Malignant thymoma in a patient with growth hormone deficiency during growth hormone therapy

Malignant thymoma was found in an 8-year-old Japanese boy with growth hormone (GH) deficiency who had received GH therapy for 3 years and 5 months. There may be a possible relationship between the occurrence of malignant thymoma and GH therapy.     

Wilms tumour in a patient with growth hormone replacement therapy

Wilms tumour was found in a Japanese boy aged 5 years 9 months with isolated growth hormone (GH) deficiency and some congenital anomalies. He had received pituitary GH replacement therapy from the age of 2 years 1 month to 4 years 7 months and after a 1 year interval he received biosynthetic GH for 2 months until the tumour became clinically apparent. This was the sixth known patient with GH deficiency to develop a malignant neoplasm during or after GH replacement therapy and the first with a solid tumour in Japan since 1975, when treatment with pituitary GH for patients with GH deficiency was introduced.     

Three-year results of a randomized prospective trial of methionyl human growth hormone and oxandrolone in Turner syndrome

Seventy girls with Turner syndrome, 4 to 12 years of age, participated in a prospective, randomized study to determine the effects on growth of methionyl human growth hormone (met-hGH) or oxandrolone. Subjects were randomly assigned to receive either no treatment (control) or met-hGH (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination met-hGH plus oxandrolone. At the end of an initial period of 12 to 20 months, patients in the original control and oxandrolone groups were given combination met-hGH plus oxandrolone. At that time the dosage of oxandrolone was lowered to 0.0625 mg/kg/day. Sixty-five subjects have now completed the first 3 years of the study. Compared with the control growth rate for year 1 (3.8 cm/yr), significant increases in growth rate were seen in all 3 years of combination therapy (9.8, 7.4, and 6.1 cm/yr, respectively) and in the first 2 years of treatment with met-hGH alone (6.6, 5.4, and 4.6 cm/yr). When growth velocity was expressed as standard deviation for age in girls with Turner syndrome, significant increases relative to the control group for year 1 (-0.1 SD) were seen in all three years of both combination therapy and met-hGH alone (combination, +6.6, +4.3, +3.0 SD; met-hGH, +3.1, +2.0, +1.4 SD). After 3 years of treatment, predicted adult height by the method of Bayley-Pinneau increased 4.5 cm in the met-hGH group and 8.2 cm in the combination group.     

A controlled trial of methionyl growth hormone therapy in prepubertal children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group

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), 2 IU 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.     

Two-year results of treatment with methionyl human growth hormone in children with Turner syndrome. Dutch Growth Hormone Working Group

Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m2 body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 microgram/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.     

Ganglioneuroma of left adrenal gland in a patient with Turner syndrome during growth hormone therapy

We report on a Japanese girl with Turner syndrome (45,XO) who developed ganglioneuroma of the left adrenal gland during growth hormone (GH) therapy. She had received GH replacement therapy from the age of 6.8 years. At the age of 10.3 years, abdominal ultrasonography revealed a mass which occupied the upper area of her left kidney. Computed tomography and magnetic resonance imaging of the abdomen showed a low density mass with a smooth surface located between the upper portion of the left renal vein and the pancreas. Microscopic examination resulted in a diagnosis of ganglioneuroma of the left adrenal gland. At present we cannot conclude that patients who have received GH replacement therapy are at higher risk for developing tumors compared to those without GH replacement therapy.     

Crouzon综合征合并生长激素缺乏症1例报告及重组人生长激素治疗随诊

目的报告1例Crouzon综合征合并生长激素缺乏症(GHD)患儿及其重组人生长激素(rhGH)治疗结果。方法回顾分析患儿以rhGH治疗2年的临床资料。结果患儿女性,5岁4月龄时身高98.2 cm(P_3),有特殊面容(舟状头、突眼、反颌畸形等)。基因检测示FGFR2基因存在c.1061CG(p.Ser354Cys)杂合变异,源自母亲,为已知的致病变异,诊断为Crouzon综合征。同时相关检查提示患儿合并GHD。给予rhGH治疗2年,身高117 cm,平均生长速率为9.4 cm/a。治疗期间,头颅磁共振监测提示侧脑室及第三脑室略扩张等表现未进展,眼科随诊示左眼视盘水肿程度较前减轻,未发现不良反应。结论矮小可能是Crouzon综合征的表型,rhGH治疗可以改善Crouzon综合征合并GHD患儿的身高,且未引起患儿颅内压增高等不良反应。     

Effective growth hormone therapy in a growth hormone deficient patient with Duchenne muscular dystropy without evidence of acceleration of the dystrophic process

We describe a patient with Duchenne muscular dystropy and growth hormone deficiency in whom treatment with human growth hormone for 2 years resulted in improved growth velocity without any detrimental effect on muscle strength.     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

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生长激素缺乏症(GHD)是儿童生长迟缓(矮身材)的常见病因,1956年首次从人垂体中成功分离及提纯了人垂体生长激素(phGH),成为GH研究的标志性进展。1958年phGH用于治疗首例GHD患儿并成功地获得促生长疗效。但是,于1962~1985年3000例接受过phGH治疗的患儿中150例不幸染上Creutzfeldt-Jakob病(CJD)———致命性的脑炎。其原因归咎于垂体抽提过程中被朊病毒(prion)污染,而非GH本身。1985年phGH被禁止应用。同年,无CJD危险的基因重组人生长激素(rhGH)被美国FDA批准用于GHD治疗。rhGH是应用重组DNA技术,于1979年首次成功地使人生长…     

国产重组人生长激素治疗生长激素缺乏症疗效观察

目的　正确评价国产重组人生长激素 (rhGH)治疗儿童生长激素缺乏症 (GHD)的疗效和安全性。方法　GHD 5 7例 ,予国产rhGH 0 .1U/(kg·d) ,疗程 6个月。并对其疗效进行观察。 结果　身高由 (12 0 .5±15 .9)cm增至 (12 6 .9± 14 .1)cm ,生长速率由 (2 .2± 1.2 )cm/年增至 (12 .8± 2 .7)cm/年 ,身高落后SD值由 (-5 .0± 2 .8)减至 (- 4 .0± 2 .3)。血清胰岛素样生长因子 1由 (48.2± 18.8) μg/L增至 (12 0 .2± 6 2 .4 ) μg/L。血清碱性磷酸酶由 (14 9.8± 6 0 .4 )U/L增至 (2 0 9.2± 71.3)U/L ,男性睾丸体积由 (4.5± 1.7)ml增至 (5 .3± 0 .8)ml。骨龄由 (5 .5± 3.1)年增至 (5 .9± 3.0 )年 ,体质量无明显变化。 18例出现亚临床甲减。结论　国产rhGH是治疗GHD安全、有效的药物     

Chronic growth retardation with normal growth hormone response to provocative stimuli and low somatomedin activity. Long-term therapy with human growth hormone

Four prepubertal children with chronic growth retardation (growth velocities less than or equal to 4 cm/yr), normal growth hormone (GH) response to provocative stimuli and low basal but increased somatomedin activity values after GH administration, received continuous GH-therapy (4 IU/three times a week) for an 18-24-month period. Growth velocity doubled during the first 12 months of therapy and remained 4-6 cm/yr until the end. Bone age progressed according to chronological age and adult height predictions improved. No thyroid function or carbohydrate and lipid metabolism anomalies were observed. After completion of this GH-therapy period, patients remained off treatment during the following six months. Growth velocities were similar to pre-GH-treatment values in two patients, lower in the third and higher in the fourth, who was by then pubertal. Thus, in these patients, long-term GH-therapy promoted growth and improved adult height prediction.