Indian J Pediatr DOI 10.1007/s12098-015-1746-y
ORIGINAL ARTICLE
Efficacy and Safety of Human Growth Hormone in Idiopathic Short Stature Songxue Tao 1,2 & Guimei Li 1 & Qian Wang 1 & Yanyan Hu 1
Received: 6 November 2014 / Accepted: 12 March 2015 # Dr. K C Chaudhuri Foundation 2015
Abstract Objective To explore the efficacy and safety of medium dose of recombinant human growth hormone (rhGH) in the treatment of prepubescent girls with idiopathic short stature (ISS). Methods Fifty-one prepubescent girls with ISS were recruited into the study and divided into the treatment group (n=27) and the control group (n=24) depending on whether or not they accepted rhGH therapy respectively. A therapeutic dose of 0.35–0.42 mg of rhGH·(kg·wk)−1 was administered for 2 y. The control group patients did not receive rhGH treatment. The height, growth rate, height standard deviation score (HtSDS), bone age (BA), the expected adult height (PAH), and potential side effects of rhGH treatment were analysed and compared between the groups. Results The growth rate and htSDS during years 1 and 2 were significantly higher in the treatment group than in the control group. The expected adult height was significantly higher after 2 y of treatment as compared to the corresponding value in the control group. The BA after years 1 and 2 did not significantly differ between the two groups. Conclusions Thus, short-term therapy with a medium dose of rhGH was found to have a precise effect on prepubertal children with ISS. At this dose, it can significantly increase the growth rate of children and improve the expected adult height without accelerating bone maturation. No serious adverse
* Guimei Li [email protected] 1
Department of Pediatrics, Shandong Provincial Hospital affiliated to Shandong University, 9677 Jingshi Road, Jinan 250014, People’s Republic of China
2
Department of Pediatrics, Anhui Provincial Hospital, Hefei, China
reactions were found in association with rhGH use during the two-year study period. Keywords Recombinant human growth hormone . Idiopathic short stature . Preadolescence . Growth hormone therapy
Introduction Idiopathic short stature (ISS) is one of the common causes of short stature. It is defined as a kind of symmetrical short stature whose cause has not yet been determined, and if this condition is left untreated, the final height of the individual will be below the normal height range. In July 2003, the US FDA approved the use of recombinant human growth hormone (rhGH) to treat children with ISS [1]. Studies conducted both in China, in India [2] and internationally disagree on the ideal dose for the treatment of ISS. The FDA has recommended a therapeutic dose of 0.30–0.37 mg rhGH·(kg·wk)−1 [3]. In an international study, Wit et al. had compared the therapeutic efficacy of different doses of GH in ISS, and found that the growth-promoting effect of rhGH was dose-dependent, and a more obvious improvement on the final height could be observed with increased dose [4]. Another study reported that treatment with a high dose of rhGH [0.45–0.52 mg rhGH·(kg· wk)−1] showed no increase in adult height as a result of the appearance of bone age (BA) and early puberty [5]. Therefore, researchers are currently focusing on how to determine the optimal dose to treat ISS with efficacy and safety. In 2008, the Chinese Society of Pediatric Endocrinology and Metabolism recommended a dose of 0.35–0.46 mg rhGH·(kg·wk)−1 [6], and a Chinese study reported the treatment of ISS with rhGH, but there was no control group and a short observation time (10 μg/L; birth with normal length, weight, and symmetrical figure; complete clinical and laboratory data. Patients suffering from systemic, nutritional diseases; other endocrine, metabolic, genetic, or chromosomal disorders that may affect growth; and those who already showed signs of puberty were excluded from the study. After applying the above mentioned inclusion and exclusion criteria, a total of 51 pre-adolescent girls were selected for participation in the study. The average age of the participants was 6.74 (range, 3–10) y. The 51 children with ISS were divided into two groups: a test group consisting of 27 patients, who opted to receive the rhGH treatment (provided by Changchun JinLei SaiZeng Co.), and a control group, who opted not to receive the rhGH treatment citing economic or other reasons but agreed to a regular patient follow-up. Informed consents were obtained from all children and their parents. All patients underwent measurements for height and weight, developmental assessments, and BA status before treatment, and were followed up by the same person and using the same instrument. The Chinese standards for children’s height (2005) were adopted as the height assessment criteria. Secondary sex characteristics were assessed according to the Tanner stage, and patients with breasts at the B2 stage were considered as having entered pubertal development. The target height (TH) was calculated as the average height of the father and mother minus 6.5 cm. The BA was assessed according to RUS-CHN method (the standards of skeletal maturity of hand and wrist for Chinese – China 05). Over the 2-y treatment period, a follow-up visit occurred every 3 mo to assess thyroid function, insulin-like growth factor-1 (IGF-1) level, fasting blood glucose, and biochemistry, and condition of the injection site was observed. The BA was rechecked every 6 mo. At the same time, the children were provided reasonable guidance on health parameters such as diet, exercise, and sleep. Domestic rhGH therapy was used uniformly for all the participants, who received a weekly dose of 0.35–0.42 mg·(kg.wk)−1, and a subcutaneous
injection of 50–60 μg·(kg·d)−1 every night before bedtime. The injection sites were around the umbilicus, the middle and lateral side of the thighs, and the upper and lateral sides of the upper arms throughout the entire 2 y of treatment. Evaluation indicators included height (Ht), height standard deviation score (HtSDS), GV, BA, and PAH. SPSS 17.0 statistical software was used for data processing. All the data are presented as x ± s, using the t test. P
