome or lipodystrophy. Emerging problems are now being recognized, with the development of insulin resistance and truncal obesity which may potentially lead to premature cardiovascular disease.

Sotos syndrome is characterized by peculiar facies, prenatal and postnatal overgrowth, and developmental delay. The course of six patients with psychiatric, neurologic, and magnetic resonance imaging evaluations is reported. Three (50%) of the six patients were observed to have a tendency toward aggressiveness, including one who had pyromania.

Objectives: To determine the extent to which childhood short stature is associated with cognitive, behavioural and chronic health problems, and whether these problems could be attributed to recognized adverse biological, psychosocial or psychological factors., Methodology: At their first antenatal session, 8556 women were enrolled in a prospective study of pregnancy. When their children were 4 and 6 years of age, mothers completed a detailed questionnaire concerning their child's health and behaviour. A Peabody Picture Vocabulary Test-Revised (PPVT-R) was completed by the child at 5 years of age. Z scores were used to categorize height measurements in 3986 children. The relationship of these height categories with the child's health, and behavioural and cognitive problems was then examined., Results: No association was found between height and symptoms of chronic disease or behaviour problems in boys or girls. On the unadjusted analysis, mean PPVT-R scores were significantly lower in boys with heights < 3 percentile and 3-< 10 percentile compared with study children between 10 to 90 percentile (P < 0.01). Scores were similarly significantly lower in girls with heights < 3 percentile and 3-10 percentile (P = 0.01). Even after adjusting for psychosocial and biological confounders, short stature remained a significant predictor for lower PPVT-R scores in both boys and girls, although height only accounted for 1.1% of the variance in scores in boys and 0.5% of the variance in PPVT-R scores in girls. Psychosocial factors had a greater role than height in determining PPVT-R scores at 5 years of age., Conclusions: These findings suggest a significant, though small, association between height and PPVT-R scores at 5 years of age, independent of psychosocial disadvantage and known biological risk factors.

In all studies of health-related problems and their effects on well-being, research design issues threaten to compromise the validity of findings. This is particularly so in a longitudinal study, essentially stemming from the tension between maintaining participant compliance and retaining investigator objectivity. Such a tension may be exacerbated where measures of dependent variables such as self-esteem are used alongside the collection of physical data which is essential to the study, as in research into the psychological effects of short stature on children and young people. In this paper one particular project, the Wessex Growth Study, is used to illustrate the common threats to validity, both internal and external, of such research, and to consider future improvements in design. The Wessex Growth Study, set up in 1986, was designed to overcome some of the methodological problems found in earlier research with short stature children. It is following the growth and psychological development through their school years of a cohort of short children (below third centile for height when first identified) and case-matched controls (10th-90th centiles) recruited at school entry (ages 5/6). Findings have generally found only small differences between short and average height children. Though these results so far have mainly been presented cross-sectionally, the young people involved are followed up at 6-monthly intervals for height and other data to be collected, and thus to some extent the study also has the advantages and problems of a longitudinal research design. Using Campbell and Stanley's criteria this article makes clear the strain on both internal and external validity in the study, but argues that these problems are to some extent inherent in all longitudinal psychological research, and are outweighed in the present research by the collection of data on short stature which would not otherwise be available. Future data collection within the study will introduce further improvements in design.

Controlled clinical trials are not always possible or warranted. Other sources of data include observational studies, meta-analyses, expert opinions, subjective judgements, and mathematical/statistical models developed from large databases. Decision analysis is presented as a preferred methodology for analysis in situations of uncertainty, in combination with cost-benefit and cost-effectiveness analyses. Special emphasis is given to quality-of-life considerations in growth hormone (GH) therapy and ways to measure it and express patient preferences.

This paper examines the role of parents' attitudes and preferences regarding growth hormone therapy for childhood short stature. Four main questions are addressed. First, what are the demographic characteristics of families seeking medical advice for their child's short stature? Second, what are parents' attitudes towards short stature? Third, what are parents' treatment preferences (i.e. what characteristics of growth treatments are important to parents)? Finally, how do the attitudes of parents affect physician decision making? Several studies are reviewed and data are presented to answer these questions.

