SOMATOTROP YETISHMOVCHILIGI BOR BOLALARDA SINTETIK SOMATOTROPIN ANALOGLARI FONIDA BO'Y O'SISH DINAMIKASI

ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 781 UDK: 616.432-053.2 SOMATOTROP YETISHMOVCHILIGI BOR BOLALARDA SINTETIK SOMATOTROPIN ANALOGLARI FONIDA BO’Y O'SISH DINAMIKASI Zubayda Xalbayeva -assistent, Department of Endocrinologi, Samarkand State Medical University, Samarkand , Republic of Uzbekistan Email: zubay[email protected] Orcid ID: 0009-0005-4358-9489 Annotatsiya Somatotrop yetishmovchiligi (SY), shuningdek, growth hormone deficiency (GHD) nomi bilan ma'lum, bolalarda o'sish gormonining yetarli darajada ishlab chiqarilmasligi bilan bog'liq endokrin kasallik bo'lib, bu holat bo'y o'sishining sekinlashuviga, yakuniy bo'yining past bo'lishiga va psixososial rivojlanishdagi muammolarga olib keladi. Sintetik somatotropin analoglari, xususan rekombinant inson o'sish gormoni (rhGH), bu kasallikni davolashda asosiy usul hisoblanadi va bolalarning bo'y o'sish dinamikasini sezilarli darajada yaxshilaydi. Ushbu obzor maqola PubMed, PMC, Scopus va boshqa yuqori indekslangan ma'lumotlar bazalaridagi so'nggi sistematik obzorlar, meta-tahlillar va klinik tadqiqotlardan foydalangan holda, rhGH ning bolalardagi bo'y o'sish dinamikasiga, jumladan o'sish tezligi (height velocity, HV), bo'y standart deviyatsiya skori (height SDS, HSDS) va yakuniy kattalar bo'yiga (adult height, AH) ta'sirini batafsil tahlil qiladi. Natijalar shuni ko'rsatadiki, davolashning birinchi yilida HV o'rtacha 8-12 sm/yilga yetishi mumkin, keyingi yillarda esa 4-7 sm/yilga pasayadi, bu normal o'sish tezligiga yaqinlashadi. Yakuniy AH SDS treated guruhda o'rtacha -2,5 dan -0,3 ga yaqinlashadi, bu normal diapazonga (0 ± 2 SDS) yaqinlashishni anglatadi va untreated guruhga nisbatan 4-8 sm farqni ta'minlaydi. Yuqori dozalar (0,025-0,07 mg/kg/hafta) samaraliroq bo'lib, ammo individual omillar, masalan, yosh (davolashni erta boshlash yaxshiroq natija beradi), boshlang'ich bo'y SDS, pubertal holat, suyak yoshi (bone age), metabolik ko'rsatkichlar (insulin qarshiligi, tiroid gormonlari, hemoglobin, IGF-1 darajasi) va genetik faktorlar (masalan, GH1 geni mutatsiyalari) ta'sir qiladi. Davolash xavfsizligi yuqori, jiddiy nojo'ya ta'sirlar (masalan, intrakranial gipertenziya, neoplazma rivojlanishi) kam (1-2% dan kam), ammo in'ektsiya joyidagi lokal reaktsiyalar va vaqtinchalik IGF-1 oshishi tez-tez uchraydi. Ushbu obzor rhGH ning qisqa muddatli (birinchi 6-12 oy) va uzoq muddatli (5-10 yil) natijalarini, shuningdek, kunlik va haftalik (pegylated) dozalash usullarini taqqoslaydi, GHD va idiopathic short stature (ISS) o'rtasidagi farqlarni ko'rib chiqadi (GHD da natijalar 20-30% yaxshiroq). Bundan tashqari, davolashning farmakoekonomik jihatlari (xarajat-samaradorlik), monitoring usullari (IGF-1 va IGFBP-3 o'lchovlari, suyak yoshi rentgeni) va kelajakdagi tadqiqot yo'nalishlari (gen terapiyasi, yangi LAGH formulalari) muhokama qilinadi. Obzor 1990-2025 yillardagi 100 dan ortiq tadqiqotni qamrab oladi va pediatrik endokrinologlar uchun klinik amaliyot bo'yicha batafsil tavsiyalar beradi, jumladan dozani individualizatsiya qilish va davolash muddatini optimallashtirish. Kalit so'zlar: rekombinant o'sish gormoni, bolalarda bo'y o'sishi, o'sish dinamikasi, yakuniy bo'y, davolash samaradorligi, gormon yetishmovchiligi, height velocity, height SDS, metabolik omillar, insulin qarshiligi, tiroid funktsiyasi, dose-response. ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 782 СОМАТОТРОПНАЯ НЕДОСТАТОЧНОСТЬ У ДЕТЕЙ: ДИНАМИКА РОСТА НА ФОНЕ СИНТЕТИЧЕСКИХ АНАЛОГОВ СОМАТОТРОПИНА Зубайда Халабаева - ассистент, кафедра эндокринологии, Самаркандский государственный медицинский университет, Самарканд, Республика Узбекистан Email: zubay[email protected] Orcid ID: 0009-0005-4358-9489 Аннотация Соматотропная недостаточность (СН), также известная как дефицит роста (GHD), представляет собой эндокринное заболевание, связанное с недостаточным производством гормона роста у детей, что приводит к замедлению роста, низкому конечному росту и проблемам с психосоциальным развитием. Синтетические аналоги соматотропина, в частности рекомбинантный человеческий гормон роста (rhGH), являются основным методом лечения этого заболевания и значительно улучшают динамику роста детей. Эта обзорная статья использует недавние систематические обзоры, мета-анализы и клинические исследования из баз данных PubMed, PMC, Scopus и других высоко индексированных источников, чтобы детально проанализировать влияние rhGH на динамику роста у детей, включая скорость роста (height velocity, HV), стандартный отклонение роста (height SDS, HSDS) и конечный рост у взрослых (adult height, AH). Результаты показывают, что в первый год лечения HV может достигать в среднем 8-12 см/год, а на последующие годы снижаться до 4-7 см/год, что приближается к нормальной скорости роста. Конечный AH SDS в группе с лечением приближается в среднем от -2,5 до -0,3, что указывает на приближение к нормальному диапазону (0 ± 2 SDS) и обеспечивает разницу в 4-8 см по сравнению с группой без лечения. Более высокие дозы (0,025-0,07 мг/кг/неделя) более эффективны, однако индивидуальные факторы, такие как возраст (раннее начало лечения дает лучшие результаты), начальный SDS роста, половое созревание, возраст костей (bone age), метаболические показатели (инсулинорезистентность, уровни тиреоидных гормонов, гемоглобина, IGF-1) и генетические факторы (например, мутации гена GH1) влияют на это. Безопасность лечения высока, серьезные побочные эффекты (например, внутричерепная гипертензия, развитие неоплазм) встречаются редко (менее 1-2%), однако локальные реакции в местах инъекций и временное повышение IGF-1 встречаются часто. Этот обзор сравнивает краткосрочные (первые 6-12 месяцев) и долгосрочные (5-10 лет) результаты, а также методы дозирования (ежедневное и недельное (пегилированное)) и рассматривает различия между GHD и идиопатической низкорослостью (ISS) (результаты при GHD на 20-30% лучше). Кроме того, обсуждаются фармакоэкономические аспекты лечения (стоимость-эффективность), методы мониторинга (измерения IGF-1 и IGFBP-3, рентгенография возраста костей) и направления будущих исследований (генотерапия, новые формулы LAGH). Обзор охватывает более 100 исследований за период с 1990 по 2025 годы и дает подробные рекомендации по клинической практике для педиатрических эндокринологов, включая индивидуализацию дозировки и оптимизацию продолжительности лечения. Ключевые слова: рекомбинантный гормон роста, рост у детей, динамика роста, конечный рост, эффективность лечения, гормональная недостаточность, скорость роста, SDS ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 783 роста, метаболические факторы, инсулинорезистентность, функции щитовидной железы, доза-ответ. SOMATOTROPIC DEFICIENCY IN CHILDREN: GROWTH DYNAMICS ON SYNTHETIC SOMATOTROPIN ANALOGS Zubayda Khalbaeva - Assistant, Department of Endocrinology, Samarkand State Medical University, Samarkand, Republic of Uzbekistan Email: zubay[email protected] Orcid ID: 0009-0005-4358-9489 Abstract Somatotropic deficiency (SD), also known as growth hormone deficiency (GHD), is an endocrine disorder associated with insufficient production of growth hormone in children, leading to slowed growth, low final height, and psychosocial development issues. Synthetic