Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement.
AuthorsGleeson, Helena K
Ogilvy-Stuart, Amanda L
Brennan, Bernadette M
Shalet, Stephen M
AffiliationDepartments of Endocrinology, Pediatric Oncology and Clinical Oncology, Christie Hospital, Manchester, United Kingdom M20 4BX.
MetadataShow full item record
AbstractFinal 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.
CitationImprovements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. 2003, 88 (8):3682-9 J. Clin. Endocrinol. Metab.
JournalThe Journal of Clinical Endocrinology and Metabolism
- The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study.
- Authors: Saggese G, Federico G, Barsanti S, Fiore L
- Issue date: 2001 May
- Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia.
- Authors: Quintos JB, Vogiatzi MG, Harbison MD, New MI
- Issue date: 2001 Apr
- Reassessment of growth hormone status is required at final height in children treated with growth hormone replacement after radiation therapy.
- Authors: Gleeson HK, Gattamaneni HR, Smethurst L, Brennan BM, Shalet SM
- Issue date: 2004 Feb
- Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone.
- Authors: Pasquino AM, Pucarelli I, Roggini M, Segni M
- Issue date: 2000 Feb
- High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group.
- Authors: Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J
- Issue date: 2000 Oct