Intrauterine growth retardation (IUGR), defined as birth weight and/or length less than 3rd percentile (P) or less than-2 standard deviations (SD), concerns about 3% of newborns. About 85% born IUGR show spontaneous postnatal catch-up to a height > P3 or > -2 SD during the first two years of life. After the age of 4 year, the children without catch-up will remain short up to final height. Classical growth hormone (GH) deficiency usually does not seem responsible for the absence of catch-up in those children. A two-year GH therapy at supraphysiological doses increases growth velocity. The effect of this treatment on final height remains to be studied, as well as optimal treatment's modalities. Attention should be paid on the possible side-effects. Finally, the evaluation of the psychological impact of GH treatment will be critical.

Metaphyseal growth arrest lines are seen in children who experience significant physical stress such as infection or malnutrition over a sufficient period of time. These lines have not been reported previously in children with psychosocial short stature (PSS). Two boys and a girl with PSS with metaphyseal growth arrest lines on skeletal radiographs at the time of maximal stress in their homes are described. All three had reversible growth hormone insufficiency during admission, which is pathognomic for PSS. Multiple growth arrest lines in the distal end of the radius or vertebrae should alert clinicians to an alternative diagnosis in a child with growth hormone insufficiency. This may provide a clue to the diagnosis of occult PSS.

Background: Approximately 39% of children aged <5 y in developing countries are growth retarded (stunted) and many have poor mental development and behavioral abnormalities. Animal research suggests that an altered stress response may contribute to the negative outcomes following undernutrition., Objective: We tested the hypothesis that stunted children have higher salivary cortisol concentrations and heart rates and altered behavior when compared with nonstunted children when social background was controlled for., Design: We compared 30 stunted with 24 nonstunted children, all of whom were 8-10 y old and lived in the same poor areas of Kingston, Jamaica. All subjects were participants in a prospective, longitudinal, case-control study of children who were stunted in early childhood. We administered a test session (including psychologic and physical stressors), measured baseline and response levels of salivary cortisol and heart rate, and observed behavior., Results: Compared with nonstunted children, stunted children had higher salivary cortisol concentrations (P = 0.007), had higher heart rates during the psychologic test session (P = 0.03), exhibited enhanced cardiovascular responsivity to a physical stressor (P = 0.04), vocalized less, were more inhibited, and were less attentive. After birth weight or social background and maternal and child intelligence quotients were controlled for, the differences in cortisol concentration and cardiovascular reactivity remained significant., Conclusions: Our findings suggest that consistent growth retardation since early childhood affects physiologic arousal, which, we speculate, may contribute to the poor cognitive functioning and immune responses of stunted children and the relation between adult short stature and increased cardiovascular risk.

A summary of the majority of the available uncontrolled studies of 322 children with idiopathic short stature treated with growth hormone showed that the final height attainment over predicted adult height was only +2.85 cm (+0.49 SD score). Furthermore, a summary of seven studies reported that the spontaneous outcome in children with untreated idiopathic short stature was more than +1 SD score in final height compared to height at presentation; patients with delayed puberty spontaneously gained more than +2 SD score as adults. Recent reevaluations have concluded that short stature is not associated with clinically significant psychologic morbidity, and the psychologic outcome in response to growth hormone treatment of the short normal child showed no discernable difference in psychologic benefit, despite a difference in height gained. A recent editorial has strongly advised against the expanded use of growth hormone in the normal short child.

We present the most extensive neuropsychological and language assessment yet reported of patients diagnosed with Floating-Harbor Syndrome (FHS), a rare genetic condition characterized by dysmorphid figures, short stature, and speech-onset delay. This is also the second reported occurrence of both a mother and daughter with FHS. Whereas the child demonstrated gross deficits in verbal expression, speech and language problems were largely ameliorated in the mother. Neuropsychological assessment also revealed a strikingly similar pattern of cognitive problems additional to language dysfunction, including difficulties with attention, mathematical, and visuospatial abilities. A mood disorder continued to be quite disabling for the mother.

