Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement.

Abstract

Final height (FH) outcome is important in survivors of childhood brain tumors. GH replacement is indicated in those found to be GH deficient (GHD). More recently, GnRH analogs (GnRHa) have been introduced to delay early or rapidly progressing puberty to allow more time for linear growth. Studies to FH are important to determine the effectiveness of growth-promoting strategies. Our aim was to assess whether evolving endocrine strategies have improved FH outcome and to determine whether GnRHa therapy has contributed auxologically. FH data were examined in 58 children (31 males and 27 females) with radiation-induced GHD who had been treated with GH. All had received a combination of cranial (CI; n = 17) or craniospinal (CSI; n = 41) irradiation with or without chemotherapy for a brain tumor. Eleven patients received GnRHa therapy. Throughout the 25 yr of the study patients came closer to achieving target height (i.e. a reduction in height loss), both those receiving CI (r = 0.5; P = 0.03) and those receiving CSI (r = 0.6; P < 0.001). The patients receiving GH therapy before 1988 compared with from 1988 onward had a similar age at irradiation [mean (+/-SD), 5.8 (3.0) vs. 6.2 (2.9) yr; P = 0.6], but experienced a more prolonged time interval from completing irradiation to starting GH [5.4 (2.4) vs. 3.3 (1.6) yr; P < 0.001]. Forward stepwise regression analysis revealed that height loss is affected by age at irradiation (P < 0.001), previous spinal irradiation (P = 0.02), chemotherapy (P < 0.001), and exposure to GnRHa therapy (P < 0.001). In the 11 patients treated with GnRHa therapy FH SD scores were improved compared with FH predictions calculated from a model derived from the patients not treated with GnRHa [-0.8 (1.6) vs. -2.4 (0.8) SD score; P < 0.001]. We have demonstrated an overall improvement in FH in children treated with GH for GHD after therapy for brain tumors over the last 25 yr. In the subset of children in whom the growth prognosis was adversely affected by early puberty, the combination of GnRHa and GH improved their prospects of achieving target height. The improved auxological outcome may reflect 1) the use of more standardized GH schedules and better dosing regimens, 2) a reduction in the time interval between finishing radiotherapy and receiving GH replacement, and 3) the use of GnRHa in addition to GH replacement in carefully selected patients.