somatotropin analogs, particularly recombinant human growth hormone (rhGH), are the main method for treating this condition and significantly improve the growth dynamics of children. This review article utilizes recent systematic reviews, meta-analyses, and clinical studies from databases such as PubMed, PMC, Scopus, and other high-index sources to provide a detailed analysis of the effects of rhGH on growth dynamics in children, including growth velocity (height velocity, HV), height standard deviation score (height SDS, HSDS), and adult height (AH). Results indicate that in the first year of treatment, HV can average between 8-12 cm/year, decreasing to 4-7 cm/year in subsequent years, approaching normal growth velocity. The final AH SDS in the treated group approaches an average of -2.5 to - 0.3, indicating closeness to the normal range (0 ± 2 SDS) and providing a difference of 4-8 cm compared to the untreated group. Higher doses (0.025-0.07 mg/kg/week) are more effective, but individual factors such as age (earlier treatment yields better outcomes), initial height SDS, pubertal status, bone age, metabolic parameters (insulin resistance, thyroid hormones, hemoglobin, IGF-1 levels), and genetic factors (e.g., GH1 gene mutations) also have an impact. Treatment safety is high, with serious adverse effects (e.g., intracranial hypertension, neoplasm development) occurring infrequently (less than 1-2%), although local reactions at injection sites and temporary increases in IGF-1 are common. This review compares short-term (first 6-12 months) and long-term (5-10 years) results, as well as daily and weekly (pegylated) dosing methods, and examines differences between GHD and idiopathic short stature (ISS) (with results in GHD being 20-30% better). Additionally, pharmacoeconomic aspects of treatment (cost-effectiveness), monitoring methods (measurements of IGF-1 and IGFBP-3, bone age X-rays), and future research directions (gene therapy, new LAGH formulations) are discussed. The review encompasses over 100 studies from 1990 to 2025 and provides detailed recommendations for clinical practice for pediatric endocrinologists, including dose individualization and treatment duration optimization. Keywords: recombinant growth hormone, growth in children, growth dynamics, final height, treatment effectiveness, hormone deficiency, height velocity, height SDS, metabolic factors, insulin resistance, thyroid function, dose-response. ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 784 Kirish Somatotrop yetishmovchiligi (SY), yoki growth hormone deficiency (GHD), gipofiz bezi oldingi qismi tomonidan o'sish gormonining (GH) yetarli darajada ishlab chiqarilmasligi bilan tavsiflanadigan endokrin kasallikdir [1] [2]. Bu holat bolalarning bo'y o'sishini sekinlashtiradi, yakuniy bo'yini normaldan 2-4 standart deviyatsiya (SDS) past qiladi va psixososial muammolarga, masalan, o'zini past baholash, depressiya va ijtimoiy izolyatsiyaga olib keladi [3] [4]. SY ning epidemiologiyasi: bolalarning 1:3000-1:10,000 tasida uchraydi, ko'pincha idiopatik (sababi noma'lum, 70-80%), ammo tug'ma (genetik mutatsiyalar, masalan, GH1, PROP1 genlari) yoki orttirilgan omillar (miya travmalari, nurlanish terapiyasi, infeksiyalar) bilan bog'liq bo'lishi mumkin [5]. Kasallikning patofiziologiyasi: GH yetishmasligi jigar va boshqa to'qimalarda insulin-o'xshash o'sish faktori-1 (IGF-1) ishlab chiqarilishini pasaytiradi, bu esa o'sish plitalarining (epifiz plitalari) faoliyatini buzadi va suyak elongatsiyasini kamaytiradi [6]. Bundan tashqari, GH metabolizmga ta'sir qiladi: yog' to'qimalarini kamaytiradi, mushak massasini oshiradi va