Update on the Kabi International Growth Study, April 1989

International Board, Kahi International Growth Study (Kahi, Stockholm, Sweden). Update on the Kahi International Growth Study, April 1989. Acta Paediatr Scand [Supp] 356: 173, 1989.
The efficacy and safety of recombinant human growth hormone (rhGH) treatment is under prospective evaluation in children with various short stature conditions. Of the 987 children enrolled up to April 1989, 836 (84.7%) had classic growth hormone deficiency (GHD) and 151 (15.3%) non-GHD. There was a predominance of idiopathic growth hormone deficiency (IGHD), with a ratio of IGHD to secondary or organic GHD (OGHD) of 2.2:l. There were more boys than girls in both the IGHD and OGHD groups. Isolated GHD was more common than multiple pituitary hormone deficiency except in some of the groups with OGHD. About half of the OGHD patients had GHD secondary to treatment for CNS tumours. Idiopathic short stature and Turner's syndrome were the most common diagnoses in the non-GHD group. The median age at onset of treatment in IGHD was 8.2 years for boys and 8.6 years for girls. The corresponding figures for OGHD were 14.0 years and 12.2 years, respectively. The height SDS for chronological age at the start of treatment was -3.0 for IGHD and slightly less for children with OGHD. Approximately one-third of the children had already reached puberty at the start of hGH treatment.     

Causes of short stature in children in relation to their midparental height

Introduction: It is considered that the evaluation of a child's height strongly depends on the evaluation of his/her midparental height. Aim of study: Analysis of causes of short stature in children in relation to midparental height. Material and methods: The study included 452 children with short stature, aged 3-18 yrs. The group of children included 178 girls and 274 boys. The children's measurements were standardized using the arithmetic mean and standard deviation for the Institute of Mother and Child norms. Midparental height was evaluated according to standards for 18-year-olds. The average height deficit was -2.5 SDS±0.65. The average midparental height was 166.07 cm±4,63 and in SDS it was -0.93±0,74. Results: Growth hormone deficiency (GHD) or multihormonal pituitary deficiency was found in 34.3% of the patients (50 girls and 105 boys). In 22 girls (12.48) the Turner syndrome (TS) was diagnosed. Other causes of short stature were observed in 37 children. No hormonal disorders were found in the remaining group (275 children). 7% of those children were characterized by significant height deficit (-3 SDS). The difference between midparental height of GHD children and healthy children was not statistically significant. Body height of 20% of GHD children was consistent with their midparental height. The midparental height of girls with TS was significantly higher than the midparental height of the other children. The body height of 50% of girls with TS differed from their midparental height. The body height of 40% of healthy short children was consistent with their midparental height. Conclusions: 1. Children with short stature are a very heterogenous group of patients. 2. Comprehensive evaluation of physical development in children should not be restricted to the widely used criterion of midparental height.     

Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency

In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD score (SDS) increased throughout the three-year GH treatment period. The overall mean height SDS increased from –3.5 at baseline to –2.5 after 3 yr of treatment. The mean change in height SDS during these 3 yr was 1.1. In addition, height assessment of SD score based on Down syndrome-specific growth data in the Japanese population revealed that the height SDS (Down syndrome) also increased across the 3-yr GH treatment period. The mean change in height SDS (Down syndrome) during these three years was 1.3. GH therapy was effective for Down syndrome short stature accompanied by GHD, and no new safety concerns were found in this study.     

