Long‐term results of growth hormone therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues

Abstract

Summary BACKGROUND AND OBJECTIVE Growth hormone treatment In children with Idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long‐term effect of GH therapy in children with Idiopathic short stature. DESIGN We have treated 27 prepubertal children with ISS with recombinant human GH (rhGH) in an initial dosage of 2 IU/m2 body surface/day subcutaneously, which was doubled either after the first year if the height velocity increment was less than 2 cm/year, or thereafter if height velocity fell below the P50 for bone age. Growth and bone maturation of the treatment group (ISS group, n= 21) were compared to those of an untreated control group with ISS (ISS controls, n= 27) and of a group of rhGH treated children with isolated GH deficiency (GHD group, n= 7). RESULTS In 9 patients of the ISS group still on treatment, height standard deviation score (HSDS) for chronological age increased from −3.8±0.7 to −2.3±0.9 (mean±standard deviation) over 6 years, while in matched ISS controls HSDS for age did not change. HSDS for age in the GHD group increased from −3.9±0.6 to −1.8±0.7 after 4 years, significantly more than the ISS group. Bone maturation was accelerated In the ISS and GHD groups. HSDS for bone age and predicted adult height did not change in either group. Final height in 12 children of the ISS group was −2.6±1.0 SDS. In the untreated controls final height was similar. A low integrated GH concentration over 24 hours, a low GH peak to provocative stimuli, and minimal initial BA delay predicted a favourable outcome. CONCLUSION rhGH treatment In this group of children with Idiopathic short stature did not increase average final height. Part of the heterogeneity of the response can be attributed to the variation in endogenous GH secretion and initial bone age delay.

Age at Growth Hormone Therapy Start and First-Year Responsiveness to Growth Hormone Are Major Determinants of Height Outcome in Idiopathic Short Stature

“…up to 3 years) treatment with GH can increase height velocity in children with ISS [4,5,6]. There are also a number of reports dealing with treatment up to adult height [7,8,9,10,11,12, 14, 16, 17, 44,46,47,48,49], some of which involved children who were predominantly pre-pubertal when GH treatment started and in which untreated children were used as controls [8, 10, 14, 17,47,48,49]. Only one of these, however, was a randomized, double-blind, placebo-controlled study [17].…”

GH dependence and GH withdrawal syndrome in GH treatment of short normal children: evidence from growth and cardiac output

“…During 1-4 years of GH therapy, short children increase their growth rate and height standard deviation score (SDS) similar to the response seen in classical GH deficiency (GHD) (1)(2)(3)(4). The long term results are variable, with reports of no increase in the final height (5,6), a small increase (7), or a marked increase (8,9). As the collaborative Israeli study of efficacy and safety of GH therapy was analyzed (10), we realized that in 65 boys with GHD or neurosecretory dysfunction, aged 3-15 years, treated with 3 times weekly 0.1 mg/kg s.c. GH, the child's age was the most significant determinant of therapy outcome; boys of the prepubertal age group gained over the course of 3 years an average 8 cm of predicted adult height, pubertal boys over the age of 12 years showed a negative correlation of their predicted height gain against age, and boys over the age of 14 years showed a loss of predicted height during GH therapy.…”

Validated Multivariate Models Predicting the Growth Response to GH Treatment in Individual Short Children with a Broad Range in GH Secretion Capacities

“…Among children forming the continuum between these two extremes, diagnosis is more challenging; that is, children with partial GHD or those considered to have partial GHI, who may be classified as idiopathic short stature (ISS). Despite investigations and discussions aimed at attaining consensus on the diagnostic discrimination between GHD and ISS (1,2), none of the clinical measures used to date provide a reliable means for categorizing these patients and for predicting the value of GH therapy (3). The effect of the GH axis on statural growth in an individual child depends on the interaction between GH secretion and GH responsiveness.…”