suyak zichligini saqlaydi, shuning uchun yetishmaslik metabolik sindromga (insulin qarshiligi, dislipidemiya) olib kelishi mumkin [7]. Tarixiy jihatdan, 1958-yilda hayvoniy (chorva) GH dan foydalanilgan, ammo 1985-yilda rekombinant texnologiya bilan rhGH ishlab chiqarilishi (Genentech kompaniyasi tomonidan) xavfsiz va samarali davolashni ta'minladi, bu Creutzfeldt-Jakob kasalligi xavfini yo'qotdi [8]. rhGH ning maqsadlari: bolalarning bo'yini pubertal davrda normallashtirish (target height ga yaqinlashish), yakuniy bo'yni -1 SDS ga yaqinlashtirish va metabolik holatni yaxshilash [9]. So'nggi tadqiqotlar haftalik pegylated rhGH (LAGH, masalan, Somatrogon, Lonapegsomatropin) va kunlik rhGH ni taqqoslab, haftalik usulning bemor qulayligini (kamroq in'ektsiyalar) va shunga yaqin samaradorligini ko'rsatmoqda, ammo LAGH da IGF-1 darajasi yuqoriroq bo'lishi mumkin [9,10]. Metabolik omillar, masalan, insulin qarshiligi (HOMA-IR indeksi), tiroid gormonlari (FT4, TSH), hemoglobin va vitamin D darajasi davolash natijalariga ta'sir qiladi, shuning uchun individual yondashuv (dozani moslashtirish) zarur. GHD va ISS o'rtasidagi farq: GHD da GH provokatsiya testida peak GH <7-10 ng/mL, ISS da normal GH ammo qisqa bo'y, natijada GHD da rhGH samarasi yuqoriroq [10]. Ushbu obzor rhGH ning bo'y o'sish dinamikasiga, shu jumladan HV, HSDS, AH, metabolik va psixososial ta'siriga yuqori dolzarblikdagi manbalardan tahlil qiladi, klinik protokollar va kelajakdagi tadqiqotlar bo'yicha tavsiyalar beradi. Material va metodlar Ushbu obzor PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) yo'riqnomasiga muvofiq sistematik obzor usulida amalga oshirildi. PubMed, PMC, Scopus, Web of Science, Cochrane Library va Google Scholar kabi bazalarda "growth hormone deficiency children recombinant GH treatment height growth dynamics efficacy safety metaanalysis", "rhGH height velocity SDS adult height metabolic factors", "long-acting GH vs daily GH children GHD" kabi kalit so'zlar va MeSH terminlari bilan qidiruv o'tkazildi. 1990-2025 yillardagi 150 dan ortiq natija ko'rib chiqildi, yuqori impakt-faktorli jurnallardagi (masalan, Journal of Clinical Endocrinology & Metabolism, Hormone Research in Paediatrics, European Journal of Endocrinology, Frontiers in Endocrinology) randomized nazorat ostidagi tadqiqotlar (RCT), prospektiv kohort tadqiqotlari, retrospektiv tahlillar va meta-tahlillar tanlandi. Inclusion kriteriyalari: bolalardagi SY (peak GH <10 ng/mL provokatsiya testida), rhGH bilan davolash (kunlik 0,025-0,05 mg/kg/hafta yoki haftalik ekvivalenti), o'sish parametrlari (HV, HSDS, AH, bone age) haqida batafsil ma'lumotlar, ingliz tilida chop etilgan, kamida 20 bemorlik guruh, davolash muddati kamida 12 oy. Exclusion kriteriyalari: kattalar yoki boshqa indikatsiyalar (masalan, Turner sindromi, Prader-Willi), ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 785 hayvoniy modellari, faqat qisqa muddatli (<6 oy) natijalar, past sifatli tadqiqotlar (Jadad skalasi <3). Ma'lumotlar ekstraktsiyasi: o'rtacha qiymatlar, standart deviyatsiyalar (SD), korrelyatsiya koeffitsientlari (r), p-qiymatlar va effekt o'lchovlari (mean difference, MD; odds ratio, OR) yig'ildi. Statistika tahlili: t-test, ANOVA, Kruskal-Wallis testlari, lineyniy va logistika regressiya modellaridan foydalanildi (R 4.3.1 va SPSS 28.0 dasturlari). Meta-tahlil uchun random-effects model (RevMan 5.4) qo'llanildi, heterogenlik I² indeksi bilan baholandi. Bias baholash: funnel plot va Egger testlari. Etika aspektlari: barcha kiritilgan tadqiqotlar etik standartlarga (Helsinki Deklaratsiyasi) mos, informed consent olingan. Natija va muhokama rhGH davolashi SY bor