Treatment Of Idiopathic Short Stature Research Articles

Efficacy and Safety Results of Longterm Growth Hormone Treatment of Idiopathic Short Stature

Efficacy and Safety Results of Longterm Growth Hormone Treatment of Idiopathic Short Stature

Efficacy and Safety Results of Long-Term Growth Hormone Treatment of Idiopathic Short Stature

Small clinical trials of GH treatment of idiopathic short stature (ISS) show variable efficacy. The study was an analysis of a large GH registry for efficacy and safety of GH treatment of ISS. There was also a comparison with a specific clinical trial. Up to 7 yr of GH treatment of ISS was evaluated for efficacy and safety in the National Cooperative Growth Study (NCGS). The NCGS study was conducted at Genentech, Inc. and included 47,226 patients. The ISS group included maximum stimulated GH 10 ng/ml or more and/or a report of ISS by investigator (n = 8018; all included for safety). Cohort 1 (n = 2520) was similar to the clinical trial, cohort 2 (n = 283) included subjects younger than 5 yr of age, and cohort 3 (n = 940) was pubertal at GH start. GH, approximately 0.30 mg/kg.wk, was given. These included growth velocities and height sd (HtSDS). Mean first-year growth velocities in cohorts 1, 2, and 3 increased 4.6, 3.9, and 4.4 cm/yr over pretreatment, respectively. Measures included: baseline mean HtSDS, -2.9, -3.2, and -2.8; mean HtSDS at 1 yr, -2.4, -2.3, and -2.3, respectively. Mean HtSDS after 7 yr in cohorts 1 (n = 303) and 2 (n = 85) and 5 yr in cohort 3 (n = 58) were: -1.2, -1.0, and -1.5, respectively. Cohort 3 shorter treatment time was due to advanced baseline age (mean 13.8 yr) and puberty. Mean HtSDS gain in cohort 1 was comparable with the clinical trial. No new safety signals specific to the NCGS ISS population were observed. ISS patients in the GH registry demonstrate a significant increase in HtSDS with the safety profile similar to GH-deficient patients. RESULTS were similar to the clinical trial.

Growth hormone treatment of idiopathic short stature: Clinical studies

The selection of short-statured children for growth hormone (GH) treatment has long been complicated by the requirement for provocative testing that is unphysiologic, difficult to administer, and potentially dangerous. The recent FDA approval of GH for the treatment of children with idiopathic short stature allows treatment decisions to be based more on the degree of short stature and the potential for attaining a normal adult height. Several studies conducted in children have shown that GH therapy can effectively and safely produce height outcomes within a normal adult range. The observed variability in height response associated with GH use in some of these studies has left the clinician with a difficult decision. Still, the availability of GH for this patient population provides a rational treatment option for patients who fail arbitrary and inaccurate assessments.

Growth hormone treatment of idiopathic short stature: History and demographic data from the NCGS

Idiopathic short stature (ISS) is a term used to describe children without an identifiable cause for growth failure; these children comprise the largest group of candidates for growth hormone (GH) therapy. Over the past four decades, clinical trials have examined the efficacy and safety of GH treatment in the ISS population; for many of these trials, interpretation of results has been limited by variability in the criteria for ISS, small numbers of subjects, and a short term of study. Recent trials involving larger GH doses for longer periods suggest greater height improvements, but extrapolation to the larger ISS population is still debated. The National Cooperative Growth Study (NCGS) provides an opportunity to evaluate the treatment trends over time. In 1994, there were 20,279 patients enrolled in the NCGS, and 25% were identified as ISS. The most recent analysis was in 2003, and at that time 47,226 patients were enrolled; but only 17% were identified as ISS. This most recent analysis of patients enrolled in the NCGS provides a framework for examining the impact of this new indication for GH on clinical practice patterns.

Safety of Growth Hormone Treatment in Pediatric Patients with Idiopathic Short Stature

