Growth response to growth-hormone administration during the decelerating phase of the pubertal growth spurt in short normal children

In order to investigate the value of growth hormone (GH) treatment during late puberty, we studied the effect of human GH (hGH) administration (0.85 +/- 0.30 IU/kg/week; range: 0.44-1.28) on height velocity (HV) after the peak of the pubertal growth spurt in a group of 10 (4 girls and 6 boys) short normal children (GH peak after pharmacological stimulation: 15.5 +/- 2.3 ng/ml) with growth retardation (height: 2.6 +/- 0.3 SD) and puberty Tanner stage 4. A group of 10 untreated children, observed prior to the study, served as controls. The children were regularly measured during their pubertal growth spurt, and HV (cm/year) was calculated every 6 months. The pretreatment evaluation consisted of 2 consecutive 6-month periods characterized by a decrease in HV of at least 25%. In the group of selected children, hGH administration was then initiated and growth variables were evaluated after 6 and 12 months of therapy. Skeletal maturation was evaluated at the beginning as well as after 6 months and 12 months of hGH therapy. In the controls, HV (mean +/- SD) had decreased from 8.8 +/- 1.8 to 4.9 +/- 1.4 cm/year during the pretreatment period (in girls from 7.9 +/- 1.4 to 4.1 +/- 0.6 cm/year and in boys from 9.6 +/- 1.6 to 5.8 +/- 1.2 cm/year). During the following semester, HV was 3.3 +/- 0.8 cm/year (girls: 3.4 +/- 1.0 and boys: 3.2 +/- 0.2 cm/year).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth in disorders of adrenal hyperfunction

Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.23 +/- 0.42 and 1.3 +/- 0.37 SDS respectively. In poorly controlled CAH, excess androgens cause early epiphyseal fusion and adult short stature. Increased growth occurs only after 18 months of age, even in untreated CAH, i.e. hydrocortisone >10 mg/m(2)/day is not generally required and may suppress infantile growth, affecting childhood and adult height. Growth was studied in 19 patients, aged 6.4-17.8 years, with Cushing's disease (CD). At diagnosis, mean height SDS was -1.81 (1.2 to -4.17), 53% < -1.8 SDS, height velocity in 6 was 0.9-3.8 cm/year and mean BMI SDS 2.29 (0.7-5.06). From 1983 to 2001, CD was cured in 18 patients (61%) by transsphenoidal surgery (TSS) alone and 39% by TSS plus pituitary irradiation (RT). In 13 patients, growth hormone (GH) was assessed by ITT/glucagons at 1-108 months after cure. Four had severe GH deficiency (<9 mU/l), 7 subnormal (10-29 mU/l) and 2 normal (>30 mU/l) GH status. Subnormal GH was present in 7 subjects >2 years after TSS or RT cure. In 10 subjects, aged 12.9 +/- 3.4 years, growth after cure was studied for 9.1 +/- 5.0 years. Nine had no catch-up growth in the interval of 0.3-1.1 years after cure (mean HV 5.3 +/- 2.4 cm/year). All these had GH deficiency peak GH 0.5-20.9 mU/l, and received hGH 2.7 mg/m(2)/week, 3 with GnRHa. All 10 showed long-term catch-up growth with mean delta SDS at diagnosis (Ht SDS-target Ht SDS) -1.72 +/- 1.26 improving to -0.83 +/- 1.08 (p = 0.0005) at latest of final Ht. At diagnosis, virilization was present in 82% of 17 patients with CD. Mean SDS values of serum androstenedione, DHEA-S and testosterone were normal, i.e. 0.72 (-2.9 to 3.0), -0.8 (6.0 to 2.2), 0.7 (-7.9 to 9.5) respectively, whereas SHBG was reduced at -2.1 (-5.3 to 1.2), increasing free androgen levels. Bone age (BA) was delayed (mean 1.46 years) in 14/16 patients, suggesting cortisol excess contributed more then androgen effect to skeletal maturation. In conclusion, most paediatric patients with CD had subnormal linear growth with delayed BA. After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height.     

Bromocriptine treatment in tall adolescents: two years of clinical experience

34 adolescents referred for excessive height prediction (HP) (11 boys with HP greater than 196 cm, 23 girls with HP greater than 180 cm) were treated for 9-15 months with bromocriptine (5-7.5 mg/day). Minor and transient side effects were observed in 20% of the subjects at the beginning of the treatment. Treatment had to be stopped in 1 boy complaining of asthenia and headache. Puberty developed normally, 19 girls experienced menarche during treatment and 1 continued regular menses. Bromocriptine treatment induced: (1) a significant decrease (p less than 0.001) in growth velocity from (mean +/- SEM) 8.6 +/- 0.4 to 5.3 +/- 1.5 cm/year in boys and from 7.1 +/- 0.2 to 4.6 +/- 0.6 cm/year in girls; (2) a twofold mean increase in skeletal maturation rate. Adult HP was reduced significantly from 202 +/- 1.4 to 195.4 +/- 1.2 cm in boys, and from 184 +/- 0.7 to 179.8 +/- 0.7 in girls. These results confirm our previous report suggesting that bromocriptine is a valuable alternative to sex steroid treatment in order to limit the final height in excessively tall adolescents.     

