Catch-down Growth Research Articles

Long Term Experience with Growth Hormone Treatment in Children with Chronic Renal Failure

After a decade of experience with recombinant human growth hormone (rhGH) in children with chronic renal failure (CRF), the long-term efficacy and safety of the drug is now established. In prepubertal children, partial catch-up growth is achieved during the first three treatment years, followed by sustained percentile-parallel growth. Discontinuation of rhGH treatment results in catch-down growth in 75% of patients. Treatment efficacy is inversely correlated with age and baseline height velocity, and positively influenced by genetic target height and residual renal function. Skeletal maturation is not accelerated, suggesting a true increase in final height potential. Side effects are limited to a stimulation of insulin secretion, which is not associated with changes in glucose tolerance, and occasional cases of benign intracranial hypertension. In summary, the advent of rhGH has opened a new era in the management of growth failure in CRF. Available evidence suggests that treatment should start in early childhood and early in the course of renal failure, and should be continued at least until renal transplantation. It remains to be seen whether the beneficial effect of rhGH on height observed during the prepubertal period will result in an eventual increase in adult height.

Treatment with GHRH(1‐29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity

Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1-29)NH2 (GHRHa) for a period of 12 months. Eighteen short pre-pubertal children (aged 4.3-11.0 years, 17 male) with idiopathic short stature (height < 3rd centile, peak GH to provocative testing > 20 mU/l) were recruited to receive GHRHa 20 micrograms/kg by twice daily s.c. injection for one year. One patient was non-compliant and was withdrawn prior to 3 months of therapy. Pretreatment height velocity was calculated for 12 months and subjects were measured 3-monthly during therapy. Overnight GH profiles and s.c. GHRH tests (20 micrograms/kg) were performed at 0, 3, 6 and 12 months of therapy. In addition, an i.v. GHRH test (1 microgram/kg) was performed at the start and after 1 month of therapy. Overnight GH profiles were analysed using the Pulsar program. Mean (SD) height velocity (HV) increased from 4.8(0.9)cm/year pre-treatment to 7.2(1.6)cm/year after 12 months of therapy (P = 0.001). The children growing slowly (HV < 25th centile) before treatment had a greater growth response than those growing normally (HV > or = 25th centile) before treatment. Final height prediction increased by a mean (SD) of 3.4(2.6)cm. Overnight GH levels and GH responses to GHRH testing fell during the 12 months of therapy. Fasting blood glucose and insulin levels increased during therapy, as did IGF-I. Cessation of GHRHa was followed by catch-down growth during the first 3 months off therapy: mean (SD) HV 3.89(1.82)cm/year (P < 0.04), although the HV after 6 months (4.9(1.0))cm/year) and 12 months (4.4(1.0)cm/year) was not different from pretreatment values. Short-term therapy with twice-daily s.c. injection of GHRHa (20 micrograms/kg) promoted linear growth in short children who were not GH-insufficient. The improved height velocity was sustained throughout the 12 months of treatment, followed by catch-down growth, and returned to pretreatment velocity after cessation of therapy.

Growth Hormone (GH) Treatment in Short Normal Children: Absence of Influence of Time of Injection and Resistance to GH Autofeedback*

Forty prepubertal subjects (25 boys and 15 girls) with idiopathic short stature, aged 3.8-14.6 yr, were randomly allocated to receive sc injections of recombinant human GH (hGH) 6 days/week at a dose of 3 IU (1.25 mg)/m2.day either in the morning or in the evening. After 6 months of therapy, each subject was switched over to the other schedule of injection. After 12 months, treatment was stopped, and the subjects were followed for 6 months. For the whole group, regardless of the time of injection, height velocity (centimeters per yr) was 4.3 +/- 0.9 before hGH treatment, 8.3 +/- 1.9 during the first 6 months of treatment, and 6.9 +/- 1.6 during the last 6 months of treatment. Thirty-three of 38 subjects (87%) who completed 12 months of therapy presented an increase in height velocity greater than 2 cm/yr. Two patients (5%) developed antibodies to hGH and were among the nonresponders. There was no significant difference in growth response according to the schedule of injections. GH-releasing hormone (GHRH) testing was performed before and after 6 and 12 months of hGH therapy. When the last hGH injection was performed 12 h before the GHRH test, there was a 36% decrease in the maximum GH response (P less than 0.01) and a 33% decrease (P less than 0.01) in the GH secretory area compared to those before therapy. When the last hGH injection was performed 24 h or more before the GHRH test, no significant differences were observed. Insulin-like growth factor-I levels were not significantly different when measured 12 or 24 h after hGH. During the 6 months after discontinuation of hGH therapy, catch-down growth was observed in 44% of the subjects. We conclude that the schedule of injection does not influence the growth response, which wanes after 6 months; this waning effect is not related to declining insulin-like growth factor-I levels or GH autofeedback, suggesting a peripheral mechanism. Likewise, the catch-down phenomenon after hGH is discontinued is not related to a persistent diminution of pituitary responsiveness to GHRH.

ONE YEAR EXPERIENCE WITH BIOSYNTHETIC HOMOLOGOUS HUMAN GROWTH HORMONE IN 81 CHILDREN WITH GROWTH HORMONE DEFICIENCY

Biosynthetic homologous human growth hormone (recombinant DNA) produced by Eli Lilly was given to 81 children treated for growth hormone deficiency (GHD) in 26 centers. Growth improved in all of them: 25 newly diagnosed patients increased their growth rate from 3.6 ± 1.7 to 11.9 +± 2.0 cm/y. 14 patients transferred from pituitary to biosynthetic hGH continued to grow with a velocity of 5.7 ± 2.2 cm/y compared to 5.0 ± 3.3 cm/y when given pit.-hGH. 42 patients with GHD receiving biosynth. hGH after an interruption of therapy for approx. one year grew with a velocity of 8.1 ± 2.0 cm/y on biosynth. hGH after a catch-down growth of 1.9 cm/y from a pit.-hGH induced growth rate of 7.2 ± 2.1 cm/y. The loss of growth during the interruption was not compensated for by catch-up growth. Therefore, any interruption of therapy may worsen the height prognosis. No side effects were observed and no specific antibodies against biosynth. hGH developed during therapy. Antibody-titers against E-Coli peptides remained unchanged during therapy.

Compensatory maturational deceleration of growth or "catch-down growth" in patients with congenital adrenal hyperplasia after delayed initiation of therapy.

The growth pattern is reported of 16 patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in whom therapy was started after the age of 3 years. Treatment was initiated at a mean chronological age (CA) of 4.7 years (range 3.0-7.2) and at a mean bone age (BA) of 10.4 years (range 10.2-13.2). It consisted of hydrocortisone (mean dosage 26 mg/m2) or prednisone (8.7 mg/m2) in all, and of fluorohydrocortisone (0.05-0.1 mg daily) in five patients. At the last examination the mean duration of therapy was 5.2 years, the mean CA 10.0 years, and the mean BA 12.6 years. In 13 of the 16 patients a "catch-down growth" pattern was observed, which was characterised by a decrease in height (expressed as SDS) for CA, a deceleration of bone maturation and increase of height (SDS) for BA, and an improvement in predicted height (Bayley-Pinneau).