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?

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.

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model

“…We propose a new prediction model for nFHt. Most models predict the short-term response to treatment [23,[32][33][34][35] or the total pubertal growth [31], but a few papers propose a statistical model to predict FHt or nFHt [17][18][19]. We obtained 2 different models through the polynomial regression: one that predicts nFHt and one that predicts nFHt SDS.…”

Karyotype Abnormalities in the X Chromosome Predict Response to the Growth Hormone Therapy in Turner Syndrome

“…This allows for a growth spurt; hence, none of the presented patients were treated with E–P therapy. Many authors believe the first 2 years of treatment to be an indicator of response to rhGH therapy [ 22 , 23 ].…”

“…It is well known that the first and second years of treatment are usually a catch-up period, and the subsequent years represent a period of stabilization of the effect. Due to the fact that, in girls with TS, in addition to rhGH, the growth-promoting effect depends on the initiation of E–P therapy, we used the prepubertal period for our analysis, and we closed it at the stage just before starting E–P therapy [ 22 , 23 ].…”

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

“…Unfortunately, the studies did not provide sufficient evidence on the advantage of any of the proposed criteria and-in general-have led to the conclusion that all the criteria based on first-year growth response "perform poorly as predictors of poor final height outcome" [70]. Unfortunately, extending the observation of growth response up to 2 years did not improve the prediction of poor adult height outcome after rhGH therapy [72].…”