Comparison between the growth response to growth hormone (GH) therapy in children with partial GH insensitivity or mild GH deficiency / Comparação entre a resposta de crescimento ao tratamento com hormônio de crescimento (GH) em crianças com insensibilidade parcial ao GH ou deficiência de GH leve

Objectives: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD.Subjects and methods: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1 st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS).Results: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD.Conclusion: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.

Objetivos: O tratamento com GH é ainda controverso, salvo na deficiência grave de GH (SGHD). O objetivo deste estudo foi comparar a resposta ao tratamento com GH em indivíduos com insensibilidade parcial ao GH (PGHIS) e na deficiência moderada do GH (MGHD) com SGHD.Sujeitos e métodos: Quinze pacientes com PGHIS, 11 com MGHD e 19 com SGHD, seguidos por mais de um ano no Sistema Único de Saúde, foram avaliados antropométrica e laboratorialmente, no início, com um ano de tratamento e na última avaliação (tempo máximo de dez anos na SGHD, quatro anos na MGHD e oito anos na PGHIS).Resultados: O escore de desvio-padrão (EDP) da estatura inicial foi menor nos indivíduos com SGHD do que naqueles com MGHD e PGHIS. Embora o aumento no EDP da estatura no primeiro ano em comparação com o inicial não fosse diferente entre os grupos, o EDP da altura no primeiro ano de tratamento permaneceu menor na SGHD que na MGHD. Não houve diferença no EDP da estatura na última avaliação entre os três grupos. O tratamento com GH, no período completo da observação, provocou uma tendência a menor aumento no EDP da estatura nos pacientes com PGHIS que naqueles com SGHD, entretanto aumentos semelhantes foram encontrados nos grupos MGHD e SGHD.Conclusão: O tratamento com GH aumentou a estatura nos indivíduos com PGHIS e produziu efeitos similares na estatura em MGHD e SGHD.

Children with isolated growth hormone deficiency: Empty sella versus normal sella.

BACKGROUND: Empty sella (ES) may be associated with variable clinical conditions ranging from the occasional discovery of a clinically asymptomatic pouch within the sella turcica to severe intracranial hypertension and rhinorrhea. The need for replacement hormone therapy in ES, as in other syndromes that may cause hypopituitarism, must be assessed for every single hormone, including growth hormone (GH). AIM: To determine whether or not the presence of ES could allow some changes in the GH responses of the isolated growth hormone deficiency (GHD) patients. MATERIALS AND METHODS: We included a cohort of 59 short stature children and adolescents with isolated GHD. According to computed tomography finding, they were classified into 2 groups: Group 1 included 40 children with normal sella and 19 children with ES in Group 2. All patients received recombinant human growth hormone (rhGH) with a standard dose of 20 IU/m2/week. RESULTS: The baseline results were not significantly different for all variables except weight standard deviation was smaller with statistical significant difference (P = 0.02). We identified no significant differences when comparing both groups, except for height standard deviation (HTSD) after the first year of therapy which revealed significant difference in favor of group 1. When comparing pre- and the two post-treatments HTSD results of the studied cases, all showed significant changes after GH therapy. The results of related variables pre-and post-treatment in both the groups showed significant improvement in all variables of the two groups of the study. CONCLUSION: Our study showed a similar stature outcome in the two treatment groups.

Bone age is the best predictor of growth response to recombinant human growth hormone in Turner’s syndrome.

BACKGROUND AND OBJECTIVES: Recombinant human growth hormone (rhGH) is approved for use in children with Turner’s syndrome (TS) in most industrialized countries and is recommended in the recently issued guidelines. We determined the growth responses of girls who are treated with rhGH for TS, with an aim to identify the predictors of growth response. MATERIALS AND METHODS: Fifty-six prepubertal girls with TS, documented by peripheral blood karyotype, were enrolled. All the patients received biosynthetic growth hormone therapy with a standard dose of 30 IU/m2/week. The calculated dose per week was divided for 6 days and given subcutaneously at night. RESULTS: This study showed that rhGH therapy provides satisfactory auxological results. Bone age delay is to be considered as a predictive factor which may negatively influence the effect of rhGH therapy on final height. The growth velocity in the preceding year is the most important predictor of rhGH therapy response. CONCLUSION: These observations help us to guide rhGH prescription, to reduce the risks and costs.

