Effects of 3 Years of Growth Hormone Therapy in Short Normal Children

ABSTRACT. The effect of 3 years of growth hormone (GH) treatment on growth rate, predicted height, carbohydrate and metabolic status, and thyroid function was studied in 16 short prepubertal children growing with a normal pretreatment growth rate. The height velocity SDS increased from a pretreatment value of -0.44 ± 0.33 (mean ± SD) to a value of +2.20 ± 1.03 during the first year of treatment. It was maintained at a value above zero over the subsequent 2 years. By the end of the third year of treatment, the predicted final height had increased by 6.8 cm in the boys and by 4.2 cm in the girls ( p < 0.001 and p < 0.01, respectively). Increasing the dose of GH on a body surface area basis reduced the deceleration of growth observed during the second year of treatment, leading to an improvement in height prognosis over that year. Glucose homoeostasis was achieved initially at the expense of an elevation in fasting serum insulin concentration, but this had returned to pretreatment values by the end of the second year of therapy. No effects on thyroid function were observed.     

The Effect of Recombinant Human Growth Hormone Therapy on Left-Ventricular Chamber Size and Function in Children With Growth Hormone Deficiency

This study was designed to assess the effect of recombinant human growth hormone (rhGH) therapy on left-ventricular (LV) chamber size and function in children with idiopathic isolated growth hormone deficiency (GHD) using conventional echocardiography and tissue Doppler imaging (TDI). Thirty patients (19 boys and 11 girls) with idiopathic isolated GHD were followed-up for 12 months. Mean age of patients was 11.0 ± 2.6 years (range 6.3–15.5). At baseline and at 3, 6, and 12 months of treatment, the structure of the left ventricle was assessed by conventional echocardiography and myocardial rates and time intervals by TDI. There was a significant increase in LV mass (LVM) compared with pretreatment values. Like LVM, relative wall thickness (RWT) was also increased significantly. The significant increase in LVM indexed to body surface area and RWT became apparent at month 3 of treatment with a significant increase in LVM indexed to height^2.7 at treatment month 6. Normalized LVM increased as early month 3 of treatment, and a steady increase was observed until month 12. However, no patient had LVM > +2 standard deviation scores at month 12 of treatment. No significant differences were observed in functional parameters of the left ventricle and the interventricular septum. The results of this study showed that rhGH therapy causes an increase in myocardial mass without changing the geometry or function of the myocardium. Therefore, the increase in myocardial mass appears to be concentric, thus causing remodeling instead of hypertrophy.     

A Controlled Trial of Methionyl Growth Hormone Therapy in Prepubertal Children with Short Stature, Subnormal Growth Rate and Normal Growth Hormone Response to Secretagogues

ABSTRACT. Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group ( n = 20) undergoing treatment with methionyl GH (somatrem), 2IU per m² body surface s.c. daily, or a control group ( n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity ( r = 0.8) and the short-term height velocity increment ( r = 0.7–0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Nasopharyngeal carcinoma in children and young adults—Beyond 5‐year survival

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of NPC includes chemotherapy and radiotherapy. With current treatment protocols, survival rates for patients with nonmetastatic disease is over 80%. Data regarding very late events including long‐term treatment‐related morbidities and second malignancies are scarce. We present our data on 42 patients with NPC treated in Israel between 1989 and 2014, and followed until 2019. During follow up, five patients had disease recurrence, and four children developed secondary malignancy. Median time to diagnosis of secondary malignancy was 105 months. Eighty‐eight percent of patients have long‐term treatment‐related morbidities.     