Short-term growth response to GH treatment and considerations upon the limits of short-term growth predictions

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.     

Final height attainment and gonadal function in girls with precocious puberty treated with cyproterone acetate.

Thirty-four girls with precocious puberty (27 idiopathic, 6 cerebral, 1 McCune-Albright syndrome) were treated with cyproterone acetate (CPA) for 1.2-8.4 years (3.71 +/- 0.31; mean +/- SEM) at a daily dosage of 66-150 mg/m2 (103.7 +/- 6.2). The mean chronological age (CA) and bone age at the beginning of treatment were 5.99 +/- 0.31 and 8.6 +/- 0.39 years, respectively, and 9.78 +/- 0.19 and 12.44 +/- 0.22 years, respectively, at the end of therapy. At the last evaluation, mean CA was 14.23 +/- 0.4 years, and 32 girls had reached final height. The control group consisted of 10 girls with idiopathic precocious puberty who, at their parents' request, were not treated. Mean CA at the onset of pubertal signs was 6.05 +/- 0.25 years. All patients had reached final height at the time of the last observation. There was no significant difference between final height of treated (152.43 +/- 1.36 cm) and untreated (149.55 +/- 1.99 cm) girls. Final height was significantly lower than target height in both treated (155.08 +/- 0.92 cm; p < 0.025) and untreated (156.45 +/- 1.29 cm; p < 0.0005) patients, but the mean height of treated patients is nearer to target height than that of untreated ones. A positive correlation was found between final height and target height both in treated (p < 0.005) and untreated (p < 0.05) patients. After the discontinuation of CPA treatment all girls resumed the progressive course of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)     

Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience

BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5-0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1 years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/- 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.     

Total pubertal growth and markers of puberty onset in adolescents with GHD: comparison between mathematical growth analysis and pubertal staging methods

Two methods of determining puberty onset (Preece- Baines model 1 (PB1) and Tanner staging) were used to calculate total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD). PATIENTS AND METHODS: 34 patients (11 girls) met the following inclusion criteria: isolated GHD, >2 years growth hormone therapy prior to puberty onset, regular weight-adjusted GH dosage, known final height (age >21 years or height velocity <0.5 cm/year), no induction of puberty. PB1 was used to define age and height at onset of the pubertal growth spurt ("take-off"). RESULTS: The results (mean +/- SD) were as follows: in girls, mean age at take-off was 9.8 years; 2.0 +/- 1.1 years before breast stage B2. In boys, mean age at take-off was 11.3 years; 1.4 +/- 0.8 years before testes volume >3 ml. Height at take-off was lower than at Tanner stage 2 by 12.4 +/- 7.6 cm in girls and 7.7 +/- 5.3 cm in boys. TPG was thus markedly greater (p < 0.001) using the PB1 method, as compared with Tanner stage2. Peak height velocity was normal. Final height was -0.5 +/- 0.7 SDS in females and -0.4 +/- 0.9 SDS in males. CONCLUSIONS: The method of measuring TPG from take-off is more objective, and has potentially greater implications for GH therapeutics than the Tanner stage method. In our study, 40% of TPG occurred before "breast stage B2" was attained in GHD girls; whereas 23% of TPG occurred before "testes >3 ml" in GHD boys.     

A survey on growth and sexual development of adolescent students in Changhua City: growth of body height and weight

In order to understand the physical growth and sexual development of contemporary adolescents, a cross-sectional survey was conducted during the period September 1983 to May 1984. The population came from all the pupils from 4th grade up, and all the junior and senior high students of Changhua City. By using stratified cluster sampling, 1419 boys and 1599 girls participated, ranging in age from 8 to 19 years. Body weight and height were measured. Growth spurt is a unique event during adolescence. It is well shown in the distance curves and pseudo-velocity curves of body height and weight. In boys, the growth spurt of height spanned from 12.0 to 14.8 years, with peak height velocity (PHV) at 13.5 years. In girls it was from 10.0 to 12.6 years and peaked at 11.5 years. The growth spurt of weight occurred from 12.0 to 15.9 years in boys with peak weight velocity (PWV) at 14.5 years, while girls had a growth spurt at 10.0-12.7 years with PWV at 11.5 years. Girls entered into the growth spurt about 2 years earlier, and also entered into PHV, PWV, two and three years earlier respectively than boys, while boys had a more intense and longer growth during the growth spurt than girls. Between 10.0-13.0 years girls were taller than boys, and between 12.0-13.0 years they were heavier than boys. However, from 13.5 years onward girls were soon surpassed by boys both in height and weight. Growth in height after 16.5 years in boys and after 15.5 in girls was minimal. Growth in weight in boys also became minimal after 16.5 years while girls weight even dropped a little bit after 16.5 years. At the mean age of 17.5 years, boys were 168.1 cm, girls were 156.2 cm in average, boys being 12 cm taller than girls after reaching their final height.     

