Septo-optic dysplasia/optic nerve hypoplasia: data from the National Cooperative Growth Study (NCGS)

We analyzed data from 65 children with septo-optic dysplasia (SOD) referred for evaluation and followed in the National Cooperative Growth Study (NCGS) Substudy 8 and from 758 children treated with growth hormone (GH) and followed in the NCGS core study. Compared to other children referred for evaluation of short stature, children with SOD were younger (mean age 3.7 +/- 3.6 vs 8.6 +/- 4.9 years), had less severe short stature (mean +/- SD height SDS -1.80 +/- 1.64 vs -2.17 +/- 0.95), and were more likely to be female (46% F vs 31% M). Children with SOD who received GH were older and shorter than those referred and untreated, but the gender distribution was similar. Other pituitary hormone deficits were reported in untreated patients, including thyroid hormone deficiencies (8%) and adrenocorticotropic hormone (ACTH) deficiency (3%), as compared to 27% and 24%, respectively, in GH-treated children. Data on adult height were available for 71 patients, who showed an average gain in height SDS of 1.17 +/- 1.49. GH therapy was well tolerated in children with SOD.     

Growth hormone responsiveness: peak stimulated growth hormone levels and other variables in idiopathic short stature (ISS): data from the National Cooperative Growth Study

HYPOTHESIS: In children with idiopathic short stature (ISS), growth hormone (GH) response to a provocative test will be inversely related to the first year response to hGH and be a variable accounting for a degree of responsiveness. BACKGROUND: Because high levels of GH are a characteristic of GH insensitivity, such as in Laron syndrome, it is possible that a high stimulated GH is associated with a lower first year height velocity among children diagnosed as having ISS. METHODS: We examined the relationship between the peak stimulated GH levels in 3 ISS groups; GH >10 -<25, 25-40, and >40 ng/mL and the first year growth response to rhGH therapy. We also looked at 8 other predictor variables (age, sex, height SDS, height age, body mass index (BMI), bone age, dose, and SDS deficit from target parental height. Multiple regression analysis with the first year height as the dependent variable and peak stimulated GH was the primary endpoint. The predictive value of adding each of the other variables was then assessed. RESULTS: Mean change in height velocity was similar among the three groups, with a maximum difference among the groups of 0.6 cm/yr. There was a small but statistically significant correlation (r=-0.12) between the stimulated GH and first year height velocity. CONCLUSIONS: The small correlation between first year growth response and peak GH is not clinically relevant in defining GH resistance. No cut off level by peak GH could be determined to enhance the usefulness of this measure to predict response. Baseline age was the only clinically significant predictor, R-squared, 6.4%. All other variables contributed less than an additional 2% to the R-squared.     

Characteristics of growth hormone therapy for pediatric patients with brain tumors in the National Cooperative Growth Study (NCGS) and from a survey of pediatric endocrinologists

Pediatric patients with brain tumors may have significant short stature secondary to growth hormone deficiency (GHD). This occurs as a result of impaired hypothalamic function due to tumor location, radiation therapy, surgery, or chemotherapy. The use of GH replacement therapy in this patient population is variable and somewhat unpredictable. We analyzed patient data from the National Co-operative Growth Study (NCGS) database and a survey completed by 19 members of the Pediatric Endocrine Alliance for Neuro Oncology Patients (PEANOP) to identify patterns of GH use in pediatric patients following treatment for brain tumors. From the NCGS database, we present demographic, dosing, and safety data. The PEANOP survey was examined to determine the percentage of patients receiving GH and the likelihood of treating these patients with GH following tumor treatment. The time to initiating GH replacement therapy was evaluated in 14 tumor types, as well as the contributing impact of the extent of tumor resection.     

Fetal magnetic resonance imaging: jumping from 1.5 to 3 tesla (preliminary experience)

Several attempts have been made at imaging the fetus at 3 T as part of the continuous search for increased image signal and better anatomical delineation of the developing fetus. Until very recently, imaging of the fetus at 3 T has been disappointing, with numerous artifacts impeding image analysis. Better magnets and coils and improved technology now allow imaging of the fetus at greater magnetic strength, some hurdles in the shape of imaging artifacts notwithstanding. In this paper we present the preliminary experience of evaluating the developing fetus at 3 T and discuss several artifacts encountered and techniques to decrease them, as well as safety concerns associated with scanning the fetus at higher magnetic strength.     