Clinical Evaluation of the Needle-free Injection System VISION? for Growth Hormone Therapy in Children

The aim of this study was to compare the therapeutic effects of rhGH administered either by subcutaneous needle-injection (pens) or subcutaneous needle-free jet-injection (VISION^®). Furthermore, a survey was carried out after using VISION^® for 12 mo. A needle-free injection group consisting of 18 subjects (11 males and 7 females, mean age 5.87 ± 2.05 yr at the start of hGH therapy) who have not used pen injectors to date, were allowed to use VISION^® in their third to fifth years of GH therapy. In addition, a group of 8 subjects who had been using pen injectors at our clinic (6 males and 2 females, mean age 6.54 ± 2.78 at the start of GH therapy) was monitored as a control. The results indicate that there are no significant differences between the mean growth rates, growth rate SD scores or height SD scores when comparing injection devices. Furthermore, the survey of VISION^® revealed that 70% of the subjects found it slightly or not painful at or after injection, 70% found VISION^® very easy or easy to use, and 80% found the weight of the device appropriate. All subjects expressed a desire to continue using VISION^® in the future. Our results suggest that there are no problems with the effectiveness of hGH treatment with VISION^®, a needle-free jet-injection device and that VISION^® is an effective device for children who have an aversion to needle injection.     

Assessment of Psychosocial Status among Short-stature Children with and without Growth Hormone Therapy and Their Parents

To evaluate the psychosocial status of short children with and without growth hormone therapy (GHT) and that of their parents, self-administered questionnaires were collected from patients and parents who regularly visit the outpatient clinics participating in the Child Health and Development Network. Completed questionnaires were received for one hundred and thirteen patients with GHT and 67 patients without GHT. According to the parents, both children with GHT and without GHT have no difficulty in their daily lives (89% vs. 95%) and are positive (56% vs. 65%), respectively. Ninety-eight percent of parents of children with GHT and 83% of parents of children without GHT had expected the current treatment strategy to be effective. Parents of children with GHT are more satisfied with the current therapy than those without GHT (79% vs. 50%), and feel less anxiety about the on-going therapy than (31% vs. 58%, respectively). Children treated with or without equally reported having no difficulty in their daily lives (90% vs. 93%), and being positive in their lives (81% vs. 75%, respectively) despite their short stature. Although less than one third of the patients have been bullied in their classroom (26% with GHT vs. 29% without GHT), younger and shorter children tend to be bullied more often. Short children undergoing GHT and their parents have anxiety regarding their height and expectations of the effect of GHT. It is important for doctors to inform their patients regarding realistic height expectations before starting GHT. Additionally, medical consultation is recommended for patients who remain below –2 SD in height despite GHT.     

重组人生长激素治疗对儿童甲状腺功能和骨骼的影响

现介绍了重组人生长激素(rhGH)的作用机制及其对儿童骨骼发育、甲状腺轴功能的影响.其中详细阐述了垂体-甲状腺轴与垂体-生长激素轴对骨骼生长发育的相互作用,从而明确了rhGH替代治疗对这2个与儿童生长发育至关重要的内分泌轴功能的影响.并进一步明确了rhGH治疗可能干扰儿童骨骼发育及甲状腺轴功能不良反应的发生率及治疗方案.     

Effect of Recombinant Human Growth Hormone Therapy on Bone and Clinical Parameters in Girls with Turner's Syndrome

Ferrández, A., Mayayo, E., Arnal, J.M., Garcia, C., Buduel, C., Lasarte, J.J., Anton, R., hyuelo P., and The Spanish Collaborative Group (Endocrine Unit, Children's Hospital, Miguel Servet, Zaragoza, Spain). Effect of recombinant human growth hormone therapy on bone and clinical parameters in girls with Turner's syndrome. Acta Paediatr Scand [Suppl] 356: 87, 1989.
Forty-eight girls with Turner's syndrome were assigned to one of three treatments; recombinant human growth hormone (rhGH) alone, rhGH plus oxandrolone, and rhGH plus ethinyloestradiol. Treatment with rhGH alone or in combination with oxandrolone induced catch-up growth. Older girls treated with rhGH plus ethinyloestradiol showed less marked improvement. The gain in height was associated with a gain in bone diameter and cortical thickness (reflecting increased bone mass). There was a rapid loss of subcutaneous fat. These effects of growth hormone are similar to those observed in patients with growth hormone deficiency.     