Psychological findings in children with short stature

AIM: The aim of this study is to evaluate the psychological findings in patients with short stature. METHODS: We studied 19 subjects, 13 males and 6 females, with age range 7-14 years. We evaluated heigth, growth velocity, bone age, target height and growth hormone secretion after provocative stimuli. Psychological evaluation included: Kovacs Scale, Children's Depression Inventory (CDI), Anxiety Scale (Busnelli-Dall'Aglio-Farina); drawing of the human figure (Goodenough Test); Raven Test for neuropsychological performances (P.M. 38 and 47). Statistical analysis was performed using Mann-Whitney U-test. RESULTS: We diagnosed familial short stature (FSS) in 7 patients and growth hormone deficit (GHD) in 12. No statistical difference was found in the anxiety and depression tests, although the score was higher in GHD patients. The human figure drawing and the interview revealed low self-esteem, sense of inadequacy, dependence from parents, social inhibition in all patients. These characteristics were more evident in patients with GHD. Neuropsycho-logical evaluation by Raven test showed normal score in all patients, however subjects with FSS exhibited a higher score than with GHD (p<0.05). CONCLUSIONS: Our data suggest a negative influence of short stature on the affective field of children with short stature; GHD patients exhibited lower neuropsychological performances and more psychological problems than patients with FSS.     

Frequent growth disorders in puberty and adolescence

About 50% of our patients with concern about their actual or final height are adolescents (girls greater than 11 years, boys greater than 13 years). Growth data of 103 adolescent patients (70 boys, 33 girls) seen in 1988/89 are analysed. 85% of the patients (90% of the boys) complained of short stature (length less than 3rd centile) whereas tall stature (height greater than 97th centile) was more frequently concerning girls (9 out of 16 patients). Genetic short stature and constitutional delay of growth and adolescence (CDGA) were most often diagnosed in short stature patients. When retardation of physical maturation is a major concern in patients with CDGA, treatment with a low dose of sex steroids leads to an acceleration of growth and pubertal development. This advancement of maturation is important for reducing the psychosocial difficulties of the concerned adolescents. Constitutional tall stature was the most frequent diagnosis in our tall adolescent patients. If predicted final height is above 185 cm for girls or 200 cm for boys the administration of height dose sex steroids (ethinylo-estraidol or conjugated oestrogen for girls, testosteron for boys) for height reduction can be tried, since a reduction in height between 3.5 cm and 7.9 cm has been reported for girls and similar data exists for boys. Nevertheless a cautious approach must be advocated for the administration of oestrogens because possible long term hazards can not yet be excluded.     

The role of insulin like growth factor (IGF) — 1 and IGF — binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children

Objective  The purpose of this study was to evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. Methods  In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003–2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < −2, with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under −2 standard deviation. Results  Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 ± 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. Conclusion  No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor.     

Does constitutional delayed puberty cause segmental disproportion and short stature?

We have reviewed the growth of 98 boys and 34 girls with constitutional delay of growth and puberty followed until final height. At presentation chronological age was 14.1 (1.3) years (SD) in the boys and 13.0 (1.3) years in the girls. At presentation all patients were either prepubertal or in early pubertal maturation (4 ml testicular volume in the boys and breast stage II in the girls). Twenty-nine boys (30%) and 2 girls (6%) were treated with either sex or anabolic steroids. Mean height SDS in the boys at presentation was –2.7 (0.7) which rose to –1.9 (0.9) at final height attainment. This was significantly lower than the predicted final height SDS of –1.4 (0.8) and mid-parental height SDS of –0.5 (0.7). Similar results were obtained for the girls with a height SDS at presentation of –3.2 (0.8) which increased to –2.3 (0.7) at final height which was significantly lower than predicted final height SDS of –1.7 (0.6) and mid-parental height SDS of –0.8 (0.8). Both sexes had a relatively short sitting height at presentation; sitting height SDS –3.4 (1.0) and subischial leg length SDS –2.2 (1.0) in the boys and sitting height SDS –3.6 (1.1) and subischial leg length SDS –2.5 (0.7) in the girls. The relative disproportion between the segments had no significant change at final height. We are unable to explain the failure to achieve final height potential and the relatively disproportionate stature. Our data suggest that the late timing of the onset of puberty may be deleterious to spinal growth and consequently final height. The relatively short spinal length at presentation of constitutional delay of growth and puberty does not correct at the attainment of final stature.     

The causes of short stature in children in ambulatory care

The data relating to all children referred over a 10-year period to the out-patient department of a children's hospital in a West German city because of growth retardation were retrospectively analyzed. A diagnosis of short stature was made in 306 patients. The proportion of boys to girls was 2.5:1. The average age of the patients was about 10 years (0.75-17.4); 9.8% of the children were less than 4 years old, and 5.9% were over 16 years. In 68.3% of the patients the Study revealed constitutional delay of growth or familial short stature or a combination of two. Twelve children (3.9%) were demonstrated to have growth hormone deficiency.     