Objective: To present longitudinal data on the psychological profile of a cohort of girls with and without Turner syndrome (TS) treated for 3 years with growth hormone (GH)., Methods: Among a sample of 283 children with short stature, 37 girls with TS were recruited at 27 US medical centers. Of the original cohort, 22 girls with TS, 13 girls with isolated growth hormone deficiency (GHD), and 12 girls with idiopathic short stature were followed through 3 years of GH therapy. All were school-age, were below the 3rd percentile for height, had low growth rates, and were naive to GH therapy. Psychological tests (the Wide Range Achievement Test and the Slosson Intelligence Test) were administered to the clinical groups within 24 hours of their first GH injection and yearly thereafter. Control subjects were 25 girls with normal stature matched for age and socioeconomic status, who were tested only at baseline. One parent of each subject also completed the Child Behavior Checklist for that subject., Results: At baseline, the clinical groups had more internalizing behavioral problems, had fewer friends, and participated in fewer activities than did the control subjects. The groups did not differ in mean IQ or academic achievement, but the TS group did have more problems in mathematics achievement. Height and growth rate significantly increased in the clinical groups over the 3 years of GH therapy, but IQ and achievement scores did not. Significant linear reductions were noted in both Internalizing and Externalizing Behavior Problems after GH treatment, with the TS group having fewer behavior problems before and after GH treatment than did the GHD-idiopathic short stature group. Decreases in specific Child Behavior Checklist subscales, including attention, social problems, and withdrawal, also were seen in the clinical groups after GH therapy., Conclusions: The comprehensive treatment of girls with TS should include educational and behavioral interventions in addition to traditional medical therapies.

The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0) y, and 25.7 (3.5) y of the control subjects (p < 0.001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0.001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3 (5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.

Recent studies report comparable psychosocial adaptation in children with or without a growth disorder. These findings may be due to a general lack of sensitive and specific techniques for analysing and comparing their respective qualities of life. In this study we present a new questionnaire for parents of short-statured children. We suggest both a qualitative and quantitative approach providing specific information about the relative extent of individual stress factors and sources of help. The parents of 442 children with growth retardation resulting from different aetiologies completed the questionnaire. A principal component analysis of the scaled items revealed four dimensions of psychosocial adaptation; suffering, future anxieties, behavioural problems and coping efforts. The index of internal consistency reliability was sufficient for all scales. The comparison of two selected growth disorder groups (achondroplasia versus growth hormone deficiency) demonstrated growth disorder-specific but not very different profiles of psychosocial adaptation. The qualitative analysis revealed a shift in the stress factor patterns (achondroplasia, more physical restrictions). These findings give evidence for both the specificity and construct validity of the new instrument. Therefore, we may conclude that this questionnaire is a helpful method in attaining growth disorder-specific information about individual stress factors, resources and psychosocial adaptation.

We describe 65 children (32F, 33M) with psychosocial short stature from 51 families. Average age was 6.6 years (range 0.9-16.5) and all but five were prepubertal. 67% of the patients lived in families with three or more children, but in 73% of cases the patient was the first or the second born child. 45% of the parents were divorced and in 31% of the families the father was unemployed. In 56 children, the birth weight was known and in only 29% was it above 3000 g; 21% were premature, 29% had features of low birth-weight syndrome (including four with Russell-Silver syndrome). Average birth weight was 2786 g (range 1650-4676). In all patients, the predominant reason for referral was growth failure. In 28% an environmental aetiology was suspected and in a further 29%, social or emotional problems were known to the referring physician but not suspected as the aetiology of the growth failure, despite social services involvement in 60% at the referral to our unit. At initial presentation in our clinic, we found additional features leading to the suspicion of psychosocial short stature; 54% abnormal eating pattern, 42% behaviour problems, 26% encopresis, 18% nocturnal enuresis and 12% inappropriate urination. During the observation period of a mean of 3.7 years, 27 (41%) of our patients were found to have been sexually or physically abused. In these 27 children hyperphagia, bizarre eating habits, behaviour problems, soiling and nocturnal enuresis were more common.

