Effect of Long-Term Recombinant Growth Hormone Therapy in Children - The National Cooperative Growth Study, USA, 1985-1994

Abstract

Over a 9-year period (1985-1994) approximately 20,000 children received recombinant human growth hormone (rhGH) while enrolled in the National Cooperative Growth Study (NCGS), an observational, longitudinal study designed to monitor the long term efficacy and safety of rhGH administered to children in North America. Forty-four percent of the patients had idiopathic growth hormone deficiency (IGHD), 13.8% organic GHD (OGHD), 25% idiopathic short stature (ISS), 9.9% Turner's syndrome (TS), and 7.3% miscellaneous disorders. Eighty-five percent of the patients enrolled were Caucasian, and approximately two-thirds of the non-Turner patients were male. For the subset of patients treated for at least 4 years and who were prepubertal throughout this period (IGHD N=308, OGHD N=93, ISS N=169, TS N=82), mean growth rates increased in all patient categories and remained at or above pretreatment growth rates through 4 consecutive years of therapy with rhGH. Growth rates during administration of rhGH were greater in children in whom the pretreatment maximum stimulated GH concentration was < or =3 microg/l. Patients treated with 6 or 7 doses of rhGH each week grew more rapidly than did those receiving thrice weekly dosages, although the ratios of the increment in bone age to the increment in height age after two years of therapy were similar in the two treatment regimens. For patients treated with rhGH for 7 consecutive years, the mean height standard deviation scores increased by 2.5 in IGHD (N=169), 2.0 in OGHD (N=50), 1.9 in ISS (N=69), and 1.3 in TS (N=19), but remained below target heights in all categories. It is concluded that administration of rhGH increases growth rates in patients with IGHD, OGHD, ISS, and TS, and that this stimulatory effect can persist for at least 4 years.

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

“…Physiological rhGH replacement in GH-deficient adults requires approximately one-third to one-fifth of the dose used in this study (21). Despite the high rhGH doses, we observed few of the side effects previously described in adults with GH deficiency (22,23). However, a high frequency of diarrhea was seen, particularly after administration of the high rhGH dose.…”

A Multicenter Study of the Efficacy and Safety of Sustained Release GH in the Treatment of Naive Pediatric Patients with GH Deficiency

“…With the greater availability of rhGH, the frequency of administration has increased from three to seven injections per wk to maximize growth. In addition, the average GH dosage in the United States has increased to approximately 0.3 mg/kg⅐wk (1)(2)(3). Administration was made more convenient with the evolution from im to sc injections.…”

The Role of the Pituitary-Growth Hormone-IGF Axis in Glucose Homeostasis

“…Idiopathic isolated GH deficiency is the most common form of GH deficiency, accounting for as many as 44% of patients treated with growth hormone (Root, Kemp et al 1998). Because GH is secreted episodically and GH is present in the serum for only about 20 minutes after it is secreted, random assessment of serum GH levels is rarely helpful.…”