ORIGINAL ARTICLE
Efficacy and Safety of Human Growth Hormone in Idiopathic Short Stature Songxue Tao 1,2 & Guimei Li 1 & Qian Wang 1 & Yanyan Hu 1
Received: 6 November 2014 / Accepted: 12 March 2015 # Dr. K C Chaudhuri Foundation 2015
Abstract Objective To explore the efficacy and safety of medium dose of recombinant human growth hormone (rhGH) in the treatment of prepubescent girls with idiopathic short stature (ISS). Methods Fifty-one prepubescent girls with ISS were recruited into the study and divided into the treatment group (n=27) and the control group (n=24) depending on whether or not they accepted rhGH therapy respectively. A therapeutic dose of 0.35–0.42 mg of rhGH·(kg·wk)−1 was administered for 2 y. The control group patients did not receive rhGH treatment. The height, growth rate, height standard deviation score (HtSDS), bone age (BA), the expected adult height (PAH), and potential side effects of rhGH treatment were analysed and compared between the groups. Results The growth rate and htSDS during years 1 and 2 were significantly higher in the treatment group than in the control group. The expected adult height was significantly higher after 2 y of treatment as compared to the corresponding value in the control group. The BA after years 1 and 2 did not significantly differ between the two groups. Conclusions Thus, short-term therapy with a medium dose of rhGH was found to have a precise effect on prepubertal children with ISS. At this dose, it can significantly increase the growth rate of children and improve the expected adult height without accelerating bone maturation. No serious adverse
* Guimei Li [email protected] 1
Department of Pediatrics, Shandong Provincial Hospital affiliated to Shandong University, 9677 Jingshi Road, Jinan 250014, People’s Republic of China
2
Department of Pediatrics, Anhui Provincial Hospital, Hefei, China
reactions were found in association with rhGH use during the two-year study period. Keywords Recombinant human growth hormone . Idiopathic short stature . Preadolescence . Growth hormone therapy
Introduction Idiopathic short stature (ISS) is one of the common causes of short stature. It is defined as a kind of symmetrical short stature whose cause has not yet been determined, and if this condition is left untreated, the final height of the individual will be below the normal height range. In July 2003, the US FDA approved the use of recombinant human growth hormone (rhGH) to treat children with ISS [1]. Studies conducted both in China, in India [2] and internationally disagree on the ideal dose for the treatment of ISS. The FDA has recommended a therapeutic dose of 0.30–0.37 mg rhGH·(kg·wk)−1 [3]. In an international study, Wit et al. had compared the therapeutic efficacy of different doses of GH in ISS, and found that the growth-promoting effect of rhGH was dose-dependent, and a more obvious improvement on the final height could be observed with increased dose [4]. Another study reported that treatment with a high dose of rhGH [0.45–0.52 mg rhGH·(kg· wk)−1] showed no increase in adult height as a result of the appearance of bone age (BA) and early puberty [5]. Therefore, researchers are currently focusing on how to determine the optimal dose to treat ISS with efficacy and safety. In 2008, the Chinese Society of Pediatric Endocrinology and Metabolism recommended a dose of 0.35–0.46 mg rhGH·(kg·wk)−1 [6], and a Chinese study reported the treatment of ISS with rhGH, but there was no control group and a short observation time (10 μg/L; birth with normal length, weight, and symmetrical figure; complete clinical and laboratory data. Patients suffering from systemic, nutritional diseases; other endocrine, metabolic, genetic, or chromosomal disorders that may affect growth; and those who already showed signs of puberty were excluded from the study. After applying the above mentioned inclusion and exclusion criteria, a total of 51 pre-adolescent girls were selected for participation in the study. The average age of the participants was 6.74 (range, 3–10) y. The 51 children with ISS were divided into two groups: a test group consisting of 27 patients, who opted to receive the rhGH treatment (provided by Changchun JinLei SaiZeng Co.), and a control group, who opted not to receive the rhGH treatment citing economic or other reasons but agreed to a regular patient follow-up. Informed consents were obtained from all children and their parents. All patients underwent measurements for height and weight, developmental assessments, and BA status before treatment, and were followed up by the same person and using the same instrument. The Chinese standards for children’s height (2005) were adopted as the height assessment criteria. Secondary sex characteristics were assessed according to the Tanner stage, and patients with breasts at the B2 stage were considered as having entered pubertal development. The target height (TH) was calculated as the average height of the father and mother minus 6.5 cm. The BA was assessed according to RUS-CHN method (the standards of skeletal maturity of hand and wrist for Chinese – China 05). Over the 2-y treatment period, a follow-up visit occurred every 3 mo to assess thyroid function, insulin-like growth factor-1 (IGF-1) level, fasting blood glucose, and biochemistry, and condition of the injection site was observed. The BA was rechecked every 6 mo. At the same time, the children were provided reasonable guidance on health parameters such as diet, exercise, and sleep. Domestic rhGH therapy was used uniformly for all the participants, who received a weekly dose of 0.35–0.42 mg·(kg.wk)−1, and a subcutaneous
injection of 50–60 μg·(kg·d)−1 every night before bedtime. The injection sites were around the umbilicus, the middle and lateral side of the thighs, and the upper and lateral sides of the upper arms throughout the entire 2 y of treatment. Evaluation indicators included height (Ht), height standard deviation score (HtSDS), GV, BA, and PAH. SPSS 17.0 statistical software was used for data processing. All the data are presented as x ± s, using the t test. P