Children of constitutionally tall stature may experience serious problems related to their height. Treatment with high dose sex steroids may be considered in order to limit final adult height. Prediction of adult height plays a central part in the management of children of tall stature. Various aspects of height prediction in children of tall stature are discussed. The height reducing effect varies between studies from 2 to 10 cm. Recently, in a large Dutch study the mean effects of therapy were 0.7 and 2.4 cm for boys and girls respectively. The effect depended on the bone age at start of treatment. Beyond a critical bone age of about 14 years treatment had no effect. Minimal age for intervention is 9.5-10 year for boys and 9.0-9.5 year for girls. Recommended treatment for boys is 250 mg testosterone esters i.m. per week and for girls ethinyloestradiol orally 200 micrograms per day in combination with medroxyprogesterone or dydrogesterone (both 5-10 mg per day) during the first 12-14 days of the cycle. Treatment has to be continued until complete closure of the epiphyses. While side effects during hormonal therapy are frequent, they are mostly temporary and mild and seldom lead to cessation of therapy. So far there have been no indications of adverse effects on, for instance, gonadal function.

Growth and psychological functioning were studied in 30 patients with renal failure over a two year period following the offer of growth hormone treatment for significant short stature. Parents' concerns about growth decreased significantly during the study. Twenty eight parents (93%) accepted growth hormone treatment; most (74%) were satisfied with it and would opt for it again (89%). The views of these parents were unrelated to growth outcome in their child. This suggests that the positive responses were related more to the effort to improve growth than to any objective treatment success. In contrast children's reduction in concern about growth, satisfaction with treatment (36%), and decision to opt for growth hormone again (50%) were all significantly related to improvement in growth. Parents' reports of non-compliance increased significantly from 41% at 1 year to 91% at 2 years in the group as a whole. No significant changes were identified in maternal mental distress and no additional costs to the psychological health of the children seem to have resulted from the introduction of growth hormone treatment. A group of children was identified who accepted treatment but had continued poor growth. These appeared to be at particular risk of both physical problems and associated or consequent psychological difficulties.

The use of (costly) growth hormone (GH) treatment in short children is often justified by the assumption that short stature considerably reduces quality of life in adults. We tested this assumption in 5 groups of short adults: 25 patients with isolated GH deficiency; 17 male patients with childhood onset renal failure; 25 women with Turner syndrome and 26 patients who were presented as a child to a paediatrician for idiopathic short stature. A group of 44 short individuals with presumably idiopathic short stature, who had not been presented to a paediatrician for short stature, was sampled from the general population ('normal shorts'). We measured quality of life in terms of socio-economic variables, the Nottingham Health Profile and time trade-off. The mean height of most groups was close to the 3rd percentile. The chance of having a partner was low for all groups, except for the normal shorts. Problems with job application were only reported in Turner syndrome. The scores on the Nottingham Health Profile were all within the normal range, but GH-deficient adults had a higher score on the domain energy than normal shorts. Women with Turner syndrome, individuals with renal failure, and those with idiopathic short stature had a wish to be taller, with an estimated reduction in quality of life of 2-4% (time trade-off). As the normal shorts did not show any sign of a reduced quality of life, we falsify the assumption of a direct relation between short stature and quality of life. The complaints of patients with idiopathic short stature around the 3rd percentile seem to be the result of unsuccessful coping strategies.

Growth failure remains a major complication of chronic renal insufficiency in children, which greatly affects their quality of life. Based upon the data published in the literature it appears that growth hormone therapy improves growth in these children, with little secondary effects. However, some uncertainties persist concerning the safety and efficacy of this therapy, so that careful evaluations must continue.