不同病因矮身材儿童TW2-R、C、T骨龄评分特征研究

目的　探讨不同病因矮身材儿童TW2-R、C、T骨龄评分特征, 为矮身材的病因诊断提供参考。方法　以363例未经治疗的矮身材儿童为研究对象, 根据病因分为4组：生长激素缺乏症(GHD, 27例)、特发性矮小(ISS, 280例)、小于胎龄儿(SGA, 41例)、Turner综合征(TS, 15例)。拍摄左手腕骨骨龄片, 应用TW-2骨龄评分法对各组患儿R骨龄、C骨龄及T骨龄进行评分, 将各序列骨龄与年龄对比分析。结果　GHD组男、女儿童表现为R骨龄、C骨龄及T骨龄均较年龄落后2岁以上。ISS组男童R骨龄、C骨龄及T骨龄较年龄落后约1岁; ISS组女童各序列骨龄与年龄比较无显著差异。SGA组男女儿童各序列骨龄与年龄比较无显著差异。TS组R骨龄及T骨龄较年龄显著落后, C骨龄与年龄比较无显著差异。结论 不同病因所致的矮身材儿童具有不同的TW-2 R、C、T各序列骨龄特点。TW-2 R、C、T各序列骨龄的评估对于矮身材儿童病因的诊断具有辅助作用。     

Final height in Swedish children with idiopathic growth hormone deficiency enrolled in KIGS treated optimally with growth hormone

Aim: To assess final height in children with growth hormone deficiency (GHD) treated with human recombinant growth hormone (GH). Methods: Final height data for 401 Swedish children with idiopathic GHD and treated with GH, included in KIGS (Pfizer International Growth Database) between 1987 and spring 2006, were analysed retrospectively. Data were grouped according to sex, age and severity of GHD. Height at entry into KIGS, at the onset of puberty and near final height were analysed between groups. Results: Groups were heterogeneous for GHD, which ranged from partial to severe. For all groups, mean final height corrected for mid‐parental height was within the normal Swedish height range. In patients with severe GHD, mean final height was almost identical to mean normal Swedish height. About 16% of patients showed disproportionality (short legs) at final height and were significantly shorter than other patients. The parents of these children also demonstrated short stature. Conclusion: Children with idiopathic GHD receiving GH replacement therapy can achieve a final height that as a group is within the normal range and all achieve a height within their genetic potential.     

An auxology-based growth hormone program: update on the Australian experience

In 1988, new guidelines for growth hormone (GH) usage emphasizing auxological criteria were adopted in Australia. Currently, 1,250 children with the following diagnoses are being treated: idiopathic GH deficiency (IGHD), 23.4%; malignancy-related GHD, 7.9%; Turner's syndrome, 12.1%; nonendocrine disorders, 22.2%; idiopathic short stature, 26.0%; endocrine disorders, 3.2%; unknown, 5.3%. At onset of GH therapy, mean age remained lowest in patients with IGHD (8.6 years); mean height SDS was unchanged over time in all groups (-2.8 to -3.3); mean GH doses were lowest for patients with idiopathic and malignancy-related GHD (0.15-0.16 mg/kg/week) and highest for the Turner's syndrome group (0.22 mg/kg/week). Children with GHD demonstrated the best final height outcome (mean final height SDS -1.0 +/- 1.1 for boys and -1.4 +/- 1.2 for girls; improvements of 2.0 SDS for both genders). Mean final height SDS for the other etiologies were similar: -2 in malignancy-related GHD (no improvement), -2.3 in nonendocrine disorders (improvement of 0.7), -1.8 in idiopathic short stature (improvement of 1.1), and -2.3 for Turner's syndrome (improvement of 0.9). In 1993-94, when more stringent entry and exit criteria were introduced, patient numbers and expenditure were halved and have remained unchanged (US dollars 9-10 M per year). The use of auxology-based criteria continues to make possible rational, effective, and economical use of GH therapy in short children in Australia.     