Talla baja idiopática y uso de hormona de crecimiento: documento del consenso de la Sociedad Chilena de Endocrinología y Diabetes / Consensus recommendations of the Chilean Society of Endocrinology an Diabetes on growth hormone use in idiopathic short stature

The diagnosis of idiopathic short stature (ISS) is common among patients with short stature, especially those with a height lower than 2 standard deviations (SD) of the mean. The diagnosis of ISS is considered in children with short stature in whom no recognizable causes are found after a proper evaluation by pediatric endocrinologists. The professional must perform a complete personal and family history, appropriate anthropometry and physical examination and confirm that general and specific laboratory studies including supraphysiological stimuli to measure growth hormone, are normal. Growth hormone (GH) treatment is safe and effective in patients with ISS. Its effects are very similar to those observed in other conditions that affect growth as Turner Syndrome and Small for Gestational Age Short Children. However, treatment is still controversial because ethical, psychological, social, cultural and economic issues, wich are difficult to evaluate, must be taken into account. Individual patient differences and their family environment must also be considered. The hormone is more often indicated to fulfil parent or social environment needs rather than the wish of the patients. Although the treatment is safe, it is not free of complications and its results are often poorer than those expected by patients or their parents. The Chilean Society of Endocrinology and diabetes commissioned a panel of experts among its members, to generate a consensus document on ISS and the use of growth hormone, to provide information and recommendations to the Chilean community.

Response to growth hormone therapy in indian patients.

Objective. To analyse response to growth hormone therapy on Indian patients with short stature. Methods. Data were collected on 71 patients of short stature on GHT. All patients underwent clinical and hormonal evaluation. GHD was diagnosed in the presence of short stature (height SDS < 2) and peak GH levels < 10 ng/ml. Bone age was estimated using Tanner Whitehouse 3 method (TW3). Results. Primary GHD (73%) was the commonest diagnosis among patients on GHT, followed by organic GHD (12.6%), genetic syndromes (8.4%) and systemic diseases (5.4%). Mean chronological age at presentation was 10.07±3.26 years (median-11 years, range 3-15 years), mean height age was 6.98±2.82 years (median 7.5 years, range 1-13 years) and mean bone age (available for 55 patients) was 7.19±3.1 years (median 8.2 years, range 1.3 - 13 years). Patients with systemic diseases (6.75±3.5 years) presented earlier, compared to patients with GHD (10.27±3.16 years) and genetic syndromes (10.18±3.20 years) (p=0.349). Most of the patients on GHT were in the age group 9-15 years (60.6%). Mean height gain with GHT was 8.7±2.7 cm (median 8.3 cm, range 3.0-13cm) during 1st year then decreased to 6.9±2.4 cm (median 7.0 cm, range 3.0-12.5 cm) in the second year, and was maintained through the third year (mean 7.1±3.0 cm, median 7.0, range 3.0-13 cm). Among patients with GHD, those with primary deficiency had significantly better response to GHT in 1st year than secondary deficiency (9.0±2.65 vs 6.8±3.03 cm, p = 0.026). Response to GHT was negatively correlated with CA (r-0.27, p = 0.05), HA (r-0.47, p = 0.027) and BA (r-0.31, p=0.022) at presentation. Four patients (5.6%) developed hypothyroidism and one patient each developed disseminated tuberculosis and rickets. One patient of Turner's syndrome died of adrenal carcinoma. Short follow up and absence of measurement of IGF-1 and IGFBP3 were major limitations of this study. Conclusions. Response to GHT in Indian patients is comparable to western counterparts. Maximum height gain on GHT is during the first year than decreases in second year, but is maintained through third year. Patients with primary GHD had better response than secondary GHD. Response to GHT is negatively correlated with chronological, height and bone age at presentation.