Effect of growth hormone therapy on IGF-I, bone GLA-protein and bone mineral content in short children with and without chronic renal failure.

Chronic renal failure (CRF) in the young is complicated by, among other conditions, growth retardation, hyperparathyroidism and uremic osteodystrophy. Many children with CRF are now being treated with growth hormone (GH). Since GH has a direct mitogenic effect on osteoblasts in culture, we studied the effects of GH therapy on osteoblastic activity, such as serum alkaline phosphatase (AP), bone GLA-protein (BGP) and bone mass density (BMD) in poorly growing children with and without CRF. Fifteen (4 girls, 11 boys) healthy children with short stature (SS) and 10 (3 girls, 7 boys) children with end-stage renal failure (CRF) 4.5-12.4 years of age were treated with daily subcutaneous injections of GH in a dose of 0.1-0.125 IU/kg/day for 1 year. IGF-I, BGP and BMD of the spine were determined before and after the year of treatment. During GH therapy, a similar increase in height velocity and IGF-I were noted in SS and CRF groups: 3.8 +/- 0.77 to 8.38 +/- 1.25 (p < 0.001) vs. 4.0 +/- 0.6 to 7.14 +/- 1.3 cm/year (p < 0.001) and 7.8 +/- 2.6 to 21.8 +/- 7.5 (p < 0.01) vs. 7.9 +/- 1.3 to 21.5 +/- 5.6 nmol/l (p < 0.01), respectively. AP increased from 205 +/- 27 to 274 +/- 50 IU/l (p < 0.01) in the SS group but not in CRF patients (223 +/- 58 pre- 218 +/- 51 IU/l post-GH therapy).(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.     

Adrenal androgens in children with short stature

Recent data suggest that adolescent individuals with growth hormone (GH) deficiency have subnormal levels of adrenal androgens (AA). In order to determine the developmental pattern of AA in GH deficiency and to assess whether AA levels can help identify children with GH deficiency, we measured plasma concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and cortisol in the basal state and during prolonged adrenocorticotropin (ACTH) infusion (8 h) in a group of 34 individuals, 26 males and 8 females, with short stature. Their chronological ages (CA) ranged from 1.75 to 17.5 years (median 10.35 years). The subjects were grouped into two categories according to the results of pituitary testing: group 1 = short, non-GH-deficient (n = 16), and group 2 = GH-deficient, ACTH-sufficient (n = 18). Patients in groups 1 and 2 had similar bone ages (BA: 7.2 +/- 0.7 vs. 7.5 +/- 1.0 years) and Z scores for height (-3.0 +/- 0.2 vs. -3.2 +/- 0.3 units) and height velocity (-2.5 +/- 0.4 vs. -2.6 +/- 0.2 units). For both groups there were significant increases from basal to peak levels for DHEA, DHEA-S, delta 4A and cortisol following prolonged ACTH infusion. Although both basal and peak levels of DHEA-S overlapped in groups 1 and 2 for all CA and BA, levels in group 2 tended to be lower, especially for BA greater than 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of central precocious puberty with an LHRH agonist (Buserelin): effect on growth and bone maturation after three years of treatment

The LHRH analog Buserelin was used to treat 27 children (21 girls, 6 boys) with central precocious puberty. Nineteen patients had idiopathic precocious puberty and 8 had organic lesions (hamartoma, hydrocephalus or suprasellar arachnoid cyst). All patients received 20 or 30 micrograms/kg/day s.c. of Buserelin, and we obtained plasma E2 less than 20 pg/ml, vaginal maturation index less than 30 in girls or plasma testosterone less than 0.3 ng/ml in boys. The mean growth rate decreased from 9.3 +/- 0.5 to 4.6 +/- 1.3 cm/year after 3 years. The velocity of skeletal maturation decreased so that the final height prediction improved by a mean value of 1.6 SD. As the follow-up increases, this study confirms that LHRHa therapy is effective and potentially improves the final height of children presenting active and severe central precocious puberty.     

