Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?

Saartje Straetemans,Jean De Schepper,Raoul Rooman

doi:10.3389/fendo.2021.678094

Abstract

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS <−2.0, or (2) nAH SDS minus mid-parental height SDS <−1.3, or (3) total ΔHt SDS <1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS <1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS <1.0 had an AUC >70%. First-year ΔHt SDS <0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

Highlights

The goal of growth hormone (GH) treatment in a GH deficient (GHD) child is to attain a true catch-up growth, resulting in an adult height (AH) close to target height [1]
The first-year growth response is most often used to evaluate the individual response to GH treatment [4, 5], allowing the early identification of GHD patients who may not respond to a physiological GH replacement and/or are not GHD
The first year response to GH, in general represented as DHt SDS, is used by many clinicians to identify those children who may or may not benefit from long-term GH treatment

Summary

Introduction

The goal of growth hormone (GH) treatment in a GH deficient (GHD) child is to attain a true catch-up growth, resulting in an adult height (AH) close to target height [1]. The pattern of GH induced growth consists of a first phase of accelerated growth, which allows the child to approach its target height in a number of years and is followed by a phase of maintenance growth where height velocity (HV) is normal. Several studies have evidenced that this GH induced growth acceleration diminishes rapidly, which is called the waning effect [2, 3]. This waning has been explained by a GH receptor desensitization, but its determinants have been poorly studied in children with GHD. We recently showed that the currently used first-year growth response and responsiveness parameters have a low sensitivity and/or specificity to predict a suboptimal adult height outcome after long-term GH treatment in prepubertal GHD children [6]

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Conclusion