Unlabelled: In 135 women and 85 men who initially presented for tall stature, the outcome in treated (56 women and 33 men; cases) and untreated (controls) was investigated. At the time of height prediction, cases were significantly taller (P < or = 0.03) than the controls, they had higher target heights (P < 0.001) and adult height predictions (P < 0.001) (according to Bailey and Pinneau) compared to the controls. Bone age (according to Greulich and Pyle) and chronological age were well matched in both groups. Final height was measured after cessation of growth at a mean age above 21.5 years. The final height prediction according to Bailey and Pinneau (BP method) overestimated the final height in controls. The mean error of estimation was -0.14 cm (+/- 3.10) in women, and -1.86 cm (+/- 4.37) in men. Age at the time of prediction did not significantly correlate with the degree of the prediction error. Sex hormone therapy comprised a daily oral dose of 7.5 mg conjugated oestrogens in girls (plus 5 mg dydrogesterone for 10 days a month), while boys received 500 mg testosterone enantate, intramuscularly, every 2 weeks. Therapy was well tolerated. The mean corrected effect of height reducing therapy was 3.6 cm (range: 11.9 cm to -3.3 cm) in women and 4.4 cm (range: 14.2 cm to -5.2 cm) in men. Therapy was significantly more effective when started at an earlier chronological (P < 0.01) and bone age (P < 0.01). The residual mean growth, after therapy was stopped, was 1.8 (+/- 1.6) cm in women and 3.1 (+/- 2.3) cm in men. In men, post-treatment growth was inversely correlated to chronological age (P < 0.01) and bone age (P < 0.05) at the end of treatment, while these correlations were not significant in women. Both groups had a higher educational level than the normal population. Treated tall women reported teasing because of tallness more frequently than controls. In tall men, practical issues such as clothing size predominated. Maximum tolerated height in males was 200 cm and in females 180 cm, thus being nearly analogous to the actual professional criteria for treatment recommendation. A positive attitude to treatment was documented in over 90% of treated individuals., Conclusions: Our results show that the BP method gives acceptable adult height predictions in girls, but less accurate predictions in boys. The treatment with high doses of sex hormones was low effective in both sexes and showed a wide range of response. For success, treatment must be initiated in early puberty and terminated late. The answers to a questionnaire revealed no major psychological or social maladjustment of treated individuals compared to those untreated.

Objective: To assess the psychosocial functioning of adults who were evaluated as children for short stature and were not treated with human growth hormone., Design: Inception cohort study., Setting: Hospital-based pediatric endocrinology clinic., Participants: From 1975 to 1980, medical record review indicated that 181 of the children referred to our clinic for concerns about short stature were non-growth hormone deficient. In 1992 and 1993, we were able to recruit 35 of these patients for a follow-up study. Eligible subjects were at least 18 years of age at the time of follow-up., Main Outcome Measures: Standardized self-report questionnaires assessed various domains of psychosocial adjustment. Also, a brief test of intellectual functioning was administered and subjects underwent a semistructured in-person interview to evaluate pragmatic functioning and experiences associated with short stature., Results: Few significant differences between the study sample and standardization samples were found on measures of psychosocial and intellectual functioning. Within-group childhood height during the first evaluation appointment was not significantly associated with most adult measures of psychosocial adjustment. Shorter adult stature was significantly associated with lower educational achievement, lower self-esteem, and greater emotional distress., Conclusions: The absence of significant psychosocial distress or impairment in these subjects brings into question one basis for hormonal treatment for non-growth hormone deficient short stature; that short stature in childhood is likely to lead to psychological dysfunction in adulthood. The results, however, also suggest that shorter stature in adulthood may constitute a psychosocial stressor, increasing vulnerability across several domains.

Tested for defensive attributional bias in mothers' causal explanations for infant (2-12.5 months) growth deficiency. Mothers of healthy babies (controls; n = 82), growth deficient babies without medical problems (n = 27) and growth deficient babies with mild medical problems (n = 22) rated their levels of agreement with 23 causes of growth problems which were designed to vary in the degree of personal threat to parenting self-esteem. Ratings were completed for the mother's (Own) baby and for a nonspecific (Other) baby. Findings partially support a theory of defensive attributional bias, with higher agreement when causes referred to Other (vs. Own) baby, and lower agreement with family-related than with medical/nutritional causes. Factors that may have influenced material experience of threat and implications of the findings for clinical practice are discussed.

The significance of mild sustained brain injury in the pathogenesis of perinatal brain damage was investigated using serial EEG recordings performed on 102 early preterm infants surviving beyond 2 years of age. Sixteen infants (16%) elicited mild depression of background EEG activities in the neonatal period. Of nine infants with mild depression of prolonged duration (more than 3 weeks), five (56%) were diagnosed as having cognitive impairment in the follow up study. Four showed no signs of cerebral palsy, while one had cerebral palsy. The infants with cognitive impairment showed mild prolonged depressions in background EEG activities in the early neonatal period and dysmature EEG patterns in the late neonatal period. They also showed maturation arrest in EEG patterns during prolonged mild depression of background EEG activities. In addition to strong sudden depression of CNS causing deep white matter injury and motor impairment, prolonged mild depression is another mode of brain injury in early preterm infants which can induce future cognitive impairment.

