Growth hormone secretion in patients with constitutional delay of growth and pubertal development

Growth hormone levels were measured every 30 minutes during sleep over 9 hours in 20 prepubertal patients with constitutional delay of growth and puberty (CGD) and in 10 age-matched controls, all of whom had had normal GH responses to an orally administered dose of clonidine. We found no significant difference in the mean 9-hour overnight GH concentration between groups (4.5 +/- 1.8 ng/ml (mean +/- SD) in the CGD group, 4.4 +/- 2.8 ng/ml in the control group). Total GH output (258 +/- 99 U vs 222 +/- 135 U), total number of nocturnal GH pulses (3.6 +/- 0.8 vs 3.3 +/- 1.3), mean peak GH response during nocturnal sampling (13 +/- 1.2 ng/ml vs 13.2 +/- 1.3 ng/ml), and basal somatomedin C concentrations were not different in the children with growth delay and controls. We conclude that prepubertal patients with constitutional delay of growth and puberty secrete GH normally and do not seem to have any abnormality in GH regulation.     

Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal maturation during GH therapy

We report four patients (three male, one female) with septo-optic dysplasia and growth hormone deficiency. All had GH therapy for a period of four to eight years until reaching final height. In all four cases bone maturation during puberty was accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was clearly below the predicted height. The progress of pubertal stages was very short in all patients. In three patients TSH and prolactin release after TRH stimulation were increased. These data support a hypothalamic original of the endocrine disorder. Insufficient GH release, even after repeated GHRH stimulation, is in contrast to this assumption. In one case there was a late manifestation of neurohormonal diabetes insipidus, which indicates the possibility of later disease progression. MR imaging of the brain demonstrated variable malformation of the septum pellucidum, chiasma and nervus opticus or the pituitary gland, respectively.     

Effects of testosterone therapy for pubertal delay

We reviewed the effects of a brief course of testosterone enanthate (four intramuscular injections of 200 mg at three-week intervals) on pubertal advancement and final adult height in 50 male patients with delayed puberty. Although those treated with testosterone were slightly older than a group of 38 untreated subjects, the two groups had similar baseline mean bone age delays, height z scores, Tanner stages, predicted adult heights, growth rates, and midparental heights. Four months after baseline, the treated group had a significantly greater mean increase in the height z score and sexual maturation index. At 12 months, the mean increase in the sexual maturation index remained greater in the treated group. Among treated and untreated subjects older than 17 years, there was no significant difference in the absolute height z score. Over 95% of treated subjects were satisfied with the effects of therapy.     

Growth pattern and skeletal maturation following growth hormone therapy in growth hormone deficiency: factors influencing outcome

OBJECTIVE: To evaluate pattern of growth and skeletal maturation following growth hormone (GH) therapy in children with GH deficiency (GHD) with special emphasis on factors influencing outcome. METHODS: Records of ninety-six children (67 boys, 29 girls) with GHD treated with GH for 2.3 +/-2.1 years were reviewed. RESULTS: Height SDS at the end of treatment was significantly higher than that at initiation (-3.4 +/- 1.7 versus -4.8 +/-1.6, P < 0.001); it was however lower than target height SDS (corrected height SDS (1.8 +/- 1.6, P < 0.001). The greatest increase in height SDS was observed during the first two years of treatment. Kaplan Meier survival analysis showed that 92%; of all subjects achieving end height SDS in the target height range did so within the first two years of treatment. Height SDS for bone age increased by 0.7 +/-0.9 during treatment (from -2.5 +/- 1.0 to -1.8 +/- 1.5, P < 0.001); the increase was however lower compared to that for height SDS for chronological age (P < 0.01) suggesting inadvertent skeletal maturation. End height SDS was influenced by duration of treatment and corrected height SDS on multivariate analysis. CONCLUSION: GH treatment improves growth parameters in GHD; height however still remains compromised. Most of the catch-up growth occurs within two years of treatment emphasizing the need of optimal treatment during this period. Inadvertent skeletal maturation during treatment indicates a need for evaluating the role of agents effective in retarding skeletal maturation.     

TSH secretory pattern and thyroid function in children with growth hormone neurosecretory dysfunction

We evaluated the TSH secretory pattern and free T4 in 10 prepubertal children with short stature, normal response to GH provocative tests, and reduced GH integrated concentration (IC-GH) (GH neurosecretory dysfunction). Although their nadir TSH, peak TSH, TSH surge, and free T4 were lower than those of 12 children with short stature and normal IC-GH, none of the differences reached statistical significance. Thus, our results suggest that children with low IC-GH (GH neurosecretory dysfunction) exhibit a TSH secretory pattern and thyroid function similar to those with normal IC-GH.     

Constitutional delay of growth: expected versus final adult height

Constitutional delay of growth and puberty is believed to represent a variation of normal growth, and it is expected that children with this condition will grow for a longer duration than average and reach a height that is normal for their genetic potential. The records of children with constitutional delay of growth and puberty who were initially seen in the Pediatric Endocrine Clinic at the Oregon Health Sciences University between 1975 and 1983 were retrospectively reviewed. Criteria for study included a height more than 2 SD below the mean, a significantly delayed bone age, and a normal growth velocity on follow-up. Forty-two subjects were located and final adult height measurements were obtained. AT contact, the 29 male subjects (mean age = 23.9 years) were 169.5 +/- 4.5 cm tall (mean +/- SD), and the 13 female subjects (mean age = 20.5 years) were 156 +/- 3.8 cm tall. Adult height predictions during follow-up, using either the Bayley-Pinneau or Roche-Wainer-Thissen method, were close to final adult heights. The males were 1.2 SD and the females 1.3 SD below the 50th percentile as adults. This finding was not fully explained by genetic short stature; the males fell 5.1 cm and the females 5.3 cm below target heights based on midparental heights. It is concluded that this discrepancy is most likely explained by a selection bias of the shortest children referred to and observed in a subspecialty clinic, although a defect in human growth hormone secretion or function in children at the far end of the spectrum of constitutional delay of growth and puberty cannot be excluded.     

