Growth Hormone Treatment and Health-related Quality of Life in Children and Adolescents

A National, Prospective, One-Year Controlled Study

Gary Butler; Tymoteusz Turlejski; Gillian Wales; Linda Bailey; Neil Wright

Disclosures

Clin Endocrinol. 2019;91(2):304-313. 

In This Article

Abstract and Introduction

Abstract

Background: Health-related quality of life (HRQOL) may improve as an additional benefit of the growth hormone treatment (GHT) in children with short stature, but this effect has not been conclusively proven.

Objectives: To explore the direct effect of GHT on HRQOL in children starting GHT due to isolated or multiple GH deficiency (IGHD), acquired GH deficiency (AGHD) and Turner syndrome (TS), in comparison with untreated short stature controls in 18 UK centres.

Methods: We used recognized measures of HRQOL, the PedsQL, the Strengths and Difficulties Questionnaire and Youth Life Optimism Test scales to investigate the effect of GHT at 0, 6 and 12 months in children and adolescents 6–16 years with IGHD (n = 73) and AGHD (n = 45), and 22 girls with TS. 49 children with non-GHD short stature served as the controls.

Results: Children rated their HRQOL better than their parents. Those with IGHD and TS rated their overall HRQOL lower than the controls at baseline, psychosocial scores significantly lower in IGHD. After 12 months, the control and TS groups scored higher than UK norms. Those with AGHD had lowest HRQOL scores at all time points, due to poorer physical functioning. The controls showed the greatest improvement in the strength and difficulties scale. All measures evaluated, whether from child, parent or teacher showed an equal improvement over the year of GHT with no discernible direct treatment effect, despite reduced numbers in some patient groups.

Conclusions: Children with short stature resulting from GHD have lower functioning than controls but HRQOL appears to improve with GHT, most likely on account of greater attention and as a result of the retest phenomenon. We were not able to demonstrate an absolute and independent effect of GHT in itself. HRQOL should not be used as a primary measure, as in adults, to determine whether children should receive GHT.

Introduction

Growth hormone treatment (GHT) is the recommended therapeutic strategy for improving growth in children with growth hormone deficiency (GHD) and short stature. GHT, it is suggested, might also improve psychological, social and cognitive well-being. Health-related quality of life (HRQOL) has been recognized as an important end-point in children with short stature undergoing GHT. The 2008 Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature (ISS) concluded: 'An important rationale for treatment with GH is the assumption that it will improve quality of life (…). Future studies on the management of children with ISS should involve (…) psychosocial instruments, interventions and outcomes'.[1]

The current literature does not provide a conclusive opinion whether short stature should be considered as a handicapping condition or whether GHT improves quality of life. Specifically, studies have reported lower social acceptance and functioning,[2,3] problems with attention,[4] reduced body satisfaction, self-esteem[5] a higher rate of depressive tendency.[6] However, others reported no significant differences in HRQOL between short stature and normal healthy children.[7–12]

The direct effect of GHT has been extensively evaluated in adult patients, and in the UK, a deficit of HRQOL and its subsequent improvement are requirements for the initiation and continuation of GHT.[13] There is little evidence to support any claim that GHT should be offered to children for its supposedly beneficial effect on HRQOL. HRQOL is a multidimensional construct, so any attempt at evaluation will inevitably have its limitations.

Older studies found no difference in parent reports of child HRQOL, proxy indicators of child HRQOL such as school attendance and educational achievement or general psychological adjustment HRQOL when comparing children undergoing GHT with untreated or short, healthy control groups.[3,7,10,11] Comprehensive, longitudinal studies using standardized and specific measures of self-reported HRQOL backed up by independent parent and teacher assessments however are lacking.

One study randomized 68 children with ISS to receive either GHT or placebo, but this latter arm was later dropped due to poor recruitment.[11] Similar findings of HRQOL markers (social adjustment, self-esteem) were shown at baseline, and the benefit of GH was restricted to a minor improvement in parents' perception of child behaviour, but no differences were observed by children in self-reported questionnaires on functioning.

Van Pareren et al reported an improvement in behaviour and cognitive abilities in a cohort of short, healthy children born small for gestational age which correlated with GH-induced increase in height.[14] Chaplin et al claimed an effect of GHT in short prepubertal children, but did not provide control group comparisons.[15] More recently, a cohort of Japanese GHD children found significant correlations between GH-induced growth in self-reported measure of HRQOL in[16] in line with earlier findings by Stabler et al,[17] but there was no correlation with parent-rated HRQOL scores and catch-up growth. Unfortunately, there was no age-matched control group, and the mean age and age distributions were significantly different between the GHD and ISS groups.

These conflicting findings may arise on account of a lack of consensus on which variables to use and how to measure them. A wide range of outcomes reported by children, parents and teachers have been studied, and the lack of age-matched and gender-matched controls has narrowed the scope of conclusions that can be drawn for clinical practice. Attempts at comparing children undergoing GHT with healthy children are also limited by the need for utilizing generic, rather than disease-specific measures of HRQOL. Moreover, none of the published studies thus far has provided analysis of population subgroups according to the indication for starting the GHT and its specific effects. Our study aims to address these issues and to examine as best as possible changes if any on HRQOL in order to clarify the scope of benefits of GHT if any and facilitate informed decision-making in clinical practice. There is also an inevitable risk of methodical bias in unblinded study designs, but we have striven to conduct a study to tease out treatment from measurement effects[18] and also highlight known parent-child reporting differences.[19]

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