ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2018 Aug 1; 103(8): 2794

This systematic review and meta-analysis was conducted by a US Endocrine Society Task Force in order to inform new guidelines on the management of childhood cancer survivors (CCS). The aim of this review was to evaluate the effects of GH therapy on final height, risk of diabetes mellitus, lipid abnormalities, metabolic syndrome, quality of life, secondary tumors, and disease recurrence among CCS with tumors/surgery in the hypothalamic-pituitary (HP) region and CCS subjected to cranial (CIR), or craniospinal (CSI), or total body (TBI) irradiation. Twenty-nine observational studies were included. Sixteen studies compared CCSs treated or untreated with GH. Thirteen studies compared CCSs treated with GH against matched healthy controls, or controls with idiopathic GHD or idiopathic short stature.

In CCS, GH therapy was associated with no increase in tumour relapse or secondary neoplasia occurrence, and with a height gain of +0.61 SDS [95% CI, 0.08 to 1.13]. The risks of diabetes, abnormal lipid profile, metabolic syndrome, and poor quality of life were not increased. One study showed that the risk of a second neoplasia in CCS treated with GH was lower after an extended follow-up (1). This risk became non-significant after adjusting for sex, age at primary diagnosis, CIR dose/time, and treatment type in a later report on the same cohort (2). The dose of GH and treatment modalities did not differ between patients with and without recurrence, and there was no association between risk of recurrence with the cumulative duration of GH therapy or the time elapsed since treatment start.

There have been no definitive studies on how long to wait after the completion of cancer therapy to start GH therapy. US Pediatric Endocrine Society guidelines suggest to wait for 12 months (3). The strengths of this review relate to the comprehensive literature search. However, the available evidence is all observational, with related limitations. Most studies assessing GH therapy had relatively short follow-up duration, which limits the assessment of long-term risks of recurrence and secondary neoplasia. Additional studies with a longer follow up are needed to better define these risks.

References: 1. Sklar CA, Mertens AC, Mitby P, Occhiogrosso G, Qin J, Heller G, Yasui Y, Robison LL. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2002; 87: 3136–3141.

2. Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M, Robison LL, Meacham LR. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the childhood cancer survivor study. J Clin Endocrinol Metab. 2014; 99: 2030–2037.

3. Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 2016; 86: 361–397.