Efficacy of Growth Hormone Replacement Therapy in Children with Organic Growth Hormone Deficiency after Cranial Irradiation

Abstract

We evaluated the growth response of 20 childhood cancer survivors who received growth hormone (GH) replacement therapy (0.3 mg/kg/week) for at least 12 months. In all subjects, GH deficiency was associated with cranial irradiation and was documented with growth charts, bone age, and somatomedin C levels; at least one GH stimulation test was available for 14 children. Pretreatment overall growth velocity was 3.3 ± 0.5 cm/year (mean ± SE)over a 3-year period. After GH replacement, growth velocity was 8.6 ± 0.6 cm/year during the first year (n = 20), 7.2 ± 0.5 cm/year during the second year (n = 17), 5.9 ± 0.6 cm/year during the third year (n = 11), and 6.1 ± 0.6 cm/year during the fourth year (n = 7). Growth response, tabulated by age at onset of GH replacement, was compared with the response in GH-naive children with idiopathic GH deficiency (data obtained through the Genentech Inc. National Cooperative Growth Study Summary, September 1991); the growth velocity fell within the range described for idiopathic GH deficiency adjusted for either chronological or bone age. We conclude that children with GH deficiency after cranial irradiation for neoplastic diseases respond to GH replacement therapy as well as children with idiopathic GH deficiency.

Growth Failure After Treatment of Pediatric Brain Tumors

“…Others have reported an increased time interval from brain tumor diagnosis to initiation of GH therapy averaging 4 to 5 years. 24,25 Although GH therapy does not appear to affect the late relapse rate of brain tumors, it seems reasonable to delay initiating GH therapy until 2 years after completion of brain tumor therapy because the contribution of exogenous GH to relapse would be difficult to interpret. 26,27 One patient with a medulloblastoma in our study recurred during this 2-year period.…”

Management and Surveillance of Short- and Long-Term Sequelae of Radiation Therapy for the Treatment of Pediatric Brain Tumors

“…Radiation dose > 27 Gy to the hypothalamic-pituitary-axis has been known to result in endocrinopathy including growth hormone (GH) deficiency, short stature, and early puberty with decreased duration of pubertal development. [47][48][49][50] GH and primary hypothyroidism are the most common deficiencies and can present 1 to 2 years post-RT, requiring longitudinal endocrine follow-up and surveillance well into adulthood with early initiation of GH therapy to prevent short stature. 51 Average time to starting GH therapy ranges from 2.5 to 5 years post-RT and should be delayed until 2 years after brain tumor treatment to negate possible effects of GH on tumor relapse.…”

The Endocrine Effects of Nonhormonal Antineoplastic Therapy

“…With intermediate and higher doses, GH response to arginine is impaired, and the frequency and amplitude of pulsatile GH secretion is decreased (328,329). At doses greater than 30 Gy, abnormal GH secretion and growth retardation are observed in more than 35% of patients (227), necessitating GH treatment (330).…”

“…GH replacement therapy in children with documented GH deficiency is effective and has been reviewed (330,423). Pediatric screening 1.…”