Growth hormone treatment of idiopathic short stature: analysis of the database from KIGS, the Kabi Pharmacia International Growth Study

Within the Kabi Pharmacia International Growth Study (KIGS) database, there is information on 1017 (700 male/317 female) patients with idiopathic short stature (ISS). These patients were started on recombinant human growth hormone (GH) at a median age of 10.8 years, a bone age of -1.8 SDS, a height of -2.6 SDS and a predicted adult height (PAH) (Bailey–Pinneau method) of -2.5 SDS. The median dose of GH was 0.6 IU/kg body weight/week and the frequency of injections was six/week. According to the relationship with target height the patients were classified into'familial short stature (FSS)'(height SDS > target height SDS - 1.28) and into'non-FSS'(height SDS < target height SDS - 1.28). During the first year of GH treatment there was an overall increment in the median height velocity from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross-sectional analysis demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive correlation between gain in PAH and the GH dose (n = 202, r = 0.18, p < 0.01) during the first year. Longitudinal analysis in 84 patients showed an overall increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS first-year prediction model for patients with idiopathic GH deficiency on cohorts of prepubertal children with FSS and non-FSS, a lower responsiveness to GH in the non-FSS group was observed. It is concluded that higher than substitutive doses of GH are required for the long-term improvement of growth in ISS.     

Intracranial hypertension in pediatric patients treated with recombinant human growth hormone: data from 25 years of the Genentech National Cooperative Growth Study

Intracranial hypertension (IH) is a rare condition in children. However, a relationship between recombinant human growth hormone (rhGH) therapy and IH has been well documented. Risk factors were assessed for 70 rhGH-naive patients enrolled in the National Cooperative Growth Study with reports of IH after treatment initiation. Patients with severe growth hormone deficiency, Turner syndrome, chronic renal insufficiency (CRI), and obesity (particularly in the CRI group) were at highest risk of developing IH during the first year of therapy, suggesting initiation of careful early monitoring. In some patients, factors such as corticosteroid use or other chromosomal abnormalities appear to confer a delayed risk of IH, and these patients should be monitored long-term for signs and symptoms of IH.     

Magnetic resonance imaging in spinocerebellar degenerative diseases (apropos of 8 cases)

The results of NMR imaging in 8 cases of spinocerebellar degenerative diseases (age 4 to 19 years) are presented. In Friedreich ataxia (5 cases), spinal atrophy was constant and often severe, and was associated with a moderate cerebellar and/or bulbar atrophy in 3 cases. In hereditary spastic paraplegia, the only finding was a mild spinal atrophy in 2 of the 3 cases.     

Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect

OBJECTIVES: To investigate in an open-label randomized study, the effect of two doses of growth hormone (GH) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature (mean baseline height standard deviation score [SDS] -3.2). STUDY DESIGN: Patients were treated with GH at 0.24 mg/kg/week, 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter (0.24-->0.37), or 0.37 mg/kg/week. Final height was evaluated in 50 patients at study completion (mean treatment duration, 6.5 years). RESULTS: Patients who received 0.37 mg/kg/week (n = 72) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week (n = 70) (treatment difference = 0.8 cm/year; P = .003) or 0.24-->0.37 mg/kg/week (n = 67) (treatment difference = 0.9 cm/year; P = .001). For the 50 patients for whom final height measurements were available, mean height SDS increased by 1.55, 1.52, and 1.85 SDS, respectively, for the three dose groups. For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, the mean treatment difference (adjusted for differences in baseline predicted height SDS) was 0.57 SDS (3.6 cm; P = .025). Mean overall height gains (final height minus baseline predicted height) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, respectively, without dose effects on safety parameters. Final height measurements were within the normal adult height range for 94% of patients randomized to 0.37 mg/kg/week who continued to final height. CONCLUSION: GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature.     

Short- and long-term (final height) data in children with normal variant short stature treated with growth hormone

Seventeen children with normal variant short stature and a predicted height below −2 SDS were treated with growth hormone (GH) six times a week for a period of 5 years. Patients were randomly selected to receive three different doses of GH, group 1 (n=6) 3␣IU/m² per day, group 2 (n=6) 4.5 IU/m² per day and group 3 (n=5) 3 IU/m² per day in the 1st year and 4.5␣IU/m² per day thereafter. There was a significant increase in height after 1 and 2 years for all patients and for all subgroups. However, this increase was not dependent on GH dose. The decrease in height velocity during the 2nd year was not prevented by the increase of GH dose in group 3. The change of predicted height after 2 years was +0.75 SDS (according to Tanner Whitehouse). Fourteen children have been treated for 4␣years and 8 children for 5 years without a further change in height prediction. Nine patients have reached final height which was 2.4 cm (+0.41 SDS) above pretreatment height prediction. Final height was nearly identical to predicted height after 1 year of therapy. Conclusion An increment in height prediction was observed during the first 2 years of GH treatment and maintained thereafter. However, there was only a minor increase in final height over predicted height which does not justify the general use of GH in children with normal variant short stature. Received: 19 December 1996 / Accepted: 21 February 1997     

