Towards Optimal Treatment with Growth Hormone in Short Children and Adolescents: Evidence and Theses

Abstract

Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Thus, a discussion of the factors relevant for achieving an optimal individual outcome in terms of growth, costs, and risks is required. In the present review, the heterogenous approaches of treatment with GH are discussed, considering the parameters available for an evaluation of the short- and long-term outcomes at different stages of treatment. This discourse introduces the potential of the newly emerging prediction algorithms in comparison to other more conventional approaches for the planning and evaluation of the response to GH. In rare disorders such as those with short stature, treatment decisions cannot easily be deduced from personal experience. An interactive approach utilizing the derived experience from large cohorts for the evaluation of the individual patient and the required decision-making may facilitate the use of GH. Such an approach should also lead to avoiding unnecessary long-term treatment in unresponsive individuals.

Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion

“…In summary, we confirm results from the only previous randomized study using high GH doses [24]. The widespread assumption, based on observational nonrandomized studies [27,30], that pubertal height gain cannot be improved by increasing GH dose during puberty, is not supported by the present randomized study in our large cohort.…”

“…Thus, the GH dose needs to be increased substantially in order to obtain a group-wide GH dose-dependent growth response in accordance with the broad variability in the growth response, reflecting the variation of responsiveness in whatever diagnostic groups. The available model for predicting individual pubertal growth in response to GH treatment includes only doses up to 42 µg/kg/day, which may confuse interpretation of the influence of dose on growth [26,30]. To address this, a model that includes a broader dose range needs to be developed, making individualized GH treatment during puberty possible, as it is in prepubertal children [31].…”

Individualised growth response optimisation (iGRO) tool: an accessible and easy-to-use growth prediction system to enable treatment optimisation for children treated with growth hormone

“…a Also applicable for SGA indication; fourth through eighth years. Adapted from Ranke et al [6], with permission of The Endocrine Society. …”

“…However, each child responds to a dose of rhGH in a unique way due to their genetic, metabolic and physical characteristics. Whilst many children with a given diagnosis respond as expected to rhGH treatment and are likely to reach the goals of intended treatment [5], some children respond less well [6] and some may respond better than expected [7].…”

Pharmacogenomics Related to Growth Disorders

“…1). Despite the wide spectrum of aetiology, treatment of these disorders, whether associated with growth hormone deficiency (GHD) or not, involves the use of recombinant human growth hormone (rhGH) [4,5]. Although recombinant human insulin-like growth factor (rhIGF-1) is available for the treatment of GH insensitivity syndromes, its wider role in the treatment of other growth disorders remains to be investigated [6].…”