Favorable Impacts of Growth Hormone (GH) Replacement Therapy on Atherogenic Risks in Japanese Children with GH Deficiency

Growth hormone (GH) affects body composition and atherogenic risk factors. Severehyperlipidemia may develop in GH-deficient adults as a consequence of continuous GHdeficiency. We investigated changes in lipid profiles in 158 Japanese children (103 boysand 55 girls) with GH deficiency who had been enrolled in the Pfizer International GrowthDatabase Japan during 3 yr of GH replacement therapy to evaluate whether GH treatment hasbeneficial effects on atherogenic risk factors. Total cholesterol (TC), high-densitylipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and atherogenicindex were evaluated before treatment and then once a year during treatment. The meanbaseline TC was within the normal range in both boys and girls. Seventeen (16.5%) of the103 boys and 18 (32.7%) of the 55 girls, however, had a TC level over 200 mg/dl beforetreatment. The mean TC level showed a significant decrease in girls. In a separateanalysis, patients of both sexes with a TC level > 200 mg/dl showed significantlydecreased TC. LDLC decreased significantly only in girls, while HDLC showed no change ineither sex. The atherogenic index decreased significantly in girls. GH replacement therapyin children with GH deficiency had beneficial effects on lipid metabolism and atherogenicrisk in both sexes. Early GH treatment would produce lipid metabolism benefits in thesepatients.     

Cardiac Failure and Dysrhythmias 6–19 Years After Anthracycline Therapy: A Series of 15 Patients

The clinical course of late symptomatic anthracycline cardiomyopathy, and resultant changes of cardiac function, were described in 15 patients. They represented a subset of 300 patients who had cardiac evaluations to identify the prevalence of late cardiotoxicity more than 4 years after anthracycline therapy in these patients. The clinical course and all available cardiac evaluations including electrocardiography, continuous taped electrocardiography, echocardiography, radionuclide cardiac angiography, cardiac catheterization, and endomyocardial biopsy, of the 15 patients were reviewed. The patients had received 285–870 (median 540) mg/M² of daunorubicin and/or doxorubicin 6–19 (median 12) years prior to the onset of late symptoms. Seven patients also had 2,100–4,000 cGy mediastinal radiotherapy. Five patients had required treatment for cardiac symptoms at the end of chemotherapy but 10 patients had no cardiac problems anteceding their late decompensation. Fractional shortening on echocardiogram at late decompensation was 8–20% (median 17%) and radionuclide left ventricular ejection fraction was 8–59% (median 38%). All were treated with digitalis and diuretics and 13/15 with afterload reduction, with at least transient improvement of symptoms. They were followed for 1–9 (median 3) years after late decompensation. One died of uncontrollable cardiac failure. Another underwent successful cardiac transplantation. Conduction abnormalities and dysrhythmias were present in 14/15 patients and 3 died suddenly. Two more had syncope, one requiring an automatic cardiac defibrillator. Endomyocardial biopsy or autopsy revealed hypertrophy and fibrosis in 10/10 patients. Our patients with early cardiac symptoms improved transiently but decompensated later and patients with no early symptoms developed cardiac symptoms more than 10 years after anthracycline therapy. Therefore, patients who have received anthracyclines should have continued cardiac evaluation. © 1995 Wi1ey-Liss, Inc.     

Predictive Criteria for Successful Growth Promotion in Growth Hormone Therapy of Short Stature: A Comparison between Common Endocrine Parameters and Knemometry

ABSTRACT. Due to increased availability of growth hormone (GH) for the treatment of short stature, its use has been proposed for a number of conditions besides classic GH deficiency. We have studied growth response during a one year treatment period with 14 IU/m²/week of GH in a heterogenous group of 24 short children with various conditions associated with short stature (SDS for body height ranging between −2.2 and −4.4). Thirteen children could be classified as "responders" with growth rate increments of 2 cm/yr or more above pretreat-ment growth rates, and 11 children as "non-responders". The children were measured regularly both by stadiometry and knemometry at weekly intervals. GH stimulation by insulin, arginine and spontaneous overnight secretion of GH, and SM-C generation were evaluated in the children and found to be of no predictive value for the individual responsiveness to GH administration except in one boy with classic GH deficiency. However, serial measurements of the lower leg length provided useful information for individual predictions in 21 out of the 24 children as early as 10 weeks after the start of the GH treatment.     

