Treatment Of Idiopathic Short Stature Research Articles

Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial.

Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Open-label trial with 2 treatment arms. Pediatric Endocrine Clinic at Stanford. A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.

Comparative effectiveness of East Asian traditional medicine for treatment of idiopathic short stature in children: systematic review and network meta-analysis

Brief Summary: This systematic review found that East Asian traditional medicine (EATM) therapies may have beneficial effects in children with idiopathic short stature, however, high-quality studies are necessary.

A Real-World Study of Recombinant Human Growth Hormone in the Treatment of Idiopathic Short Stature and Growth Hormone Deficiency.

ObjectiveThis study aimed to evaluate the clinical efficacy of recombinant human growth hormone (rhGH) in the treatment of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) and to explore the related factors affecting treatment efficacy.MethodsThe current research reflects a real-world study. A total of 79 patients with ISS and 95 patients with GHD (both groups pre-puberty) who had been treated with rhGH for more than one year from January 2010 to September 2019 were included in this study. The patients were divided into two groups, ie, an ISS and a GHD group, respectively. The growth indexes, such as chronological age (CA), bone age (BA), height standard deviation score (HtSDS), insulin-like growth factor-1 (IGF-1) SDS, and body mass index were recorded and compared between the two groups before and after treatment. The treatment efficacy was evaluated according to changes in HtSDS before and after treatment, and the influencing factors of clinical efficacy were analyzed using a multivariate regression model.ResultsAt the start of treatment, the differences in CA, BA, height, weight, sexual development stage, HtSDS, mid-parental height SDS, and IGF-1 SDS between the two groups were not statistically significant (P > 0.05). However, the initial dose of rhGH in the GHD group was significantly lower than in the ISS group (P < 0.001). Following rhGH treatment, the differences in CA, BA, BA/CA ratio, and IGF-1 SDS measured at 6, 12, 18, and 24 months between the ISS and GHD groups were not statistically significant, while the difference in HtSDS measured at 6 months was statistically significant. With the extension of rhGH treatment time, the annual growth rate (GV) gradually decreased, and the difference between HtSDS and the baseline gradually increased; however, the differences between the ISS and GHD groups were not statistically significant. The most important factor affecting the treatment efficacy for patients with ISS was age at the start of treatment; the most important factors affecting the treatment efficacy for patients with GHD were age and IGF-1 SDS.ConclusionRecombinant human growth hormone treatment can significantly improve the height of patients with ISS and GHD. There was no significant difference in growth rate between patients with ISS and those with GHD at relatively high doses. The common factor affecting the treatment efficacy of the two groups was the age at the start of treatment. During treatment, monitored data indicated that rhGH treatment of GHD and ISS thyroid function showed a clinical phenomenon in the form of increased free triiodothyronine, rather than hypothyroidism, which was rarely reported in existing studies.

POSC303 Comparative Effectiveness of Integrative Medicine for Treatment of Idiopathic Short Stature in Children: A Systematic Review and Network Meta-Analysis

Idiopathic short stature (ISS) is a common problem in children and causes many economic and social burdens. These days, integrative medicine therapies are widely used for children with ISS. In this study, we compared and ranked various integrative therapies for the treatment of pediatric ISS using network meta-analysis (NMA).

Comparative effectiveness of East Asian traditional medicine for treatment of idiopathic short stature in children: A protocol for systematic review and network meta-analysis.