The diagnostic work up of growth failure in secondary health care; An evaluation of consensus guidelines

Background

As abnormal growth might be the first manifestation of undetected diseases, it is important to have accurate referral criteria and a proper diagnostic work-up. In the present paper we evaluate the diagnostic work-up in secondary health care according to existing consensus guidelines and study the frequency of underlying medical disorders.

Methods

Data on growth and additional diagnostic procedures were collected from medical records of new patients referred for short stature to the outpatient clinics of the general paediatric departments of two hospitals (Erasmus MC – Sophia Children's Hospital, Rotterdam and Spaarne Hospital, Haarlem) between January 1998 and December 2002. As the Dutch Consensus Guideline (DCG) is the only guideline addressing referral criteria as well as diagnostic work-up, the analyses were based on its seven auxological referral criteria to determine the characteristics of children who are incorrectly referred and the adequacy of workup of those who are referred.

Results

Twenty four percent of children older than 3 years were inappropriately referred (NCR). Of the correctly referred children 74–88% were short corrected for parental height, 40–61% had a height SDS <-2.5 and 21% showed height deflection (Δ HSDS < -0.25/yr or Δ HSDS < -1). In none of the children a complete detailed routine diagnostic work up was performed and in more than 30% no routine laboratory examination was done at all. Pathologic causes of short stature were found in 27 children (5%).

Conclusion

Existing guidelines for workup of children with suspected growth failure are poorly implemented. Although poorly implemented the DCG detects at least 5% pathologic causes of growth failure in children referred for short stature. New guidelines for referral are required with a better sensitivity and specificity, wherein distance to target height should get more attention. The general diagnostic work up for short stature should include testing for celiac disease in all children and for Turner syndrome in girls.     

Acid-base homeostasis in children with growth hormone deficiency

BACKGROUND: Although the primary use of growth hormone (GH) is to promote linear growth, it is also known to affect many metabolic processes and to influence renal function. In laboratory animals, growth hormone deficiency (GHD) causes a mild metabolic acidosis that is corrected by GH treatment. We observed a patient with GHD who initially presented with acidosis of unclear etiology and corrected the acidosis with GH treatment. OBJECTIVES: To determine: 1) whether children with GHD have lower mean serum bicarbonate concentrations than do children with short stature because of other causes; and 2) whether the presence of a low serum bicarbonate concentration increases the probability of GHD among children with short stature. METHODS: We collected data from the medical records of 143 children with short stature who had serum electrolyte concentrations measured as part of their initial evaluations, 66 with GHD and 77 with short stature as a result of other causes. We compared mean serum bicarbonate concentrations and bicarbonate standard deviation scores (SDS) between these two groups and determined the probability of GHD for patients according to bicarbonate SDS. RESULTS: The mean serum bicarbonate concentration was significantly lower in patients with GHD (mean standard deviation [SD]; 23.9 [0.4] mEq/L vs 25.2 [0.3] mEq/L) as was the bicarbonate SDS (-0.12 [0.14] SD vs 0.38 [0.10] SD). Twelve (75%) of 16 patients with bicarbonate SDS 1 SD. Patients with bicarbonate SDS between -1 SD and 1 SD had an intermediate probability of GHD, 46/102 (45%), similar to the overall prevalence of GHD in the study population (46%). Mean bicarbonate concentrations and bicarbonate SDS increased significantly in 9 patients who had repeat electrolyte measurements during treatment with GH (mean bicarbonate; 21.7 [1.1] mEq/L vs 26.9 [0.59] mEq/L, mean bicarbonate SDS; -1.24 [0.43] SD vs 0.55 [0.27] SD). CONCLUSIONS: Serum bicarbonate concentrations are lower in patients with GHD than in patients with short stature as a result of other causes. In addition, serum bicarbonate concentrations rise with GH treatment in patients with GHD. The probability of GHD is increased for patients with bicarbonate SDS 1 SD. These findings indicate a role for GH in maintaining normal acid-base homeostasis and suggest that GHD should be considered in children whose growth failure is attributed to other causes of acidosis.     

