problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201056614-23problendo-4720Research ArticleСтатьиArticlesЭффективность и безопасность применения рекомбинантного гормона роста у детей с идиопатической низкорослостьюThe efficacy and safety of recombinant growth hormone in children with idiopathic short stature (two-year experience)ShandinA Nalex_shandin@mail.ruNagaevaE V-PeterkovaV A-DedovI I-201015122010566ТОМ 56, №6 (2010)1423Copyright © Shandin A.N., Nagaeva E.V., Peterkova V.A., Dedov I.I., 20102010Shandin A.N., Nagaeva E.V., Peterkova V.A., Dedov I.I.Shandin A.N., Nagaeva E.V., Peterkova V.A., Dedov I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/4720

Работа выполнена в рамках Федеральной целевой программы "Научные и научно-педагогические кадры инновационной России на 2009-2013 гг.". Оценивали эффективность и безопасность терапии рекомбинантным гормоном роста (рГР) у детей с идиопатической низкорослостью, а также анализировали факторы, влияющие на эффективность терапии. Проведено обследование 93 пациентов с идиопатической низкорослостью в возрасте от 3 до 12 лет. Все пациенты были разделены на 3 группы: 1-я (n=38) получала рГР в дозе 0,033 мг/кг/сут, 2-я (n=18) - в дозе 0,05 мг/кг/сут, 3-я (n=37) - контрольная. Длительность терапии составляла 6 мес у 56 детей, 12 мес - у 41, 18 мес - у 24 и 24 мес - у 18. На фоне лечения оценивали изменения костного возраста, динамику уровня инсулиноподобного фактора роста 1 (ИФР-1), показателей углеводного, липидного, фосфорно-кальциевого обмена, а также функции печени, почек и щитовидной железы. На 1-м году лечения скорость роста повысилась с 4,5±1,2 до 7,9±1,5 см/год (при дозе 0,033 мг/кг/сут) и до 9,1±1,5 см/год (0,05 мг/кг/сут), на 2-м году терапии скорость роста составляла 7,1±1,4 и 7,9±1,6 см/год соответственно. При этом наблюдалось значительное улучшение ростовых показателей. ΔSDS роста за 1 год терапии составила 0,56±0,28 (0,033 мг/кг/сут) и 0,71±0,22 (0,05 мг/кг/сут), за 2 года лечения суммарная ΔSDS роста составила 0,94±0,29 и 1,06±0,67 соответственно. В контрольной группе скорость роста и степень отставания в росте существенно не изменились. Выявлены корреляционные взаимосвязи скорости роста на фоне лечения с возрастом начала терапии (r=–0,28, p=0,045; n=56) и дозой рГР (r=0,32, p=0,043; n=41), а также ΔSDS роста с возрастом начала терапии (r=–0,50, p=0,0002; n=56). Через 6 мес результатом лечения стало достижение границ нормального роста (>–2 SDS) у 21% детей, через 1 год - у 30% и через 2 года - у 37%. В то же время в контрольной группе нормализации роста не наблюдалось ни у одного ребенка. У части детей наблюдалось ускорение темпов костного созревания, однако прогнозируемый рост (по Bayley-Pinneau) улучшился. Уровень ИФР-1 на фоне лечения значительно повысился, оставаясь в пределах нормальных значений, корреляции между ним и эффективностью терапии не получено. Не наблюдалось значимых изменений со стороны показателей углеводного, липидного, фосфорно-кальциевого обмена, а также функции печени, почек и щитовидной железы. Таким образом, ростостимулирующая терапия рГР у детей с идиопатической низкорослостью в расчетных дозах 0,033-0,05 мг/кг/сут значительно повышает скорость роста и улучшает ростовые показатели. Главными факторами, определяющими эффективность терапии, являются возраст начала лечения и расчетная доза рГР.

This study was designed to evaluate the efficacy and safety of the treatment of children with idiopathic short stature using recombinant growth hormone (rGH); in addition, the factors influencing its therapeutic efficiency were analysed. A total of 93 patients aging from 3 to 12 years were available for the observation. They were divided into three groups. The children in group 1 (n=38 ) were given rGH at a dose of 0.033 mg/kg/24 hours and in group 2 (n=18 ) at 0.05 mg/kg/24 hr; the control group 3 was comprised of 37 children. The duration of therapy was 6 months in 56 children, 12 months in 41, 18 months in 24, and 24 months in 18 children. The end points of the study were bone age variations; dynamics of insulin-like growth factor-1 levels; characteristics of carbohydrate, lipid, and phosphorus-calcium metabolism; hepatic, renal, and thyroid function. The growth rate within the first year after the onset of the treatment increased from 4.5±1.2 to 7.9±1.5 cm/year in group 1 (0.033 mg/kg/24 hours) and from 9.1±1.5 cm/year in group 2 (0.05 mg/kg/24 hr). In the second year, the growth rate under effect of the same GH doses was 7.1±1.4 and 7.9±1.6 cm/year respectively. The total growth rate ΔSDS for the first year of therapy was 0,56±0,28 (0,033 mg/kg/24 hr) and 0,71±0,22 (0,05 mg/kg/24 hr), the respective ΔSDS values in the second year were 0,94±0,29 and 1,06±0,67. Neither the growth rate nor the failure to thrive changed significantly in the control group. The growth rate in the treated children correlated with their age at the onset of therapy (r = –0.28, p= –0.045; n=56) and the dose of GH (r=0.32, p<=0.043; n=41); in addition, there was correlation between the growth rate ΔSDS values and the age at the onset of therapy (r=–0.50, p=0.0002; n=56). 21% of the children reached the normal growth range (>–2ΔSDS) 6 months after the beginning of therapy, 30% and 37% after 1 and 2 years respectively. None of the patients in the control group showed the normal growth. Some of them underwent accelerated bone maturation, and their growth prognosis (calculated according to Bayley-Pinneau) was improved. The IGF-1 level in the treated patients increased within the normal range but did not correlate with the efficacy of therapy. Nor were apparent changes recorded in the characteristics of carbohydrate, lipid, and phosphorus-calcium metabolism. It is concluded that the growth-stimulating treatment of children with idiopathic short stature using rGH at a dose range from 0.033 to 0.05 mg/kg/24 hours significantly increased the growth rate and dynamics. The main factors determining the therapeutic efficacy of rGH are the age of the patients at which the treatment is initiated and the calculated rGH dose.

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The authors declare that there are no conflicts of interest present.