Background:There are many East Asian traditional medicine (EATM) therapies that are widely used and effective for idiopathic short stature (ISS) in children. However, the comparative effectiveness of these therapies remains unclear. We describe the methods that will be used to comparatively evaluate the efficacy and safety of EATM therapies for the treatment of pediatric ISS.Methods and analysis:Fourteen electronic English, Korean, Chinese, and Japanese databases will be searched up to August 2020 for relevant randomized controlled trials of various EATMs for the treatment of pediatric ISS, without language or publication status restrictions. The primary outcome will be growth-related anthropometric indicators, and acceptability, measured through drop-outs that occur during treatment for any reason. We will conduct a pairwise meta-analysis for direct comparisons if multiple studies use the same types of intervention, comparison, and outcome measure. A frequentist network meta-analysis will be performed to summarize the available direct and indirect evidence regarding various EATM options for pediatric ISS. The risk of bias for the included studies will be evaluated using the Cochrane Collaboration's risk of bias tool.Conclusions:The findings of this review will provide evidence for the comparative effectiveness and ranks of current EATMs and help to inform clinical practitioners, patients, and policy makers in decision making.Ethics and dissemination:Ethical approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through a peer-reviewed publication or conference presentations.Protocol registration number:OSF (URL: https://osf.io/s4vp7), PROSPERO CRD42020187160

Concerns and Expectations of Parents Seeking Subspecialist Care for Their Child’s Short Stature

Introduction: Parents (PP) of children in primary care clinics previously reported factors influencing their height-related medical decision making. However, patients seeking height-related care in endocrine subspecialty clinics and their parents (EP) differ demographically from the general population. Objective: To determine EP height-related medical concerns and expectations, and to compare between EP and PP. Methods: EP completed a survey assessing their concerns in seeking medical care for their child’s height with identical questions previously asked of PP and two additional questions about growth hormone (GH) treatment. Results: A greater proportion of the 166 EP (80% response rate) than the 1,820 PP (83% response rate) previously surveyed was Caucasian (75% EP, 41% PP) and privately insured (80% EP, 58% PP). Both groups rated treatment efficacy and risks most as having a bigor extreme impact on decision making (65% EP, 58% PP). The second most rated concern for EP was comparison of child’s height to peers or growth chart (60% EP, 32% PP) versus child’s health for PP (54% EP, 56% PP). Of the 166 EP surveyed, 76% rated GH treatment as potentially improving quality of life (QoL), with 88% reporting a minimum 3-inch height increase as necessary to improve QoL. Conclusions: Height comparisons were more likely to impact EP than PP in seeking height-related medical care for their children. EP had high expectations of QoL improvement with GH treatment, which are unlikely to be met with treatment of idiopathic short stature. Thus, clinicians should be prepared to support families in other ways that promote positive development in children with short stature.

US Growth Hormone Use in the Idiopathic Short Stature Era: Trends in Insurer Payments and Patient Financial Burden.

ObjectiveTo investigate trends in prevalence and expenditures of growth hormone (GH) use by US youth in the last 15 years, a period during which the US Food and Drug Administration (FDA) approved GH treatment of idiopathic short stature (ISS), and insurers imposed greater barriers to GH treatment reimbursements.DesignWith the use of 2001 to 2016 OptumInsight commercial claims data, we analyzed trends in claims of GH drugs among beneficiaries aged 0 to 18 years (n = 38,857 beneficiaries receiving GH). Outcome measures included annual prevalence of GH claims and annual total insurer and total patient payments for GH claims. t Tests were used for linear time trends in outcomes. The percentage of beneficiaries switching GH brands also was calculated.ResultsThe number of members with GH claims per 10,000 beneficiaries under age 18 rose steadily from 5.1 in 2001 to 14.6 in 2016, without a dramatic change around 2003, the ISS approval date. Mean total GH expenditures decreased (−26% in constant dollars), as did the estimated insurance paid amount (−28%). However, mean total patient spending increased by 163%. Beneficiaries switching GH brands in the year ranged from 1.4% to 3.6% in 2001 to 2007 and from 5.1% to 8.8% after, with 25.6% switching in 2009 and 13.9% switching in 2015.ConclusionsThe FDA ISS approval was not a watershed event in the steady increase in GH use by US youth. Progressive restrictions on coverage and formulary preference coverage strategies appear to have succeeded in lowering total expenditures and insurer burden of GH treatment per beneficiary. However, those savings were not passed on to patients who bore greater burdens financially and from brand switches.

Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.