Recombinant human GH was approved by the United States Food and Drug Administration in 2003 for the treatment of idiopathic short stature (ISS). However, to date, the safety of GH in this patient population has not been rigorously studied. The objective of this study was to address the safety of GH treatment in children with ISS compared with GH safety in patient populations for which GH has been approved previously: Turner syndrome (TS) and GH deficiency (GHD). The rates of serious adverse events (SAEs) and adverse events (AEs) of particular relevance to GH-treated populations were compared across the three patient populations among five multicenter GH registration studies. Children with ISS, TS, or GHD were studied. Treatment consisted of GH doses ranging from 0.18-0.37 mg/kg.wk. The main outcome measures were rates of SAEs and AEs of special relevance to patients receiving GH. Laboratory measures of carbohydrate metabolism were used as outcome measures for the ISS studies. Within the ISS studies, comprising one double-blind, placebo-controlled study and one open-label, dose-response study, SAEs (mainly hospitalizations for accidental injury or acute illness unrelated to GH exposure) were reported for 13-14% of GH-treated patients. Overall AE rates (serious and nonserious) as well as rates of potentially GH-related AEs were similar in the GHD, TS, and ISS studies (for ISS studies combined: otitis media, 8%; scoliosis, 3%; hypothyroidism, 0.7%; changes in carbohydrate metabolism, 0.7%; hypertension, 0.4%). Measures of carbohydrate metabolism were not affected by GH treatment in patients with ISS. There was no significant GH effect on fasting blood glucose in either study (GH dose range, 0.22-0.37 mg/kg.wk) or on insulin sensitivity (placebo-controlled study only). GH appears safe in ISS; however, the studies were not powered to assess the frequency of rare GH-related events, and longer-term follow-up studies of GH-treated patients with ISS are warranted.

Growth hormone treatment of idiopathic short stature.

Considerable controversy exists about the use of growth hormone (GH) treatment in short children without classical GH deficiency (idiopathic short stature or ISS). ISS is a multifactorial disorder with many potential causes rather than a single diagnostic entity, and it is in essence a diagnosis of exclusion. A careful investigation of the components of the GH/insulin-like growth factor (IGF) axis and other potential causes of short stature must be carried out in patients with significant short stature before they are categorized as having the ISS syndrome. As a group, most patients with ISS can be expected to attain an adult stature within the normal range. The ISS patients who will not do so are generally those who have a poor initial predicted adult height (PAH) and present at a younger age. Those ISS patients with a shorter midparental height are also less likely to achieve a normal adult height. In addition, several studies have shown that, as a group, males with ISS do not attain their initial PAH. Most studies on the GH treatment of patients with ISS have shown a short-term increase in growth rate and relative height. However, the long-term outcome of GH treatment of ISS has been variously reported to be no significant change, a slight increase, or a significant increase. One of the largest and most optimistic experiences with GH treatment of ISS is the collaborative US study sponsored by Genentech. This group has treated 121 patients with ISS not due to classically defined GH deficiency for up to 9 years with GH (0.3 mg/kg per week). A total of 51 of these patients has now reached near final height, with bone age (BA) > or = 16 years for boys and > or = 14 years for girls. The mean difference between the first available pretreatment PAH and the PAH at near-final height (delta PAH) was 5.7 cm for the boys and 6.5 cm for the girls. The strongest predictors of response to treatment available before the start of GH treatment were bone age and pretreatment PAH. The increase in height seen with GH treatment of ISS was not enough to increase the mean expected final height to the midparental target height, or to completely correct a low pretreatment PAH. Whether this increase in expected final height in ISS patients with GH treatment is due to a correction of a subtle abnormality of GH secretion or action, or to the pharmacological effects of GH is unclear. The decision to use GH treatment in ISS is a complex issue which must involve the accuracy of the diagnosis of GH deficiency or abnormality in the GH/IGF axis, the PAH and BA of the patient, the potential benefits, and economic issues for the medical care system. In general, GH treatment should only be considered in young ISS patients with poor initial PAH and height prognosis, and GH treatment of older patients who have a normal PAH is not justified.

Growth hormone treatment of idiopathic short stature: a controlled study in a wel‐defined population

Growth hormone treatment of idiopathic short stature: a controlled study in a wel‐defined population

Growth hormone treatment of idiopathic short stature: analysis of the database from KIGS, the Kabi Pharmacia International Growth Study

Within the Kabi Pharmacia International Growth Study (KIGS) database, there is information on 1017 (700 male/317 female) patients with idiopathic short stature (ISS). These patients were started on recombinant human growth hormone (GH) at a median age of 10.8 years, a bone age of -1.8 SDS, a height of -2.6 SDS and a predicted adult height (PAH) (Bailey-Pinneau method) of -2.5 SDS. The median dose of GH was 0.6 IU/kg body weight/week and the frequency of injections was six/week. According to the relationship with target height the patients were classified into 'familial short stature (FSS)' (height SDS > target height SDS -1.28) and into 'non-FSS' (height SDS < target height SDS -1.28). During the first year of GH treatment there was an overall increment in the median height velocity from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross-sectional analysis demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive correlation between gain in PAH and the GH dose (n = 202, r = 0.18, p < 0.01) during the first year. Longitudinal analysis in 84 patients showed an overall increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS first-year prediction model for patients with idiopathic GH deficiency on cohorts of prepubertal children with FSS and non-FSS, a lower responsiveness to GH in the non-FSS group was observed. It is concluded that higher than substitutive doses of GH are required for the long-term improvement of growth in ISS.