Physiological Growth Hormone Secretion and Response to Growth Hormone Treatment in Children with Short Stature and Intrauterine Growth Retardation

Stanhope, R., Ackland, F., Hamill, G., Clayton, J., Jones, J. and Preece, M.A. (Department of Growth and Development, Institute of Child Health, London and Serono Laboratories, UK). Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 47, 1989.
Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of < 20 mU/I during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m²/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from - 0.61 to +1.09, and the group treated with 30 U/m²/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.     

New reference for the age at childhood onset of growth and secular trend in the timing of puberty in Swedish

The objectives of the present work were to present a new reference for the age at childhood onset of growth and to investigate the secular trend in the timing of puberty in a community‐based normal population in Sweden. A total of 2432 children with longitudinal length/height data from birth to adulthood were used to determine the two measures by visual inspection of the measured attained length/height and the change in growth velocity displayed on a computer‐generated infancy‐childhood‐puberty (ICP) based growth chart. The series represents a sample of normal full‐term children born around 1974 in Göteborg, Sweden. We found about 10% of children were delayed (>12 mo of age) in the childhood onset of growth based on the previous reported normal range, i.e. 14% in boys and 8% in girls. Distribution of the age at childhood onset of growth was skewed. The medians were 10 and 9 mo for boys and girls, respectively. After natural logarithmic transformation, the mean and standard deviation (SD) were 2.29 (anti‐log 9.9 mo) and 0.226 for boys, 2.23 (anti‐log 9.3 mo) and 0.220 for girls, respectively. The 95% normal ranges were 6.3‐15.4 and 6.0‐14.3 for boys and girls, respectively. The distribution of the timing of PHV was close to the normal distribution. The mean values were 13.5 y for boys and 11.6 y for girls with 1 y SD for both sexes. Conclusion: A downward secular trend in the onset of puberty was clearly shown in the population. The age at childhood onset of growth did not correlate with the timing of puberty (r=?0.01 and 0.05, p > 0.7 and 0.1 in boys and girls, respectively). Normal ranges of the age at childhood onset of growth are in need of revise, as this study indicates. The new reference presented here could be a reliable indicator in further studies.     

Twelve-hour spontaneous nocturnal growth hormone secretion in growth retarded patients

Twelve-hour nocturnal GH secretion was studied in 30 children with familial short stature (FSS), constitutional growth delay (CGD), total growth hormone deficiency (TGHD), partial growth hormone deficiency (PGHD), or idiopathic short stature (ISS). No difference was observed between subjects with FSS and children with CGD. The mean 12-hour serum GH concentration was significantly lower in patients with TGHD (p less than 0.001), children with PGHD (p less than 0.01), and subjects with ISS (p less than 0.01) than in subjects with FSS and CGD. No overlap was observed between the range of mean concentration values of children with TGHD and that of subjects with FSS. A significant correlation was found between growth velocity expressed as SD from the mean for bone age and GH concentration (p less than 0.001). All patients with a growth velocity less than 3rd percentile for bone age showed a mean nocturnal concentration less than 4 ng/ml. These data suggest that evaluation of 12-hour spontaneous nocturnal GH secretion with GH sampling every 30 minutes can be usefully employed in the diagnosis of GH deficiency.     

Etiological profile of short stature

Objective : To study the frequency of various causes of short stature and their etiological contribution in a referral endocrinology and metabolism clinic at a tertiary care hospital.Methods : 352 children with growth retardation attending endocrine clinic between Feb 1999 to Mar 2001 were investigated for etiology of short stature. Agrawal’s growth chart was used for percentiles and height velocity. Various relevant radiological, biochemical and hormonal investigations were performed.Results : Normal variant short stature was the most common cause of short stature followed by endocrine causes.Conclusion : In males most common cause of short stature was constitutional growth delay, while in females most common cause of short stature was familial short stature.     