bolalarda bo'y o'sish dinamikasini sezilarli darajada yaxshilaydi, bu meta-tahlillarda tasdiqlangan. Birinchi yilda HV o'rtacha 9,5-11,5 sm/yilga yetadi (normal 5-7 sm/yil), keyingi yillarda pasayib, 4,5-6,5 sm/yilga tushadi, bu "catch-up growth" fenomenini ko'rsatadi. Yakuniy AH SDS treated guruhda -0,3 (-0,8 dan 0,2), untreatedda -2,1 (-2,8 dan -1,4) bo'lib, treated guruhda yaxshiroq (MD=1,8 SDS, P<0,001). Haftalik LAGH kunlik rhGH bilan taqqoslaganda 12 oyda HV da farq minimal (MD=0,15 sm/yil), ammo 36 oyda ustunlik ko'rsatadi (MD=0,85 sm/yil), chunki compliance yuqori. Metabolik omillar: insulin qarshiligi (HOMA-IR >2,5) ΔHSDS ga salbiy ta'sir qiladi (r=-0,42, P=0,008), FT3 esa ijobiy (r=0,48, P<0,001), hemoglobin va vitamin D esa o'rtacha korrelyatsiya ko'rsatadi. GHD da natijalar ISS ga nisbatan yaxshiroq, HV 624 oylarda 15-25% yuqori (P<0,01). Masalan, tadqiqotlarda boshlang'ich xususiyatlarni ko'rib chiqsak, quyidagi jadvalda keltirilganidek, treated va untreated guruhlar o'rtasida farqlar mavjud: Jadval 1: Tadqiqotlarda boshlang'ich xususiyatlar. Guruh Yosh (yil) Bo'y SDS Peak GH (ng/mL) IGF-1 SDS Bone Age (yil) Treated (n=120) 8,2 ± 2,1 -2,8 ± 0,7 3,5 ± 1,8 -1,9 ± 0,6 6,5 ± 1,9 Untreated (n=95) 8,5 ± 2,3 -2,7 ± 0,6 4,2 ± 2,1 -1,7 ± 0,5 6,8 ± 2,0 Izoh: Ushbu jadval treated va untreated guruhlarning boshlang'ich demografik va klinik ko'rsatkichlarini taqqoslaydi. Treated guruhda peak GH pastroq, bu GHD ni tasdiqlaydi va davolash samarasini bashorat qiladi. Jadval 2: Yakuniy bo'y natijalari. Parametr Treated (o'rtacha ± SD) Untreated (o'rtacha ± SD) MD (95% CI) P qiymati Yakuniy bo'y (sm) 168,2 ± 7,4 162,5 ± 8,1 5,7 (3,2-8,2) <0,001 Yakuniy bo'y SDS -0,3 ± 0,9 -2,1 ± 1,0 1,8 (1,4-2,2) <0,001 Bo'y SDS o'sishi 2,5 ± 0,8 0,6 ± 0,7 1,9 (1,5-2,3) <0,001 Izoh: Jadval yakuniy bo'y parametrlarini taqqoslaydi, treated guruhda sezilarli yaxshilanishni ko'rsatadi. Bu meta-tahlillarda tasdiqlangan, rhGH ning uzoq muddatli samarasini isbotlaydi. Metabolik omillarni tahlil qilganda, quyidagi jadval omillarning korrelyatsiyasini ko'rsatadi: Jadval 3: Metabolik omillar va natijalar. Omil Korrelyatsiya (r) 95% CI P qiymati HOMA-IR -0,42 -0,55 to -0,29 0,008 ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 786 FT3 0,48 0,35 to 0,61 <0,001 Hemoglobin 0,32 0,18 to 0,46 0,015 Vitamin D 0,28 0,12 to 0,44 0,032 Izoh: Jadval metabolik omillarning ΔHSDS bilan bog'lanishini ko'rsatadi. Insulin qarshiligi salbiy ta'sir qiladi, tiroid gormonlari esa ijobiy, bu davolash oldidan skrining zarurligini ta'kidlaydi. Izoh: Ushbu diagramma rhGH davolashining 6 yillik davomida height velocity dinamikasini ko'rsatadi. Birinchi yilda tez o'sish (catch-up), keyin stabilizatsiya kuzatiladi, bu klinik tadqiqotlarda tasdiqlangan tipik egri chiziq. Diagramma 2: rhGH davolashidan keyin height SDS o'sishi. ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 787 Izoh: Diagrammada individual bemorlarda davolashdan oldin va keyin height SDS farqi ko'rsatilgan. O'rtacha o'sish 2,0-2,5 SDS, bu yakuniy bo'yini normalga yaqinlashtiradi. Diagramma 3: rhGH dozasiga bog'liq javob egri chizig'i. Izoh: Ushbu egri chiziq rhGH dozasining height velocity ga ta'sirini ko'rsatadi. Doza oshishi bilan o'sish tezligi ortadi, ammo 0,05 mg/kg dan keyin platoga chiqadi, bu dozani optimallashtirish zarurligini ta'kidlaydi . Rasm 1: rhGH davolashidan oldin va keyin bolalarning surati. ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 788 Izoh: Rasmda bolaning rhGH davolashidan oldin va keyin bo'yi farqi ko'rsatilgan. Davolash o'sishni sezilarli yaxshilagan, bu klinik holatlarda kuzatiladigan vizual misol. Muhokama: Natijalar rhGH ning samaradorligini tasdiqlaydi, ammo individual farqlar (genetika, yosh) muhim. Haftalik usullar qulayroq, ammo IGF-1 monitoring zarur. Nojo'ya ta'sirlar: lokal reaktsiyalar 10-20%, jiddiy hodisalar <1%, ammo uzoq muddatli xavflar (kanserogenez) tadqiqotlarda yo'q. Farmakoekonomika: yillik xarajat 10,000-20,000 USD, ammo QALY (qualityadjusted life years) bo'yicha samarali. Kelajak: gen terapiyasi va yangi agonistlar. Xulosa rhGH SY bor bolalarda bo'y o'sish dinamikasini, metabolik holatni va hayot sifatini yaxshilaydi, birinchi yillarda yuqori HV va yakuniy AH ni ta'minlaydi. Metabolik va genetik omillarni hisobga olish, dozani individualizatsiya qilish va muntazam monitoring muvaffaqiyatni oshiradi. LAGH formulalari qulaylikni oshiradi, ammo kunlik usullar standart bo'lib qolmoqda. Kelajakdagi tadqiqotlar uzoq muddatli xavfsizlik va yangi terapiyalarga qaratilishi kerak. Klinikada rhGH ni erta boshlash va multidiscipline yondashuv tavsiya etiladi. Foydalanilgan adabiyotlar 1. Imperiale, T. F., Speroff, T., Marrero, U., Radcliffe, D. J., & Cuttler, L. (2002). Effect of growth hormone therapy on height in children with idiopathic short stature: A meta-analysis. Archives of Pediatrics & Adolescent Medicine, 156(3), 230–240. https://doi.org/10.1001/archpedi.156.3.230 2. Ranke, M. B. (2021). Short and long-term effects of growth hormone in children and adolescents with GH deficiency. Frontiers in Endocrinology, 12, Article 720419. https://doi.org/10.3389/fendo.2021.720419 3. Kim, J. H., Chae, H. W., Chin, S. O., Ku, C. R., Park, K. H., Lim, D. J., ... & Lee, E. J. (2020). Diagnosis and treatment of growth hormone deficiency: A position statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology. Endocrinology and Metabolism (Seoul), 35(2), 272–287. https://doi.org/10.3803/EnM.2020.35.2.272 4. Tavares, A. B. W., & Collett-Solberg, P. F. (2021). Growth hormone deficiency and the transition from pediatric to adult care. J Pediatr (Rio J), 97(6), 595–602. https://doi.org/10.1016/j.jped.2021.02.007 5. Zhong, X., Chen, Y., Liu, G., Cui, Z., Luo, K., Wu, Z., Xiao, K., & Li, H. (2025). Metabolic factors influencing the efficacy of recombinant human growth hormone therapy in children with short stature. Frontiers in Endocrinology, 16, Article 1691509. https://doi.org/10.3389/fendo.2025.1691509 6. Paltoglou, G., & others. (2020). The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): A systematic review and meta-analysis. Journal of Pediatric Endocrinology and Metabolism, 33(12), 1577–1588. https://doi.org/10.1515/jpem-2020-0287 7. Zhao, Q., Li, R., Shao, Q., Zhang, M., & Ban, B. (2025). Recombinant growth hormone improves growth and adult height: A comparison between treated and untreated patients with idiopathic growth hormone deficiency. Translational Pediatrics, 14(3), 442–451. https://doi.org/10.21037/tp-2024-576 8. Dyrka, K., et al. (2025). Biological effects of recombinant human growth hormone therapy on metabolism in children with growth hormone deficiency: A review. Journal of Pediatric Endocrinology and Metabolism, 38(8), 796-806. https://doi.org/10.1515/jpem-2025-0057 ISSN: 2582-4686 SJIF 2021-3.261, 2022-2.889, 20235.384, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-12 789 9. Zhu, J., et al. (2024). Long-acting growth hormone in the treatment of growth hormone deficiency in children: A systematic literature review and network meta-analysis. Scientific Reports, 14(1), Article 8061. https://doi.org/10.1038/s41598-024-58616-4 10. Ma, Y., et al. (2024). Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view. Medicine (Baltimore), 103(25), e38350. https://doi.org/10.1097/MD.0000000000038350