Efficacy and safety of recombinant human growth hormone in treating Chinese children with idiopathic short stature

ObjectiveThis study aims to investigate the efficacy and safety of recombinant human growth hormone (rhGH) in the treatment of idiopathic short stature (ISS). MethodsThe data of 200 ISS children, who were treated with rhGH from January 2008 to December 2016, were collected and retrospectively analyzed. The data of height, bone age(BA), chronological age(CA), fasting blood glucose, fasting insulin, thyroid function and IGF-1 were collected, and annual growth velocity (GV), height standard deviation score (HtSDS) and related factors that affect GV were statistically analyzed. Results(1) GV and HtSDS changes: As the time of treatment increased, the GV decreased year by year. The GV in the second year was significantly lower than that in the first year (P < .0001), and the GV in the fourth year was significantly lower than that in the third year (P < .05). HtSDS gradually increased from the first year to the third year, and became significantly higher than that in the year before the treatment (P < .01). The difference in the increase in HtSDS between the fourth year and third year was not statistically significant (P > .05). (2) The influence factors of GV included age at initial treatment, IGF-1SDS during treatment and GV in the year before treatment. (3) The most common side effects during treatment included transient hyperglycemia and temporary hyperinsulinemia, and these returned to normal after the treatment was stopped. Some patients presented with accelerated bone age growth after two years of treatment (annual growth of bone age △BA was >2 years), compared with children without accelerated bone age growth, and the difference between BA and CA (BA-CA) was significantly reduced at the beginning of the treatment (P < .01). ConclusionrhGH has a good growth promoting effect on ISS children. A variety of factors may affect the GV, and related adverse reactions should be monitored during the treatment.

Актуальні питання діагностики і лікування ідіопатичної низькорослості в дітей

Актуальні питання діагностики і лікування ідіопатичної низькорослості в дітей

Gender Bias in U.S. Pediatric Growth Hormone Treatment

Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <−2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <−2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5–20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <−2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <−2.25 SD. No gender differences in prevalence of height <−2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <−2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

Growth hormone, enhancement and the pharmaceuticalisation of short stature

This paper takes the biological drug human Growth Hormone (hGH) as a case study to investigate processes of pharmaceuticalisation and medicalisation in configuring childhood short stature as a site for pharmaceutical intervention. Human growth hormone is considered to have legitimate applications in treating childhood growth hormone deficiency and short stature associated with other recognised conditions. It is also regarded by bioethicists and others as a form of human biomedical enhancement when applied to children with idiopathic or ‘normal’ short stature. The purpose of this study is not to evaluate whether treatment of idiopathic short stature is enhancement or not, but to evaluate how some applications of hGH in treating short stature have come to be accepted and stabilised as legitimate ‘therapies’ while others remain contested as ‘enhancements’. A comparative, historical approach is employed, drawing on approaches from medical sociology and Science and Technology Studies (STS) to set out a socio-technical history of hGH in the US and UK. Through this history the relative influence and interplay of drivers of pharmaceuticalisation, including industry marketing and networks of drug distribution, and processes of medicalisation will be employed to address this question and simultaneously query the value of enhancement as a sociological concept.

Debate: Idiopathic short stature should be treated with growth hormone

In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with 'idiopathic' short stature are not 'short, normal children' and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost-effective in idiopathic short-stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment.

Classification, diagnosis, and treatment of idiopathic short stature

Idiopathic short stature is the low stature in which all possible causes are excluded. The diagnosis and treatment of idiopathic short stature are the subject of constant controversy and discussion. With the expansion of indications for growth hormone therapy for conditions unaccompanied by growth hormone deficiency, there has been recently a challenge as to its use in idiopathic short stature. To date, there has been much worldwide evidence for the efficiency and safety of growth hormone therapy in children with idiopathic short stature. In 2008, the International consensus on the diagnosis and management of idiopathic short stature, prepared through the joint collaboration of three research societies: the Growth Hormone Society, the Lowson Wilkins Society of Pediatric Endocrinology (USA), and the European Society of Pediatric Endocrinology. The main points of this document have formed the basis for this paper.

