Efficacy Of Growth Hormone Therapy Research Articles

Acquired neuro-secretory defect in growth hormone secretion due to Imatinib mesylate and the efficacy of growth hormone therapy in children with chronic myeloid leukemia

Imatinib results in growth retardation in children with chronic myeloid leukemia (CML). The study was planned to assess the GHRH-GH-IGF1 axis in children with CML, receiving Imatinib and to evaluate the efficacy of human growth hormone (hGH) therapy. Twenty children with CML, receiving Imatinib for a period exceeding 6 months, with resultant growth retardation were included. The GHRH-GH-IGF1 axis was assessed using growth hormone stimulation tests. IGF-1 generation test was performed for the evaluation of GH insensitivity. The mean age at inclusion was 15.2 years. The mean duration of treatment with Imatinib was 5.7 years. The mean decrease in height SDS since the start of Imatinib was −0.95 (p = 0.008). IGF-1 SDS was <-2 in all the patients. 71.4% of patients had a suboptimal GH response following stimulation with GHRH-Arginine. All patients had stimulable, although a delayed GH response with glucagon stimulation. 20% of patients had GH insensitivity. Four patients were treated with hGH for a mean duration of 5.75 months, achieved normalization of IGF-1 levels and improvement in growth velocity improved from 0.21 to 0.86 cm/month. Imatinib results in an acquired neurosecretory defect in GH secretion. Treatment with growth hormone leads to an improvement in growth velocity and normalization of IGF-1.

Evaluation of Safety and Efficacy of Growth Hormone Therapy by IGF-1 Z Score in Children with Short Stature.

This study aims to explore the safety and efficacy of growth hormone (GH) therapy by retrospectively analyzing the changes of insulin-like growth factor-1 (IGF-1) Z-scores in children with short stature after treatment with GH. The etiology of 104 children with short stature was classified according to the GH stimulation test and IGF-1 levels: (1) growth hormone deficiency (GHD); (2) mild growth hormone deficiency (M-GHD); (3) idiopathic short stature (ISS); (4) GH insensitivity syndrome (GHIS). In addition, all patients were treated with recombinant human growth hormone (rhGH) for 12months, and the growth rate (Gv), height, body mass, bone age, height standard deviation scores (HtSDS), IGF-1 and adverse reactions were compared among these three groups before and after treatment. The height, body mass, Gv and HtSDS were significantly higher in each group compared with those before treatment. Furthermore, the Z-score of IGF-1 significantly increased after 1month of GH treatment and was positively correlated with the dosage of GH. Moreover, the difference in standard deviation score was significantly positively correlated with the increase in standard deviation score of IGF-1. The detection of the GH-IGF-1 axis function can be carried out for the etiologic diagnosis of short stature. IGF-1 increased after rhGH treatment, and IGF-1 level was correlated to the time of therapy and dosage of GH. IGF-1-based GH dosing targeted to age- and gender-adjusted means may save medical costs and offer a more dose-sparing and potentially safer mode of therapy compared with traditional weight-based dosing.

Novel mutation of type-1 insulin-like growth factor receptor (IGF-1R) gene in a severe short stature pedigree identified by targeted next-generation sequencing

Insulin-like growth factor receptor (IGF-1R) deficiency is a rare form of short stature, and is difficult to clinically diagnose. Targeted next-generation sequencing (NGS) allows for the rapid and inexpensive assessment of short stature. We identified mutations in the pedigree of a Chinese boy with severe short stature using targeted NGS; we then assessed the clinical characteristicsand evaluated the efficacy of growth hormone therapy. NGS analysis revealed a novel heterozygous missense mutation in exon3 (c.926C>T, p.S309L) of the type-I IGF-1R gene in the proband, which was inherited from the mother. The proband, mother and grandfather suffered from severe growth failure. After recombinant human growth hormone therapy, the patient's growth rate increased. The novel missensemutation in IGF-1R (c.926C > T, p.S309L) is associated with severe short stature in Chinese individuals. Targeted NGS may enable efficient diagnosis and genetic consultation of children with short stature.

A Critical Appraisal of Growth Hormone Therapy in Growth Hormone Deficiency and Turner Syndrome Patients in Turkey.

Early detection of abnormal growth, identification of the underlying cause, and appropriate treatment of the medical condition is an important issue for children with short stature. Growth hormone (GH) therapy is widely used in GH-deficient children and also in non-GH-deficient short stature cases who have findings conforming to certain indications. Efficacy of GH therapy has been shown in a multitude of short- and long-term studies. Age at onset of GH therapy is the most important factor for a successful treatment outcome. Optimal dosing is also essential. The aim of this review was to focus on challenges in the early diagnosis and appropriate management of short stature due to GH deficiency (GHD) and Turner syndrome. These are the most frequent two indications for GH therapy in Turkey approved by the Ministry of Health for coverage by the national insurance system.

Efficacy of growth hormone therapy in Kearns-Sayre syndrome: the KIGS experience.