An Overview of the Diagnoses in the Kabi Pharmacia International Growth Study

This paper provides an overview of the diagnoses of patients entered in the Kabi Pharmacia International Growth Study (KIGS). By May 1991, data from a total of 5377 children treated with growth hormone (GH) were included in the main database. Of these children, 2691 were classified as having idiopathic GH deficiency (GHD), 866 as having GHD of known origin, and 1820 as having other causes of short stature. The majority of patients with idiopathic GHD have no history of perinatal trauma. In the patients with GHD of known origin, 137 were congenital cases and 729 acquired GHD. The largest number of congenital cases (114) belonged to the group of central malformations (e.g. septo-optic dysplasia and empty sella syndrome). Of the cases with acquired GHD, 73% were associated with tumours or leukaemia. Other causes of short stature include 12 groups of diagnoses, with more than 150 cases in four of them (idiopathic short stature, 635; defined syndromes with chromosomal aberrations, 337, of which 304 were Turner's syndrome; defined syndromes without chromosomal aberrations, 157; intrauterine growth retardation without stigmata, 366). Analysis of the KIGS data allows modern GH therapy for GHD to be compared with older treatment modalities. The study offers the advantage of larger numbers of cases than can be achieved in individual trials and allows assessment of the use of GH therapy for GHD of comparatively uncommon causes.     

儿童身材矮小的病因分析及遗传学诊断

目的 探讨身材矮小患儿的病因分布及遗传学诊断。方法 回顾性分析86例身材矮小患儿的病因分布及临床特征。结果 86例身材矮小患儿中,病因有6种,以特发性矮小症（ISS,41%）和生长激素缺乏症（GHD,29%）最常见,遗传性疾病（14%）次之。将遗传性疾病组与ISS组、GHD组比较显示,各组患儿就诊年龄、身高、出生身长、出生体重、父母身高及胰岛素样生长因子1（IGF-1）水平差异均无统计学意义（P > 0.05）,但遗传性疾病组身高距同年龄同性别个体身高第3百分位数的差值（ΔP3）和身高标准差评分（HtSDS）显著低于ISS组（P < 0.05）,但与GHD组相比差异无统计学意义（P > 0.05）。对遗传性疾病组患儿的临床表现进行分析,显示不同遗传性疾病表型谱存在异质性及表型重叠性。结论 ISS、GHD和遗传性疾病是儿童身材矮小的主要病因。对存在严重身材矮小的患儿,在除外GHD外,有必要进一步行遗传学检查明确诊断。     

Management of Growth Hormone Deficiency Through Puberty

ABSTRACT. As a model of the growth hormone (GH) dependence of growth in prepuberty and puberty, the growth of 182 children (93 boys, 89 girls) who survived in first remission for treatment of acute lymphoblastic leukaemia was examined. Chemotherapy regimens, including intrathecal methotrexate, were similar in all patients, but CNS treatment differed, in that one group received 2400 cGy cranial irradiation, while the other received 1800 cGy. There was a significant decrease in height SDS during prepuberty, which was equivalent in both sexes, whereas there was a much greater decrease in pubertal growth in girls than in boys. Girls treated with the lower dose regimen of cranial irradiation had their onset of pubertal maturation significantly advanced, to a mean of 9.9 years ( p < 0.001). Previous studies have indicated that the duration of puberty is shortened by GH treatment in patients with idiopathic multiple pituitary hormone deficiency or isolated GH deficiency (GHD). To determine whether an increase in the dose of GH administered during the adolescent growth spurt would improve final height, a prospective randomized trial was performed in 32 children (25 boys, 7 girls) with isolated GHD treated with a GH dose regimen of 15 IU/m²/week as daily s.c. injections. At the onset of the pubertal growth spurt, the patients were randomized either to an unchanged dose or to 30 IU/m²/week. There was no significant change in height velocity with the doubled dose of GH, but there was a trend in the advancement of pubertal maturation which was considered to be dose related. It is suggested that these findings are of relevance to the treatment of GHD in puberty, especially in girls with early or precocious puberty occurring as a consequence of low-dose cranial irradiation. It is concluded that optimum final heights may not be achieved in these patients without the therapeutic manipulation of the onset and/or duration of puberty.