The effect of growth hormone treatment on craniofacial growth in short stature children / 대한치과교정학회지

OBJECTIVE: The purpose of this study was to analyze the effect of growth hormone treatment (GHT) on craniofacial growth in children of short stature. METHODS: Nineteen untreated children of short stature were referred from the Pediatric Department, Yeungnam University Hospital as a subject group. All subjects had lateral cephalograms taken before, after 1 year and after 2 years of growth hormone treatment. As a reference group, we selected 19 normal children with paired sampling who matched the subjects' age and sex, from the Department of Orthodontics, Kyungpook National University Hospital. RESULTS: Before GHT, anterior cranial base length and upper posterior facial height, posterior total facial height, mandibular ramus length, and mandibular corpus length were significantly smaller in the reference group. In angular craniofacial measurements, saddle angle and mandibular plane angle were larger. SNA and SNB were smaller in the reference group. After two years of GHT, growth hormone accelerated growth in several craniofacial components. The posterior total facial height, the anterior, posterior cranial base length, and the mandibular ramus length were increased. And the difference in mandibular plane angle and ANB values compared with the reference group was decreased. CONCLUSIONS: GHT over 2 years leads to a craniofacial catch-up growth tendency, which is pronounced in interstitial cartilage and condylar cartilage.

Effects and adverse-effects of growth hormone therapy in children with Prader-Willi syndrome: A two year study / 소아과

PURPOSE: The objective of this study was to evaluate the effects and adverse side-effects of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). METHODS: Forty-one patients who had been treated with GH for more than two years (24 boys and 17 girls, mean age 7.3+/-3.3 years during treatment initiation) were enrolled for this study. RESULTS: After 2 years of GH therapy, the height and weight standard deviation scores (SDS) increased significantly (- 1.19+/-1.37 vs. - 0.02+/-1.45, and 1.02+/-2.42 vs. 1.63+/-2.22, P<0.002); however the percentage body fat decreased (44.6+/-9.9% vs. 38.1+/-10.5%, P<0.001). Further, no change was observed in the thyroid and serum glucose levels, but the total cholesterol level decreased. GH therapy did not impact glucose control in the patients with diabetes. The most common adverse effects of GH therapy were the progression of scoliosis and adenoid hypertrophy. CONCLUSION: GH therapy improved the height SDS and body composition in patients with PWS. However, GH should be used with caution in patients with scoliosis and adenoid hypertrophy.

Factors affecting the final adult height in survivors of childhood brain tumors / 소아과

PURPOSE: Short stature is an important complication that impairs the quality of life in survivors of childhood brain tumors. We studied their final adult height (FAH) to evaluate risk factors for short stature. METHODS: We reviewed the medical data of 95 survivors of childhood brain tumors (64 males and 31 females) who had been followed up from 1982 to 2006, reached FAH, and had a more than five year-disease-free survival. RESULTS: Final adult height standard deviation score (FAHTSDS: mean+/-SD) of the patients was lower than those of general population (-1.15+/-1.72), HTSDS at diagnosis (-0.13+/-1.57), and target HTSDS (-0.49+/-0.69). FAHTSDS of craniopharyngioma patients did not decrease (0.57+/-1.17), but those of germ cell tumor and medulloblastoma patients were significantly reduced (-1.20+/-1.45, -2.70+/-1.46; P<0.05). The patients treated with craniospinal radiation or chemotherapy had lower FAHTSDS (-1.93+/-1.58, -2.27+/-1.44; P<0.01). In the spinal irradiation group, the younger the age at diagnosis was, the more the loss of FAH (r=0.442, P<0.01). Growth hormone replacement (GHR) didn't improve FAHTSDS, but starting GHR under 12 years was an independent factor for improving FAH once treatment methods were taken into account (P=0.01). CONCLUSION: The younger age at diagnosis, spinal radiation and chemotherapy were all important risk factors of height loss, and height gain was expected in patients who received GHR under the age of 12 years. Therefore, regular check-ups of growth and early intervention with growth hormones are needed for high risk groups to improv