Controversies in the Definition and Treatment of Idiopathic Short Stature (ISS)

The term idiopathic short stature (ISS) refers to short children with no identifiable disorder of the growth hormone (GH)/insulin like growth factor (IGF) axis and no other endocrine, genetic or organ system disorder. This heterogeneous group of short children without GH deficiency (GHD) includes children with constitutional delay of growth and puberty, familial short stature, or both, as well as those with subtle cartilage and bone dysplasias. In rare cases, ISS is due to IGF molecular abnormalities. In this review we tackle the major challenges in the definition and treatment of ISS.Conflict of interest:None declared.

Mecasermin (recombinant human insulin-like growth factor I)

Growth hormone (GH) exercises its growth effects by stimulating insulin-like growth factor I (IGF-I) synthesis in the liver (endocrine IGF-I) and by inducing chondrocyte differentiation/replication and local production of IGF-I (paracrine/autocrine IGF-I). Injectable recombinant human (rh)IGF-I (mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an insulin-sensitizing agent in severe insulin-resistant conditions. Although the insulin-sensitizing effect may benefit both type 1 and type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of IGF-I and include chronic liver disease, cystic fibrosis, wound healing, AIDS muscle wasting, burns, osteoporosis, Crohn's disease, anorexia nervosa, Werner syndrome, X-linked severe combined immunodeficiency, Alzheimer's disease, muscular dystrophy, amyotrophic lateral sclerosis, hearing loss prevention, spinal cord injury, cardiovascular protection, and prevention of retinopathy of prematurity. The most frequent side effect is hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve hyperplasia of lymphoid tissue, which may require tonsillectomy/adenoidectomy, accumulation of body fat, and coarsening of facies. The anti-apoptotic properties of IGF-I are implicated in cancer pathogenesis-a concern for long-term therapy. It is unlikely that mecasermin will be useful beyond the orphan indications of severe insulin resistance and GH insensitivity.

Ethical Considerations: Growth Hormone Treatment in Children with Idiopathic Short Stature

Being short is a natural diversity of the human race. In 2003, the Food and Drug Administration (FDA) approved the use of growth hormone (GH) for the treatment of idiopathic short stature (ISS) in children. Research has shown that GH therapy in children with ISS has a variable effect on increasing height. However, the literature has not shown the efficacy in improving psychosocial function to justify the costs and potential adverse effects. GH use in children with ISS is a subject of great ethical debate. Ethical implications including beneficence, nonmaleficence, autonomy, and justice are discussed. ISS requires thoughtful consideration by the patient, parents, and healthcare professionals. Well-designed long-term studies are needed to determine the benefits of such treatment.

Is there a role for recombinant insulin-like growth factor-I in the treatment of idiopathic short stature?

Recombinant human insulin-like growth factor-I (rhIGF-I) has been used during the past decade for the treatment of severe IGF-I deficiency resulting from growth-hormone receptor deficiency (Laron syndrome), and for growth-hormone gene deletion in which inactivating antibodies to exogenous recombinant human growth hormone have developed. In total, about 150 patients have been treated with rhIGF-I for these conditions.1–5 Data for 61 of these patients were used for US Food and Drug Administration approval of rhIGF-I (mecasermin; Increlex, Tercica, Brisbane, CA, USA) and data for another 25 patients in approval of the binary protein complex of rhIGF-I and IGF-I binding protein-3 (mecasermin rinfabate; iPlex, Insmed, Glen Allen, VA, USA), as orphan drugs.

Long-Term Growth Hormone Treatment of Idiopathic Short Stature

Long-Term Growth Hormone Treatment of Idiopathic Short Stature

Efficacy and Safety Results of Long-term Growth Hormone Treatment of Idiopathic Short Stature

Efficacy and Safety Results of Long-term Growth Hormone Treatment of Idiopathic Short Stature