Kearns-Sayre syndrome (KSS) is characterized by external ophthalmoplegia, retinal pigmentation and cardiac conduction defects due to mitochondrial DNA (mtDNA) deletions. Short stature and growth hormone (GH) deficiency have been reported in KSS, but data on GH treatment is limited. We describe the clinical presentation, phenotype evolution, and response to GH in a patient with KSS and report data on eight additional KSS patients from the KIGS database. Our patient with KSS and GH deficiency achieved a final adult height at -0.8 SDS. In the KIGS database GH treatment resulted in mean improvement in height from -3.9 to -2.9 SDS in patients with KSS. Two patients did not show growth improvement. Our data shows improvement in height SDS in our patient and mixed results in eight additional patients from the KIGS database after treatment with GH. Heterogeneity in responsiveness may relate to presence of GH deficiency or severity of underlying mitochondrial dysfunction.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19.

Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency.

PurposeGrowth hormone (GH) plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD). This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters.MethodsA total of 45 patients (17 females and 28 males) diagnosed with childhood-onset GHD (CO-GHD) were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4±5.0 years (18.0-32.1 years). Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI), serum insulin-like growth factor 1 (IGF-1), serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed.ResultsOf 45 patients, 33 patients had GH interruption period of 4.3±3.6 years (0.7-12.5 years). Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters.ConclusionBMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.

Biological markers of tissue-specific effects of GH therapy

Different genes are potentially activated in lean and adipose tissue in response to recombinant human growth hormone (GH) or its mediator, insulin-like growth factor 1. Decker and colleagues now present evidence that levels of circulating protein markers give clues about the biological efficacy of GH therapy in various body tissue compartments.

Systematic Review: The Safety and Efficacy of Growth Hormone in the Healthy Elderly

Human growth hormone (GH) is widely used as an antiaging therapy, although its use for this purpose has not been approved by the U.S. Food and Drug Administration and its distribution as an antiaging agent is illegal in the United States. To evaluate the safety and efficacy of GH therapy in the healthy elderly. The authors searched MEDLINE and EMBASE databases for English-language studies published through 21 November 2005 by using such terms as growth hormone and aging. The authors included randomized, controlled trials that compared GH therapy with no GH therapy or GH and lifestyle interventions (exercise with or without diet) with lifestyle interventions alone. Included trials provided GH for 2 weeks or more to community-dwelling participants with a mean age of 50 years or more and a body mass index of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment for a specific illness. Two authors independently reviewed articles and abstracted data. 31 articles describing 18 unique study populations met the inclusion criteria. A total of 220 participants who received GH (107 person-years) completed their respective studies. Study participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly after adjustment for body composition changes. Other outcomes, including bone density and other serum lipid levels, did not change. Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose. Some important outcomes were infrequently or heterogeneously measured and could not be synthesized. Most included studies had small sample sizes. The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

Growth hormone level during stimulation test and efficacy of growth hormone therapy of idiopathically undersized children with this hormone insufficiency

For the first time, a broad study of the effectiveness of treatment with growth hormone (GH) in patients with varying degrees of impaired secretion of GH is undertaken. In this work, 885 patients of pre-pubertal age who received treatment for 1 year were examined. All children were given 2 standard tests with stimulation of the secretion of GH. The following diagnoses were established: idiopathic insufficiency of GH (classification number 1.1) or idiopathic stunting (3.1). Patients were divided into groups depending on the maximum release of GH during sampling: A - in both samples 5 ng/ml, B - in one sample 5 ng/ml, in another - 5-10 ng/ml, C - in both samples 5-10 ng/ml, D - in one sample 5-10 ng/ml, in another - 10 ng/ml, E - in both samples 10 ng/ml.anthropometric indicators, main parameters of therapy and results of treatment of GY were evaluated in all developed model (expected RESULTS). According to the study, patients with the most severe GH deficiency (group A) had better treatment outcomes, while the other groups were almost identical. The division of group A into a subgroup with isolated GH deficiency and a subgroup with deficiency of other tropic hormones (hypopituitarism) showed that in the first subgroup the growth of parents was significantly lower. Thus, despite the fact that standard samples with stimulation of GH can be used to diagnose the insufficiency of GH, the results of these samples do not always allow to predict the effectiveness of treatment of GH for 1 year. It should also be noted that the shortness of the parents, especially the growth of the mother, may indicate the presence of an additional hereditary factor in the Genesis of shortness in these patients.

Turner syndrome: A fresh look

Introduction of improved therapy for a disease often prompts a closer look and results in revision of previous concepts. The availability of biosynthetic human growth hormone (GH) has stimulated interest in a variety of growth disorders. There are two particularly important areas for clinical investigation: More complete information is needed as to which disorders respond to GH and what are the long-term beneficial and adverse effects. It is no less important to enhance our understanding of the psychological effects of short stature and its treatment. The ultimate goal of GH treatment is not to make the child taller, but to improve his or her well-being in the critical areas of family, school, and social life. It follows then that the efficacy of GH therapy cannot be evaluated by auxological measures alone. It is necessary to have a far better understanding than we now have of the impact of short stature on well-being in childhood and adult life. Biological parameters such as height do not affect the person in a direct way, but interact in a complex way to affect quality of life. It is particularly important to develop a better understanding of the effect of improving height in children with multiple anomalies or handicaps. Such children make up a large proportion of those followed in pediatric subspecialty clinics. The large-scale studies that are in progress should considerably enhance our knowledge of these important matters. The proceedings of the Turner symposium presented here are a valuable contribution toward a comprehensive understanding of one such syndrome comprised of multiple abnormalities. It represents a unique