Significances of Echocardiography Using Tissue Doppler Imaging for Children in Growth Hormone Therapy

PURPOSE: The purpose of this study is to evaluate the functional changes of the ventricles for 27 children with recombinant human growth hormone (rhGH) therapy in short stature using echocardiography with tissue Doppler imaging. METHODS: The conventional Doppler echocardiography with tissue Doppler imaging were performed in 27 children with rhGH therapy for short stature and 13 healthy children. Peak velocities of systolic (S) and early (E'), late(A') diastolic wave of mitral annulus,septum and tricuspid annulus were obtained from apical 4 chamber view. RESULTS: There was no differences in left ventricle (LV) mass (72.948+/-11.825 m/s2 vs 73.931+/-12.093 m/s2, P=0.08), LV ejection fraction (66.778+/-5.441% vs 70.154+/-6.641%, P=0.095) and LV fractional shortening (36.737+/-4.265% vs 38.085+/-3.419, P=0.327) were observed between patients and controls. There was no significant differences in E and A measured at mitral and tricuspid annulus were observed between pateints and controls. There was no significant differences in S, E' and A' measured using tissue doppler imaging at mitral annulus, septum, and tricuspid annulus were observed between patients and controls CONCLUSION: No significant differences in parameters of cardiac function using tissue doppler imaging with conventional echocardiography were found between patients with rhGH therapy and controls. But, longer follow-up, involving at a larger number of patients, is required to confirm the safety of long-term rhGH treatment.

Clinical Characteristics and Growth Responses to GH Therapy in Children with Noonan Syndrome / 대한소아내분비학회지

PURPOSE:Noonan syndrome(NS) is characterized by short stature, congenital heart disease, and typical facies. Recombinant human growth hormone(GH) has been reported to improve growth rate in a similar fashion to that seen in Turner syndrome. We investigated the clinical characteristics and growth reponses to GH therapy in children with NS. METHODS:The cases of sixty seven patients with NS were reviewed retrospectively. Ten of the 65 patients were assessed height, weight and pubertal stage every 3 months during GH therapy. RESULTS:Webbed neck(70%), delayed development(59.7%), low set posterior hairline(56.7%), eye abnormalities(56.7%) and mental retardation(55.2%) were the leading clinical characteristics. Short stature below the 3rd percentile was presented in 73.8 %. Growth patterns in NS children were variable and the evaluation of their growth must be individualized. The increments of height SDS were significant in children with GH therapy(height SDS:from -2.8+/-.6 to -2.3+/-.9, growth velocity:from 4.4+/-.8 cm to 9.2+/-.9 cm during first year, and 6.1+/-.1 cm during second year) (P<0.05). CONCLUSION: This study characterized the clinical profiles in Korean children with NS, which should be further extended with more children with NS. Additionally, the significant increase in final adult height after GH therapy in children with NS should be observed.

Clinical Characteristics and Growth Responses to GH Therapy in Children with Noonan Syndrome / 대한소아내분비학회지

PURPOSE:Noonan syndrome(NS) is characterized by short stature, congenital heart disease, and typical facies. Recombinant human growth hormone(GH) has been reported to improve growth rate in a similar fashion to that seen in Turner syndrome. We investigated the clinical characteristics and growth reponses to GH therapy in children with NS. METHODS:The cases of sixty seven patients with NS were reviewed retrospectively. Ten of the 65 patients were assessed height, weight and pubertal stage every 3 months during GH therapy. RESULTS:Webbed neck(70%), delayed development(59.7%), low set posterior hairline(56.7%), eye abnormalities(56.7%) and mental retardation(55.2%) were the leading clinical characteristics. Short stature below the 3rd percentile was presented in 73.8 %. Growth patterns in NS children were variable and the evaluation of their growth must be individualized. The increments of height SDS were significant in children with GH therapy(height SDS:from -2.8+/-.6 to -2.3+/-.9, growth velocity:from 4.4+/-.8 cm to 9.2+/-.9 cm during first year, and 6.1+/-.1 cm during second year) (P<0.05). CONCLUSION: This study characterized the clinical profiles in Korean children with NS, which should be further extended with more children with NS. Additionally, the significant increase in final adult height after GH therapy in children with NS should be observed.

