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.

The evaluation and followup of children referred to pediatric endocrinologists for short stature.

Objective. To characterize the pediatric endocrinologists' evaluation and followup of short-statured patients. Study Design. Observational study of 21,548 short-statured children (April 1996 to December 1999). Baseline demographics, laboratory testing, height standard deviation score (SDS), target height, and height relative to target height were analyzed at initial and return visits with the specialist. Patients were scheduled for at least one return visit and no recombinant human growth hormone therapy was administered. Results. Mean patient age was 8.6 years with a mean height SDS of -2.1. Patients were predominantly male (69%), prepubertal (73%), and white (76%). Few screening tests were obtained during initial evaluation. Nearly 40% of children did not return for their second scheduled visit. The follow-up rate was unrelated to demographics or degree of short stature. Conclusions. Low return rates limit specialists' ability to monitor growth or obtain laboratory testing over time. Further studies are needed to determine which tests should be obtained at the initial clinic visit as well as the basis for the low return rate in this group of children.

First-year response to rhGH therapy in children with CKD: a National Cooperative Growth Study Report.

A clear definition of the appropriate growth response during recombinant human growth hormone (rhGH) treatment has never been established in the pediatric chronic kidney disease (CKD) population. We present here data from Genentech's National Cooperative Growth Study (NCGS) on the first-year growth response in prepubertal children with CKD. Using NCGS data, we constructed response curves for the first year of rhGH therapy in 270 (186 males, 84 females) naïve-to-treatment, prepubertal children with CKD prior to transplant or dialysis. Data from both genders were combined because gender was not significantly related to height velocity (p = 0.51). Response to rhGH was expressed as height velocity (HV) in cm/year. Mean, mean + or - 1SD, and mean - 2SD for HV during the first year of rhGH treatment as well as pretreatment HV were plotted versus age. Age-specific HV plots for rhGH-treated children with CKD are presented. At all ages, the first-year mean HV was greater than the mean pretreatment HV. The mean - 2SD for HV in children on rhGH treatment was similar to the mean pretreatment HV. These growth plots will be useful to clinicians for assessing a patient's first-year growth response. We propose that a HV below the mean - 1SD is an inadequate response. These curves may help identify patients with a suboptimal growth response due to confounding medical factors and/or non-compliance.

A stepwise increase in recombinant human growth hormone dosing during puberty achieves improved pubertal growth: a National Cooperative Growth Study report.

UNLABELLED: The magnitude of the pubertal growth spurt contributes to adult height. Children treated with increased doses of recombinant human growth hormone (rhGH) during puberty have shown improved near adult height (NAH) outcomes that varied by treatment duration. METHODS: Males, in a single clinic, treated with a prepubertal dose of rhGH (0.3 mg/kg/wk) received 0.1 mg/kg/wk dose increases with successive Tanner stages up to 0.6 mg/kg/wk. Changes in height and height SDS from pubertal onset to NAH were assessed in patients attaining NAH after > or =3 years (n = 23) and > or =4 years (n = 16). Using ANCOVA, outcomes were compared to closely matched patients (n = 758) from the National Cooperative Growth Study treated with a fixed dose (0.3 mg/kg/wk) throughout puberty. RESULTS: Compared to matched patients, a 3.6 cm greater increase in mean height gain and a 0.49 greater increase in mean height SDS (p <0.0001) during puberty was observed in patients attaining NAH after > or =3 years. Corresponding values were 3.9 cm and 0.54 (p <0.0001) in patients attaining NAH after > or =4 years. CONCLUSION: Stepwise increases in rhGH improved pubertal height gain when compared to a fixed dose and may represent an alternate approach to managing the patient during puberty.

Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone.

CONTEXT: Noonan syndrome (NS) is a heterogeneous genetic disorder characterized by short stature. SETTING: The National Cooperative Growth Study (NCGS), a postmarketing observational study of recombinant human GH (rhGH)-treated children, includes a large cohort of children with NS. PATIENTS: We studied NCGS-enrolled prepubertal and pubertal children with NS. MAIN OUTCOMES: Baseline characteristics and growth responses in NS patients with reported near-adult height (NAH) (n = 65) were compared to patients with idiopathic GH deficiency (n = 3007) and Turner syndrome (TS; n = 1378) with reported NAH to identify factors contributing to NAH optimization in NS. RESULTS: NS patients (mean enrollment age, 11.6 yr) received rhGH (mean, 0.33 mg/kg . wk) for a mean of 5.6 yr. No significant difference was observed in Delta height sd score (SDS) between NS (+1.4 +/- 0.7) and TS (+1.2 +/- 0.9). However, Delta height SDS for NS and TS differed significantly from idiopathic GH deficiency (+1.7 +/- 1.0) (P < 0.0001). Mean gain in NAH above projected was 10.9 +/- 4.9 cm (males) and 9.2 +/- 4.0 cm (females). Duration of prepubertal rhGH was an important contributor to prepubertal change in height SDS (r(2) = 0.97). Height SDS at pubertal onset highly correlated with NAH SDS (rho = 0.783; P < 0.0001). Duration of puberty highly correlated with pubertal height gain in centimeters for males (rho = 0.941) and females (rho = 0.882) (P < 0.01). No new adverse events were observed. CONCLUSIONS: rhGH significantly improved height SDS for children with NS at NAH. Duration of prepubertal rhGH and height SDS at puberty were important contributors to NAH. Because starting age of the patients in this report was 11.6 yr, these data suggest that greater growth optimization is possible with earlier initiation of therapy.