Idiopathic short stature (ISS) is the most common type of growth retardation (dwarfism) in children, which refers to the short stature of proportionality for which the etiology is not yet clear. It is the most common type of growth retardation (dwarfism) in children. Its height is lower than 2 standard deviations (SD) or the 3rd percentile of the mean value of children of the same age and sex, the growth velocity (GV) is slow, but the birth weight and length reach the normal range, and the peak value of blood growth hormone (GH) excitation is more than 10 μg/L, and growth hormone deficiency (GHD), other endocrine, genetic-metabolic diseases, and other diseases such as diabetes, diabetes mellitus, and other diseases such as diabetes mellitus are ruled out in clinic. In the clinic, growth hormone deficiency (GHD), other endocrine, genetic and metabolic diseases, malnutrition and chronic diseases were ruled out as causes of growth retardation. Replacement therapy with recombinant human growth hormone (rhGH) In July 2003, the U.S. Food and Drug Administration (FDA) approved the use of rhGH for the treatment of ISS, which is the fifth indication approved by the FDA for short stature that is not caused by GHD, following Turner syndrome, Prader-Willi syndrome (PWS), chronic renal insufficiency, and small for gestational age (SGA). Short stature is an indication for non-GHD short stature. The efficacy of rhGH is related to the age of treatment, bone age, dose and duration of treatment, as well as the sensitivity of the individual to rhGH. (1) Effectiveness Most of the clinical studies have shown that although there is no GH deficiency in children with ISS, treatment with rhGH can help to increase the GV and final adult height (FAH) of children with ISS. There is also a clear dose-dependence, i.e., the efficacy of large doses is better than that of small doses. (2) Safety Since the emergence of rhGH, there has been a history of nearly 30 years, and its clinical application has been increasing, because the endocrine axis of GH-IGF-I (insulin-like growth factor-I) plays an important role in the regulation of cell growth and anti-apoptosis, which has aroused the clinical concern about the safety of rhGH application. rhGH is used in the treatment of ISS, and there are very few reports of the adverse reactions, and rarely cause discontinuation of medication. Adverse effects of rhGH in ISS treatment have been rarely reported, and very few have led to discontinuation of the drug, most of which are due to the children’s fear of needles. Many clinical trials have examined the theoretical risks of rhGH (e.g., glucose tolerance, hypertension, cardiovascular changes, triglyceride and cholesterol changes, hypothyroidism, idiopathic benign elevation of cranial pressure, leukemia, and other malignant tumors), and have found no major adverse effects. Kemp et al. reported on a safety analysis of 8018 children with ISS treated with rhGH by the North American National Growth Study Cooperative (NCGS), which did not reveal any new adverse events, and some of the more serious adverse events observed (e.g., burkitt’s lymphoma, type 1 diabetes mellitus, and seizure-like convulsions) were not significantly increased in relation to the prevalence of the disease in the general population. It is worth noting that, although rhGH treatment is generally safe, the indications for treatment should be strictly controlled, and should be used with caution in children with a family history of cancer, history of tumors, history of radiation and chemotherapy, aplastic anemia, Down syndrome, Lonhans histiocytosis and other risk factors for cancer, and to monitor the level of IGF-I/IGFBP3, and adjust the treatment regimen in time for those with a significant increase in IGF-I. For children with significant increase in IGF-I, the treatment program should be adjusted in time. (3) Dosage The effective booster dose of ISS should be 0.15-0.2IU/(kg・d), similar to Turner syndrome. In other previous indications of rhGH, it has been proved that the efficacy of large dose of growth-enhancing drugs is better than that of small dose, especially for children entering pubertal development, it should be mimicked the physiological increase of GH secretion in the growth acceleration of puberty and adopt the treatment of larger dose. Recently, a prospective study on rhGH treatment for children with ISS was reported, aiming at observing the relationship between the degree of improvement of FAH and the therapeutic dose. Recently, studies have proposed that the therapeutic dose of rhGH should be based on the principle of individualization, and put forward the evaluation and measurement methods of the therapeutic dose and efficacy of rhGH. rhGH’s individualized therapeutic strategy should at least consider the following two aspects: the bioavailability of the drug in vivo; the sensitivity of the organism’s response to rhGH. The biological effect of human GH is to promote the synthesis of IGF-I, and it has been found that the boosting therapeutic effect of exogenous GH is correlated with the level of IGF-I in a positive manner. It has been found that the efficacy of exogenous GH is positively correlated with the level of IGF-I. The effectiveness of rhGH treatment can be initially judged by monitoring the level of IGF-I in the peripheral blood, and combined with the change of GV after treatment, which can be used as the basis of adjusting the dose of the drug. This kind of individualized medication may be more helpful to bring out the beneficial effects of the drug and reduce the adverse effects. Many clinical studies have demonstrated that the majority of ISS can be effectively treated with standardized individualized rhGH therapy. Clinicians should provide each child with an individualized treatment plan that is both effective and free of significant adverse effects. (4) Frequency of injections In previous clinical practice, rhGH therapy for both GHD and non-GHD children was shown to be more effective when injected every night before bedtime, so most children are still treated with daily injections. (5) Duration of therapy There is a relatively consistent understanding of the association between the duration of rhGH therapy and its efficacy in children with ISS. The first year of therapy shows the most pronounced increase in GV and HtSDS, and the growth-promoting effect may tend to diminish in the subsequent years. Nevertheless, the GV of prepubertal ISS children after a long course of treatment (up to 7 years) is still greater than the pre-treatment level. This confirms that rhGH treatment in children with ISS leads to a sustained increase in GV, i.e., a short course of treatment increases GV, and a long course of treatment contributes to an increase in FAH. (6) Factors affecting efficacy Factors affecting the efficacy of ISS in growth promotion (especially the positive effect on FAH) are generally the same as those for GHD, and they include basal body height (BH) at the start of treatment, GV, age at birth (BA), age of initiation of puberty, age of onset of puberty, GV at the first year of treatment, and the age of onset of pubertal sexual development (GV at the beginning of treatment). These include basal height at the start of treatment, GV, bone age (BA), onset of pubertal sex development, GV in the first year of treatment, duration of treatment, inherited height, and birth length. The younger the actual age at the start of treatment, the more pronounced the delay in BA, the lower the GV and blood IGF-I levels, and the better the genetic height, the better the outcome. The more significant the increase in GV during the first year of treatment, the greater the likelihood that FAH will be beneficial; on the other hand, if there is no significant increase in GV during the first year of treatment, discontinuation of the drug may be considered. In conclusion, replacement therapy with recombinant human growth hormone rhGH in children with ISS can effectively improve the annual growth rate and increase lifetime height, and the long-term use of the drug is safe and effective without serious side effects.The increase in lifetime height of children with ISS is correlated with the age of initiation of the drug and the duration of the drug, and it is in a dose-dependent manner.