A Case of Severe Hypertension associated with Growth Hormone Therapy / 대한소아내분비학회지

The use of recombinant DNA technology to produce human growth hormone has resulted in a marked increase in availability of Growth Hormone(GH) to treat short stature due to GH deficiency and other conditions, such as Turner syndrome, familial short stature, chronic renal insufficiency and intrauterine growth retardation (IUGR). But, the GH therapy may result in the adverse events such as sodium and water retention, pseudotumor cerebri, slipped capital femoral epiphysis, growth of nevi, recurrence of tumor. We experienced a case of severe hypertension associated with GH therapy in a 14-year-old male who presented high blood pressure up to 190/100 mmHg and normalized at 2-3 weeks after discontinuation of GH. Therefore, we think that the blood pressure should be carefully monitored during GH therapy.

Two Cases of Growth Hormone Therapy in Idiopathic Dilated Cardiomyopathy

Growth hormone receptor gene is expressed in the myocardium and growth hormone(GH) administration has been shown to increase cardiac insulin-like growth factor-I(IGF-1) contents. The cardiac myocyte express IGF-I receptors and IGF-I promotes cardiac hypertrophy. Furthermore GH therapy has been reported to have beneficial effects in the treatment of dilated cardiomyopathy in adults. We have studied the effect of short term growth hormone treatment in two cases of a 5 year-old girl and a 15 year-old boy presenting idiopathic dilated cardiomyopathy. Transthoracic echocardiography revealed that the left ventricular chamber was markedly dilated and the global left ventricular systolic function was severely reduced in both. Medical treatments such as inotropic agents, diuretics and angiotensin converting enzyme(ACE) inhibitor were tried but we could not attain remarkable improvement. Finally, we started growth hormone treatment (0.35 U/kg/week, Eutropin, LGCI, Korea) and after treatment for 3 months, we attained a remarkable hemodynamic improvement in the 5 year-old girl with remarkable IGF-I increase after GH treatment, but not in the 15 year-old boy without IGF-I increase. The treatment was safe without side effects. However, no beneficial effects on cardiac function or structure were detected at 6 months of post-treatment.

Response of Growth Hormone Treatment to Final Height in Children with Growth Hormone Deficiency and Familial Short Stature / 대한소아내분비학회지

PURPOSE: A number of studies have been published on the effect of growth hormone therapy over 1-3 years in children with growth hormone deficiency(GHD) & Familial short stature(FSS). So far final height data are seldomly available. Final heights of GH treated children with GHD & FSS were evaluated. METHODS: 10 Children with GHD and 69 children with with FSS were enrolled for the study. They were treated with GH 0.1IU/kg/daily in 10 GHD and 20 children with FSS. They were grown up and reached adult height. 49 children with FSS were not treated at all. Facors influencing final height were investigated. RESULTS: 1) All patients with GHD(Idiopathic 8 cases, Organic 2 cases) had additional gonadotropin deficiency and had multiple pituitary hormone deficiency. 2) At start of GH treatment boys of idiopathic GHD were 9.8 years old and 12.4 years old in girls and their mean height was 114.8cm(-2.8SDS), 123.0cm(-2.9 SDS)in boys and girls respectively. Boy with orgnaic GHD was 11.1 years and 6.7 years old in girl. Their height were 126.0cm(-1.5SDS) and 104cm(-1.2SDS) respectively. 3) Mean final height of idiopathic GHD was 167.6cm(-0.5SDS) in male and 161.0 cm(0.7SDS) and that of organic GHD was 173.0cm(0.5SDS) in male and 157cm (0SDS) in girl. 4) Mean Final height in untreated children with FSS was 159.8+/-.2cm(-1.6 SDS)in male and 149.6+/-.3cm(-1.4SDS) in female. Mean final height of GH treated in FSS was 162.5+/-.1cm(-1.5SDS) in male and 152.0+/-.4cm(-1.2SDS) in female But there was no statiscally difference between untreated and treated children in final height. 5) The age of onset of menarche was 12.74+/-.78 years old in GH treated group (n=12) and 12.45+/-.16 years old in untreated group(n=34). CONCLUSION: The GH administration in patients with GHD has been confirmed for growth promotion. but in case of FSS there was no significant difference between treated and untreated group. More further studies are needed for the confirmation of the efficacy of GH therapy in patients with FSS.

