Observed and Predicted Total Pubertal Growth during Treatment with Growth Hormone in Adolescents with Idiopathic Growth Hormone Deficiency, Turner Syndrome, Short Stature, Born Small for Gestational Age and Idiopathic Short Stature: KIGS Analysis and Review

Abstract

Background/Aims: The aim was to describe the factors determining total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD), Turner syndrome (TS), who were small for gestational age (SGA) or had idiopathic short stature (ISS). Methods: The patients were documented within KIGS (Pfizer International Growth Database). TPG was defined as growth from puberty onset – spontaneous (>B1 or testes >3 ml) or induced with sex steroids to adult height in idiopathic GHD (n = 639; males 399), TS (n = 463), SGA (n = 59; males 35), and ISS (n = 130; males 87). Algorithms to predict TPG at puberty onset were developed by multiple linear regression analysis. Results: In GHD (males, females) and TS TPG could be explained with the same four predictors: (1) age (years) at puberty onset (neg.), (2) age – bone age at puberty onset (pos.), (3) height – midparental height (SDS) at puberty onset (neg.), and (4) mean dose of growth hormone (GH) during puberty (pos.). The algorithms explained 66, 65 and 68%, respectively, of the variability with total errors of 4.5, 3.8 and 2.9 cm, in spontaneous and induced TPG. Conclusions: TPG is determined by the same factors at puberty onset in adolescents with GHD, TS, SGA or ISS treated with GH. Thus, TPG depends mostly on the outcomes achieved at the end of prepubertal growth and less so on the dose of GH.

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

“…The validated and published GPMs derived from KIGS [15][16][17][18][19] for GHD, TS and SGA indications were incorporated, as were specific disease and country reference charts for height, height velocity (HV) and weight. The tool was designed to offer flexibility to enable physicians to select and preset the appropriate reference tables for the three available indications.…”

“…However, such differences clearly reflect the current clinical setting in paediatric endocrinology. Yet, it is important to note that there is high concordance between the KIGS cohorts used to develop the prediction models and cohorts from other similar pharmaco-epidemiological surveys and case-control studies [15][16][17][18][19][21][22][23].…”

“…Mathematical analyses of large patient cohorts have shown that the magnitude of HV during GH treatment is a function of a multitude of factors such as the diagnosis, age, height, weight, the dose of GH given and other factors. Based on large cohorts of children with various growth disorders, such as GHD, TS and SGA, documented within KIGS, mathematical algorithms to predict the individual response to rhGH therapy have been derived and validated [15][16][17][18][19]. These algorithms (i.e.…”

“…Over the past decades, a number of GPMs for short children treated with rhGH for various diagnoses have been published [11,[13][14][15][16][17][18][19][20]. Most of these models require specific information not always available to the physician at the moment of the consultation.…”

TRANSITION IN ENDOCRINOLOGY: Treatment of Turner's syndrome during transition

“…During the last decade many studies showed growth hormone (GH) treatment as safe and effective for growth promotion in TS. Table 2 presents the results of growth therapy and indicates positive, negative and neutral determinants of therapy effectiveness as well as consequences and side effects of hormonal therapy in the analysed articles (4,5,7,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50).…”