Criteria for First-Year Growth Response to Growth Hormone Treatment in Prepubertal Children With Growth Hormone Deficiency: Do They Predict Poor Adult Height Outcome?

Saartje Straetemans,Jean De Schepper,Sylvie Tenoutasse,Raoul Rooman,Véronique Beauloye,Muriel Thomas

doi:10.3389/fendo.2019.00792

Abstract

Objective: Several criteria for first-year growth response (FYGR) to growth hormone (GH) treatment have been proposed. We explored which FYGR criteria predicted best the final height outcome after GH treatment in prepubertal children with GH deficiency (GHD).Design and methods: Height data of 129 GHD children (83 boys) who attained adult height and had been treated with GH for at least 4 consecutive years with at least 1 year before pubertal onset, were retrieved from the Belgian GH Registry. The FYGR parameters were: (1) increase in height (ΔHt) SDS, (2) height velocity (HV) SDS, (3) ΔHV (cm/year), (4) index of responsiveness (IoR) in KIGS prediction models, (5) first-year HV SDS based on the KIGS expected HV curve (HV KIGS SDS), (6) near final adult height (nFAH) prediction after first-year GH treatment. Poor final height outcome (PFHO) criteria were: (1) total ΔHt SDS <1.0, (2) nFAH SDS <−2.0, (3) nFAH minus midparental height SDS <−1.3. ROC curve analyses were performed to define the optimal cut-off for FYGR parameters to predict PFHO. Only ROC curves with an area under the curve (AUC) of more than 70% were further analyzed.Results: Twelve, 22 and 10% of the children had respectively a total ΔHt SDS <1, nFAH SDS <−2, and nFAH minus midparental height SDS <−1.3. The AUC's ranged between 73 and 85%. The highest AUC was found for first-year ΔHt SDS to predict total ΔHt SDS <1, and predicted nFAH SDS to predict nFAH SDS <−2. The currently used FYGR criteria had low specificities and sensitivities to detect PFHO. To obtain a 95% specificity, the cut-off value (and sensitivity) of FYGR parameters were: ΔHt SDS <0.35 (40%), HV SDS <−0.85 (43%), ΔHV <1.3 cm/year (36%), IoR <−1.57 (17%), HV KIGS SDS <−0.83 (40%) to predict total ΔHt SDS <1; predicted nFAH SDS (with GH peak) <−1.94 (25%), predicted nFAH SDS (without GH peak) <−2.02 (25%) to predict nFAH SDS <−2. At these cut-offs, the amount of correctly diagnosed poor final responders equals the amount of false positives.Conclusion: First-year growth response criteria perform poorly as predictors of poor final height outcome after long-term GH treatment in prepubertal GHD children.

Highlights

Growth hormone deficiency (GHD) in children is mostly idiopathic and is treated with daily growth hormone (GH) injections for a mean duration of 4 to 11 years [1,2,3,4,5,6,7,8]
The auxological data and GH treatment characteristics of prepubertal children diagnosed with GHD, who were enrolled in the Registry of the BElgian Society for PEdiatric Endocrinology and Diabetology (BESPEED) since 1986, were retrieved
Variables retrieved from the registry were (a) status at birth: sex, birth weight and length; (b) father’s and mother’s height (Ht); (c) pre-treatment Ht when measured between 6 and 18 months before GH treatment; (d) patient variables at the start of the treatment period: chronological age, Ht, weight (Wt), body mass index (BMI), the highest peak GH concentration during a provocation test, the presence of other pituitary hormone deficiencies, and (e) treatment modality: average GH dose during the first year of GH treatment

Summary

Introduction

Growth hormone deficiency (GHD) in children is mostly idiopathic and is treated with daily growth hormone (GH) injections for a mean duration of 4 to 11 years [1,2,3,4,5,6,7,8]. It is common practice to evaluate the response to GH therapy after 1 year to detect poor responders in order to reassess the diagnosis, adapt the GH dose or stop the treatment to avoid unnecessary daily injections and expenses. Models have been proposed that predict the near final height outcome after the first treatment year [16]. All these methods for evaluation of first-year growth response use arbitrary decision values that are not based on their ability to predict a final height outcome. The value of these first-year growth response and responsiveness parameters as predictors of a poor final height outcome after long-term GH treatment in GHD patients has not been analyzed.

Methods

Results

Conclusion