A Case of Beneficial Effect of Short-Term Growth Hormone Treatment for Intractable Heart Failure in Cardiomyopathy Combined with Neuromuscular Dystrophy

We report a case of 15-year-old man with beneficial effects of short term growth hormone treatment presenting with cardiomyopathy combined with neuromuscular dystrophy. Transthoracic echocardiography revealed that LV chamber was markedly dilated and global LV systolic function was severely reduced. The findings of electromyography were compatible with neuromuscular dystrophy. Under the impression of cardiomyopathy combined with neuromuscular disease, maximal medical treatments such as inotropic agents, diuretics and ACE inhibitor were tried but we could not attain remarkable clinical improvement. Finally, we started growth hormone injection and after treatment for 3 months, we could attain remarkable clinical and hemodynamic improvement without any side effect.

The Relationships of Pretreatment IGF-I SDS, Delay in Bone Age and Response to Recombinant Human Growth Hormone (rhGH) Therapy in Children with Growth Hormone Deficiency

PURPOSE: To assess whether pretreatment IGF-I SDS and pretreatmental bone age are useful indicators in the response of rhGH therapy in children with GH deficiency (GHD), the relationship between pretreatment IGF-I SDS, delay in bone age and the growth response during the first year of rhGH treatment was analyzed. METHODS: This study included 12 children with GHD. We measured IGF-I levels by RIA after acid-ethanol extraction at pretreatment and then calculated IGF-I SDS as follow: SDS = (IGF-I- mean IGF-I for normal subjects of the same age and sex)/SD of IGF-I for normal subjects of the same age and sex. GH levels were measured by immunoradiometric assay. All patients were treated with rhGH, 0.1IU/kg daily, 6 times a week for 1 year. RESULTS: Twelve patients (6 males and 6 females), age distribution from 4 to 16 years, were studed. The data is reported as the mean +/- SD. Height SDS for chronologic age of the group as a whole as -3.6 +/- 1.0 and bone age was 8.2 +/- 3.4 years. Pretreatment height velocity (HV) was 4.0 +/- 1.7cm/yr and the HV during each 3 months of therapy were 10.1 +/- 4.5cm/yr, 9.6 +/- 4.5cm/yr, 8.5 +/- 4.3cm/yr and 7.8 +/- 1.3cm/yr, respectively and therefore the HV during the first year of rhGH therapy increased to 9.3 +/- 2.9cm/yr (P=0.002). Pretreatmental IGF-I SDS was -2.2 +/- 0.9 (-0.4~-3.6). A significant negative correlation between pretreatmental IGF-I SDS and incremental height gain was obtained (r=-0.40, P<0.05). The height velocity of the group whose pretreatmental IGF-I SDS was below -2 (n= 8) as a whole increased significantly from 3.5 +/- 1.8cm/yr to 10.3 +/- 2.9cm/yr (P=0.001). Pretreatmental bone age delay was 3.1 +/- 1.9 (0.5-7.8) years. The height velocity of the group whose pretreatmental bone age delay above 2 years (n=9) increased significantly from 4.1 +/- 1.1cm/yr to 9.7 +/- 2.9cm/yr (P=0.001). CONCLUSION: The height velocity of GH deficient children whose pretreatmental IGF-I SDS below -2 or pretreatmental bone age delay above 2 years increased significantly after rhGH therapy. It suggests that the pretreatmental IGF-I SDS and pretreatmental bone age may be significant indicatiors in the response of GH therapy in children with GHD.