Growth hormone secretion and long-term growth data in children with psychosocial short stature treated by different changes in environment

OBJECTIVES: We assessed auxological and endocrine data of 65 children (32 girls) from 51 families with an average age of 6.6 years (range, 0.9 to 16.5 years, all but five prepubertal) with psychosocial short stature. METHODS: Fifty-one patients had an assessment of growth hormone (GH) secretion. Thirty-four were subjected to repeated testing with the first test being performed when the child was still in the adverse environment and the next testing after the child was removed. Twenty-five out of those 34 were repeatedly tested during one uninterrupted hospital admission with limited parental access. Thirty patients had a definite, long-term change in their environment (13 were separated from their families) and were assessed concerning their auxological data. RESULTS: Of the 34 patients who had repeated endocrine testing, 11 (32%) showed reversible GH deficiency (GHD), nine (26%) increased their previously normal peak GH concentration, and six (18%) had apparently irreversible GHD. Patients who had a change in environment increased their mean height velocity SDS from -0.9 (SD 1.5) to +1.5 (2.3) (p < 0.0001). Accordingly, height SDS increased from -2.9 (SD 0.8) before to -2.6 (SD 0.8) after the change (p < 0.001). CONCLUSION: One of the diagnostic features of psychosocial short stature is reversible GH insufficiency, which usually normalises after the child is separated from the adverse environment. Catch-up growth is always found after a positive change in the environment, and may occur within the family. However, if a change in environment is not possible, GH therapy may be an option.     

Growth post renal-transplantation in children: lessons from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)

Growth retardation following successful transplantation has been noted since the availability of ESRD care for children more than a quarter of a century ago. During the past decade, data collection and analysis of the NAPRTCS data base have detailed the factors which have an impact on growth in renal allograft recipients transplanted in the cyclosporine era. These analyses have led to the following conclusions. 1. Standardized height (z score) worsens in the majority of pediatric recipients following renal transplantation. 2. Catch-up growth (improvement in standardized height) occurs primarily in recipients <6 years of age at transplantation. Therefore, age at transplantation is a significant factor determining the magnitude of post-transplant growth. 3. Reduced allograft function has a profound negative impact on growth following transplantation. 4. Height deficit at the time of transplantation correlates with increment in height following transplantation. The most profoundly growth-retarded recipients exhibit the greatest increase in standardized height. 5. Race has been identified by NAPRTCS as a factor affecting post-transplant growth. Caucasian recipients exhibit a greater improvement in standardized height compared to African-American and Hispanic recipients. 6. Since serial evaluation of NAPRTCS data indicates that catch-up growth is unlikely to occur in 75% of renal allograft recipients, strategies such as the use of growth hormone would be advantageous in the future.     

Understanding the seasonal pattern of childhood asthma: results from the National Cooperative Inner-City Asthma Study (NCICAS)

OBJECTIVE: To contrast the seasonal patterns of asthma symptoms and utilization and determine the impact of allergen sensitivity, environmental tobacco smoke (ETS) exposure, and air pollution on the seasonal patterns of asthma. STUDY DESIGN: Participants in the National Cooperative Inner-City Asthma Study (NCICAS) were tracked for approximately 4 years after allergen skin testing and determination of exposure to ETS. Air pollution data were obtained from EPA monitoring sites in NCICAS cities. RESULTS: Asthma symptoms (wheeze) and health care utilization (unscheduled visits and hospitalization) had similar seasonal patterns, with low points during the summer months of June through August and a distinct autumn peak beginning in September. Seasonal patterns were similar among children with no allergen skin test reactivity, those reactive only to indoor allergens, and those reactive to outdoor allergens. ETS exposure, whether defined by self-report or urinary cotinine/creatinine ratio, was not related to the observed seasonal patterns. Among the pollutants evaluated, only the seasonal pattern of SO(2) coincided with that of asthma morbidity. CONCLUSIONS: Atopy, ETS, and most air pollutants do not appear to contribute to the distinct asthma seasonal pattern. On a population level, changes in symptoms are mirrored by changes in utilization.     

Spinal dysraphism: use of magnetic resonance imaging in evaluation

Three cases of children with spinal dysraphism are reported. Magnetic resonance imaging (MRI) was used as a primary diagnostic examination. The ages of the patients were 2 days, 4 years, and 16 years. In all instances the scan gave a precise diagnosis as well as well as an accurate delineation of the structural abnormalities before surgical treatment. Plain radiographs and ultrasound analysis may not be helpful, and invasive procedures can be associated with morbidity. Technical ease, safety, and anatomic precision suggest that MRI should be performed as a primary radiologic examination in the diagnostic workup of spinal dysraphism.     

Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature

OBJECTIVE: To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. STUDY DESIGN: Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. RESULTS: Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). CONCLUSIONS: Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.