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     

Constitutional delay of growth and puberty: from presentation to final height

This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP.     

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.     

Final height and pubertal development in 55 children with idiopathic growth hormone deficiency,treated for between 2 and 15 years with human growth hormone

Sixty patients with the diagnosis of idiopathic growth hormone deficiency have been followed till final height was reached, after hGH treatment lasting between 2 and 15 (average 5.4) years. Twenty-six had total and 13 partial isolated growth hormone deficiency (IGHD); 10 had GHD plus gonadotrophin deficiency (GnD); six had multiple pituitary hormone deficiency (MPHD) and five, labelled transient prepubertal GHD, had normal responses in the insulin tolerance test when retested after the end of treatment.The final height of the patients with IGHD averaged 2.3 SD below the population mean, or 2.0SD below their midparent mean. Half the boys, but only 15% of the girls, ended above the population 3rd centile. There was no difference in final height between those with total and partial deficiency nor between patients treated prepubertally and those in whom treatment started in early puberty. In the 39 patients with IGHD the correlation of final height with midparent height was 0.72, a figure identical to that occurring in the normal population. Though final height was chiefly influenced by parental height, it was also affected by the degree of smallness when treatment began being lowered by an average of 2.5 cm for every SD that the patient's height at beginning of treatment lay below the average of all IGHD children, parents' heights being allowed for.Since untreated patients end at about 6 SD below the mean, treatment during the age span represented in these patients recovered 4SD, but failed to recover the remainder. The lost 2 SD may be due to the late start of treatment (averaging 11 years of age even in our prepubertal patients). Our findings emphasise the importance of early diagnosis, so that future patients never drop to 4 or 5 SD below mean height for age, but only to 2 or 3.Patients with IGHD plus GnD had final heights averaging 1.5 SD below the population mean and those with MPHD 1.0 SD below. This was entirely due to their developing longer legs than the patients with IGHD, the final sitting heights being the same. The long legs were due to treatment with sex steroids being started relatively late. Patients with IGHD who entered puberty spontaneously did so late in time and in the boys pubertal development was normal. In the girls there was a disturbance in the normal relationship of pubertal events and in two menarche never occurred.     

小于胎龄儿生后生长发育和激素水平研究

小于胎龄儿 (smallforgestationalage ,SGA)是指出生体重在同胎龄平均体重的第 10百分位以下或低于平均体重 2s的新生儿。国外报道其发生率为 5 % ,在我国发病率约为5 %～ 15 % ,生后常有体格发育落后。一般认为SGA生后发生身材矮小的风险为出生身材正常儿的 5～ 7倍。SGA的本质是宫内生长迟缓 ,内分泌轴形成过程受到影响。有关SGA在胎儿期和新生儿期相关激素的研究已有报道 ,但对SGA生后生长落后与生长激素、胰岛素生长因子 1、胰岛素生长因子结合蛋白 3和瘦素等关系的研究相对较少。本文就此作一简要综述。一、SGA生后生长发育根…     

广州女孩青春期发育模式的纵向研究

目的 纵向追踪广州女生性征发育和体格生长,了解青春发育模式及特点.方法 对广州市东、西、中部4所小学1992-2001年311名小学女生自一年级[(7.24±0.38)岁]起至其达到成年身高[238名,(15.72±0.84)岁],每年1次测量其身高、体重;并从三年级起至六年级,检查性征和询问初潮.分析乳房、阴毛发育、初潮、身高线性突增达峰速度(PHV)年龄、成年身高(FAH)及彼此间的关系.结果 (1)乳房发育达到B2期的年龄为9.83(9.33～10.33)岁,阴毛发育达到阴毛2期的年龄10.67(9.92～11.38)岁,初潮年龄(12.35±1.30)岁,均迟于2003年全国横向调查中广州地区女孩的调查结果.PHV年龄(10.52±1.07)岁.B2至PHV为1.00(0.50～1.50)年,B2至初潮为2.92(2.08～3.67)年,乳房发育达到B2期至FAH为(4.80～0.85)年.(2)FAH为(158.74±5.74)cm,高于1985年而低于2003年广州地区横向调查结果.(3)乳房发育达到B2期的年龄是初潮年龄的独立相关因素.(4)乳房发育每期持续年限、B2至PHV及B2至初潮间隔年限,与英国(1969年)、塞内加尔(1995-2000年)、美国(1986-1996年)的纵向调查结果相近.结论 近20年广州女生青春发育呈提前趋势,但成年身高却有增加;青春发育进展模式与世界各国历年调查结果相近.     

Letrozole significantly improves growth potential in a pubertal boy with growth hormone deficiency

Clinical experience with using an aromatase inhibitor to suppress estrogen production during puberty for improvement of growth potential in adolescents with short stature is limited. This report documents treatment of such a patient with a combination of growth hormone and letrozole, a third-generation aromatase inhibitor. Our case demonstrates a favorable outcome on a short-term basis.