Etiological Classifications of Children with Chief Complaint of Short Stature / 대한소아내분비학회지

Purpose : As the recombinant human growth hormone has been widely available, a lots of parents having short statured children are interested in promoting growth of them whatever the etiologies of short stature they have. However, the growth hormone therapy for growth-promoting effect is only justified in well-established indications such as growth hormone deficiency, fumer syndrome, and chronic renal insufficiency. This study was undertaken to classify the children with chief complaint of short stature by its cause and giving the basic epidemiologic data for it so that the size of population in which growth hormone is indicated can be estimated. Methods : According to Ranke's etiologic classification, we categorized the 579 children who visited our pediatric endocrinology clinic with chief complaint of short stature during the period of March 1994 to August 1996. In this prospective study, history regarding growth was taken, physical examination and laboratory tests including bone age, thyroid function, blood chemistry were carried out. The auxological data were analyzed. Additional chromosomal study or growth hormone provocative tests were performed when needed. Results : Out of 579 patients, 360(62.2%) were classified as normal and 127(21.9%) were classified as normal variants which consist of familial [74(12.8%)], constitutional [48(8.5%)], and mixed familial & constitutional short stature[5(0.9%)]. Pathologic short stature was found in only 80(13.8%). Those are growth hormone deficiency(28), Tumer syndrome(16), intrauterine growth retardation(14) in order. Other etiologies list varieties of dysmorphism, skeletal dysplasia, chromosomal disorders. Conclusions : This results suggest the vast majority of children with chief complaint of short stature are normal or normal variants. Only 7.8% of children who visited our clinic were indicated for growth hormone therapy.

Cardiovascular Effects of Growth Hormone Treatment in Idiopathic Short Stature

PURPOSE: An excess of GH causes various problems within the cardiovascular system including cardiac hypertrophy and abnormalities of left ventricle (LV) function. To evaluate the cardiovascular effects due to GH treatment in idiopathic short stature (ISS), we measured the cardiovascular function. METHODS: Twenty-two echocardiographic studies were performed in ISS who were admitted from Jan. 1994 through Jul. 1996, and they were divided into two groups which revealed in 11 children with GH treatment and in 11 children without GH treatment. RESULTS: The results obtained were as follows, 1) The mean HR in GH group was significantly lower than that of control group (79.9+/-12/min vs. 90.2+/-9/min) (p<0.05), and the mean BP was the GH group 81.6+/-10mmHg and control group 77.7+/-7mmHg. 2) The mean LV isovolumic contraction time (LICT) in GH group was significantly longer than that of control group (35.6+/-3 vs. 32.3+/-2) (p=0.01), but within normal limits. And in GH group, the mean shortening fraction (SF), mean velocity of circumferential fiber shortening (mVcf), and systolic time interval (STI) were 33.9+/-3%, 0.99+/-0.2cir/sec, and 0.15+/-0.04, respectively. In control group, the mean those values were 33.4+/-5%, 0.95+/-0.2cir/sec, and 0.15+/-0.04, respectively. 3) In GH group, the mean isovolumic relaxation time (IRT), peak E velocity (E), peak A velocity (A), and Ea/Aa ratio were 0.05+/-0.01sec, 113.5+/-18cm/sec, 60.5+/-14cm/sec, and 3.9+/-2, respectively. In control group, the mean those values were 0.06+/-0.01sec, 117+/-1.4 cm/sec, 56.8+/-13cm/sec, and 4.7+/-2, respectively. 4) In GH group, the mean cardiac index (CI) and systemic vascular resistance (SVR) were 4304+/-1660ml/min/m2 and 6330+/-764mmHg/ml. In control group, the mean those values were 3835+/-838ml/min/m2 and 6218+/-588mmHg/ml. CONCLUSIONS: These results suggest that the cardiovascular effects did not differ from those in the controls and remained within the normal range after a mean GH treatment duration of 6.2 months.