The case study of growth hormone in short-stature children offers an example of the high cost of bioengineered therapies and the attendant ethical concerns. Despite uncertainties as to its efficacy, it is estimated that the annual U.S. expenditure for growth hormone, which costs about $20,000 per year for a 30 kg child, exceeds $375 million dollars. Ultimately, at this point in its evolution, the use of GH therapy illustrates the dilemma commonly created by new medical technology--the chasm between what can be done and what should be done. Unfortunately, the knowledge of what can be done precedes the understanding of what should be done.

Background: Growth failure without organic aetiology but associated with behavioural disturbance and psychosocial stress has been termed psychosocial short stature. This condition is not a valid diagnostic entity, but encompasses failure to thrive, stunting secondary to chronic malnutrition, and idiopathic hypopituitarism. Some children show spontaneous catch-up growth when removed from the source of stress, without further treatment, but until now precise definition of this subgroup for the purpose of clinical identification has not been possible., Methods: Hospital-referred children with growth failure unrelated to organic pathology, who came from stressful homes, were compared with children of short-normal stature identified from an epidemiological survey (n = 31). Growth-hormone dynamics were studied in the hospital group by a combination of diurnal profiles and provocation tests. The tests were repeated after a hospital stay of 3 weeks away from familial stress. Standard behavioural measures were obtained from home and school., Findings: In a distinctive subgroup (n = 29), growth-hormone insufficiency was associated with characteristic behavioural features, especially hyperphagia and polydipsia, and a normal body-mass index. When the children were removed from their stressful home circumstances, growth-hormone insufficiency spontaneously resolved only in formerly hyperphagic subjects. 74% of the non-hyperphagic cases (n = 23) were anorexic, with a low body-mass index and normal growth-hormone responses to provocation tests., Interpretation: We present explicit behavioural and developmental criteria by which the novel syndrome of hyperphagic short stature may be recognised clinically. Such children have a capacity for spontaneous recovery of growth-hormone production on removal from or reduction of stress. Discriminant and predictive validity of the core symptoms are demonstrated. Preliminary familial studies indicate a possible genetic predisposition.

This study provides a controlled assessment of the psychological (and physical) effects of growth hormone treatment. Fifteen short 'normal' children (height SD score < -2) have been treated with growth hormone since the age of 7/8 years. They, together with untreated short controls and average controls (10th-90th centiles), were assessed at recruitment, after three years, and after five years. Only the treated group showed a significant height increase (SD score -2.44 to -1.21 over five years). No significant differences were found at recruitment, three years, or five years in IQ, attainment, behaviour, or self esteem. Also at five years, there were no significant differences in locus of control, self perception, or parental perceptions of competence. Both short groups displayed less satisfaction with their height than the controls (p < 0.01), though all groups were optimistic of being tall adults. The treated children were no more unrealistic over final height than the untreated children. To date, no psychological benefits of treatment have been demonstrated; but nor have there been any discernible ill effects for either the treated or the untreated children.

Short children are often described as having psychosocial problems. These reports may be inaccurate as former studies have relied largely on parental report. Psychosocial functioning of short children was assessed with the aim of using them and their peers as informants. Twenty two short (mean (SD) height -2.53 (0.28) SD score) prepubertal children aged between 6 and 11 years were recruited from growth clinics. Comparison children were recruited from each case child's class at school. Cognitive and psychosocial functioning was assessed. Peer relationships were measured using sociometry. There were no significant group differences in terms of peer acceptance, self perception, and social competence. Although cases described themselves as receiving less social support from teachers, no differences were evident in other areas of social support. Little evidence was found to suggest clinic referred prepubertal short children are psychosocially maladjusted. Further analysis revealed cognitive ability was a better predictor than height for most aspects of behavioural and emotional adjustment.