Growth,neurological and cognitive development in infants with a birthweight <501 g at age 5 years

Aim: To determine growth, neurological and cognitive development at 5 years of preterm infants with birthweights <501 g born in three German tertiary perinatal centres between 1998 and 2001. Methods: Structured neurological examination, the Gross Motor Function Classification Scale and the Kaufman‐Assessment‐Battery Test for Children. Results: Of 107 infants, 48 received immediate life support (gestational age 25.2 weeks [21–30.7]; birth weight 435 g [290–500]) median [range]), 27 (56%) survived until follow‐up [95% CI 39–69%], 19 (70%) could be tested. In few infants had catch‐up growth taken place. Neurological test results were normal in five infants (26%) and mildly abnormal/severely abnormal in 11 (58%)/3 (16%) infants. Visual impairment was present in eight (42%), and hearing disability in three (16%). The mean mental processing composite (IQ) was 82 [50–104] (median [range]). Conclusion: Of all resuscitated infants with a birthweight <501 g, 56% survived to school age. Of these, composite outcome score showed normal development or mild disability in one‐half, and moderate or severe disability in the other half of them. Investigators should include such infants in studies and their reports should give specific information about them.     

Identification of viral infections in pregnancy by assay of (2′–5′)-oligo-isoadenylate synthetase

Interferons are produced in response to viral infections. Among the biochemical changes they cause in cells is the induction of the enzyme (2′–5′)-oligo-isodenylate synthetase. The activity of this enzyme can be measured and this can indicate exposure and response of cells to interferon. The efficacy of such an assay of peripheral blood of pregnant women may aid in establishing screening guidelines for potentially teratogenic viral infections.

The blood of 44 primigravidas with complaints of fever, myalgia, cough, vaginal discharge and/or costovertebral angle tenderness was assayed for activity of the enzyme (2′–5′)-oligo-isoadenylate synthetase and compared to assays of the enzyme activity in a group of 37 healthy primigravidas which served as a control group. It was found that the group with viral infections had an increase in enzyme activity from twice to 15 times the normal value, with characteristic rises of enzyme activity in several viruses known or suspected to cause human defects.

Several general guidelines are proposed to assist the obstetrician in determining a viral etiology of acute illness in pregnancy, It is suggested that the assay of enzyme activity of (2′–5′)-oligo-isoadenylate synthetase may provide a simple tool for rapid diagnosis of viral infections in pregnancy.     

短期生长激素治疗对营养不良矮小儿童血糖、甲状腺功能、胰岛素生长因子-Ⅰ、胰岛素生长因子结合蛋白-3的影响

目的探讨重组人生长激素(rhGH)短期治疗对营养不良矮小儿童空腹血糖(GLU)、甲状腺功能(TF)、胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合蛋白-3(IGFBP-3)的影响。方法选取16例年龄2～12岁、符合营养不良矮小诊断的患儿。采用rhGH治疗3个月。分别在治疗前、治疗1和3个月,取患儿清晨空腹血,测定GLU、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺素(TSH)、IGF-Ⅰ、IGFBP-3水平。采用方差分析比较3个时间点测量指标的均数。结果营养不良矮小儿童经rhGH治疗1和3个月后,GLU、T3、T4、TSH、IGFBP-3均无明显变化(Pa>0.05),IGF-Ⅰ明显高于治疗前,且有统计学意义(P<0.05)。结论rhGH短期治疗能使营养不良性矮小儿童的IGF-Ⅰ升高,且不影响GLU、TF。     

5-fluorouracil and cis-platinum in the treatment of refractory solid tumors: A pediatric oncology group phase I — II study

Eleven patients with osteogenic sarcoma (9), Hodgkin disease (1), and mesenchymal sarcoma (1), were treated with 5-fluorouracil (5-FU) and cisplatin (DDP). Myelosuppression and vomiting of variable degrees occurred in all. No responses were seen.