The Changes of the Bone Mineral Density in the Girls with Turner Syndrome, using Recombinant Human Growth Hormone

PURPOSE: Estrogen deficiency causes sexual infantilism in Turner syndrome, which could decrease the bone mineral density(BMD) since birth. This decreased BMD might be contributed by the decreased growth hormone(GH) secretion. To improve the decreased BMD, estrogen therapy is recommended, especially after the pubertal age, but estrogen therpay during childhood can accelerate the epiphyseal fusion, resulting in shorter final height. There is a possibility that GH therapy not only ameliorates the final height, but also improve the decreased BMD, because GH is known to be involved in the normal bone metabolism. We observed whether GH therapy, given to improve the growth velocity, can change the BMD in the girls with Turner syndrome. METHODS: Thirteen prepubertal girls with Turner syndrome, who were confirmed by clinical and chromosomal examinations, were given GH(1 U/kg/week, daily, subcutaneous) for one year. During GH therapy, BMDs were mesured by DEXA(dual energy X-ray absorptiometry at trochanter and lumbar spine between the second and fourth vertebra. Growth velocity significantly increased during GH therapy and bone age were significantly advanced during this period. RESULTS: 1) The BMD of femur neck was significantly increased from 0.59+/-0.09 gm/cm2 before therapy to 0.73+/-0.07 gm/cm2 and 0.81+/-0.06 gm/cm2 at 6 and 12 months of therapy, respectively(p<0.01, Fig. 2). 2) The BMD of 2nd lumbar spine did not change during GH therapy. 3) The BMD of 3rd lumbar spine was decreased with marginal significance from 0.73+/-0.09 gm/cm2 before therapy to 0.66+/-0.09 gm/cm2, 0.65+/-0.05 gm/cm2 after 6 and 12 months of therapy, respectively(p=0.05). 4) The BMD of 4th lumbar spine was significantly decreased from 0.75+/-0.06 gm/cm2 before therapy to 0.69+/-0.10 gm/cm2, 0.64+/-0.08 gm/cm2 after 6 and 12 months of therapy, respectively(p<0.01, Fig. 2). 5) There was no significant correlation between the changes of the BMD and Bone or chronological age at initial GH therapy. Conclusion : The positive effect on BMD of GH therapy seems to be dependent on the specific area of skeletal system, where GH might exerts its effect, regardless of the existence of estrogen effect. The BMDs of another areas of skeletal system, where GH does not exert its effect, did not change with GH therapy and rather decreased by probably unknown mechanisms and GH therapy. These unknown mechanisms partially might involve the estrogen defect on BMD, This should be remained to be clarified with more patients and longer duration of study.

Three years of growth hormone therapy in children with growth hormone deficiency.

The objects is to study the long-term therapeutic effect of recombinant DNA hGH by administration of biosynthetic hGH for 2 ½ - 3 years to 12 children with growth hormone (GH) deficiency, consisted of 7 males, 5 females; whose ages ranged from 3 years 4 months to 17 years old. All patients fulfilled the criteria of GH deficiency namely; growth rate less than 7 ng/ml after clonidine and dopa-propranolol stimulation test. Ten patients had idiopathic GH deficiency. Two had hypopituitarism as a result of brain tumors and cranial surgery. The growth rate was observed over a pretreatment period of 12 months. The patients received 0.1 µ/kg of recombinant DNA hGH subcutaneously 6 days per week. In males with GH-deficiency, pre-treatment mean height was 2.6 cm per year. The mean height increment at 6th, 12th, 24th, 30th, and 36th month of treatment were 6, 11.2, 14.1, 17.6, 20.6 and 23.4 cm respectively. The females had mean height increment during pre-treatment period of 2.2 cm per year. The mean height increment on 6th, 12th, 18th, 24th, and 30th month of treatment were 4.7, 7.8, 10.3, 14.2 and 14.4 cm respectively. All patients have a significant satisfactory response to recombinant DNA hGH in term of height increment. There was no report of either side effect or complication. Every patient has had improved sense of physical, mental and psycho-social well-being.