Association of pharmacological tests and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases

Growth hormone (GH) secretion can presently be investigated by several methods: pharmacological provocative tests, study of 24-h GH secretion, measurement of somatomedin-C (Sm-C)/insulin-like growth factor (IGF) I, and the growth hormone-releasing hormone (GHRH) test. In order to compare the results obtained, these methods were used in 257 children with growth retardation (169 boys, 88 girls). Their height SD was -2.7 +/- 0.2, chronological age 11 3/12 +/- 1 6/12 years, and bone age 8 4/12 +/- 1 4/12 years. Mean growth velocity was 4.5 +/- 1.5 cm/year. One hundred and thirty-eight boys and 80 girls were prepubertal, and 31 boys and 8 girls were pubertal (B2 G2). All children underwent the study of 24-h GH secretion (n = 257) and pharmacological provocative tests (two tests, n = 213; one test n = 44). Sm-C/IGF I was measured in prepubertal children (n = 131), and a GHRH test was carried out (n = 153). In addition, the mean integrated concentration of growth hormone secretion (IC-GH) was assessed in a control group of 23 children and was found to be 5.4 +/- 1.2 ng/ml/min. The IC-GH in the group as a whole was 2.6 ng/ml/min. The mean maximum peak during pharmacological tests varied considerably according to the test used, ranging from 7.8 ng/ml for the arginine test to 17.1 ng/ml for the glucagon and betaxolol test. The maximum peak and the 24-h IC-GH were not significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma dehydroepiandrosterone, its sulfate, testosterone and FSH during puberty of African children in Gabon

Plasma levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), testosterone (T) and follicle stimulating hormone (FSH) were measured by radioimmunoassay in 111 schoolboys and 95 schoolgirls from 7 to 18 years. 68 male and 55 female adults aged from 19 to 25 were also investigated. Results are expressed as the mean +/- SD, DHEA was the first hormone to vary showing a significant mean increase between the 10 and 11 year age groups of both boys and girls. Higher levels were observed in the age 12 group (boys 164.70 +/- 60.74; girls 256.60 +/- 145.40 ng/dl) but were followed by a significant decrease in both 13 year old groups. Similar increases followed by decreases were also noted for DHEAS, although the increase started between 11 and 12 years and reached a maximum at 13. An abrupt increase in FSH levels between 11 and 12 years followed by a plateau through 15-18 years, was observed for boys and girls. As expected, T levels increasing significantly in boys with the initial rise between 11 and 12 and a climb through to the 15-18 age group. Our results suggest a late plasma DHEAS secretion with adult levels attained after age 19. Menarche was also found to be late.     

Effect of gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty: final height results

OBJECTIVE: The small number of boys present in most studies on final height (FH) after gonadotropin-releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP) offers difficulties in the evaluation of the effects of treatment on FH in males. METHOD: We therefore combined FH data from The Netherlands, Italy and France to study the effect of GnRHa treatment in a large group of 26 boys with CPP. RESULTS: The mean chronological age at the start of treatment was 7.6 +/- 2.0 (SD) years, bone age (BA) was 11.0 +/- 2.1 years. All boys were treated with depot formulations of the GnRHa triptorelin with established gonadal suppression for a mean treatment period of 4.7 +/- 2.1 years. FH was 172.9 +/- 6.6 cm. FH standard deviation score (SDS) was -0.66 +/- 1.22, not significantly different from the target height SDS of -0.23 +/- 0.75. FH-SDS was significantly lower in the subgroup of 12 patients with organic CPP compared to patients with idiopathic CPP (-1.34 +/- 1.06 vs. -0.08 +/- 1.06, respectively; p = 0.01), but no difference in height gain was observed. The mean estimated height gain, defined as the difference between predicted and actual adult height was 6.2 +/- 8.7 cm using the average tables of Bayley and Pinneau, and 0.3 +/- 8.6 cm using the BA advance adjusted tables. Regional differences in height gain were observed between the different countries, reflecting different local practices. CONCLUSION: We conclude that GnRHa treatment in boys results in a FH close to target height.     

儿童身高生长追踪研究

以北京市106名儿童为样本 ,为研究各年龄生长速度的集中趋势、变异状况以及与生长速度有关的参数 ,追踪观察这些儿童自6、7岁至 18岁时共12年的身高变化 ,并做有关参数分析。报告了各年龄组身高生长速度的均值及标准差 ,该组儿童身高生长突增开始年龄 (男10.73±1 .12岁 ,女 9.00± 1.18岁 )及速度 (男4.51± 0.65cm/年 ,女 4.95± 0.79cm/年 ) ;身高生长高峰发生年龄 (男 1 3.0 7±1.08岁 ,女11.32± 1.32岁 )及速度高峰值 (男10 .01± 1.59cm/年 ,女8.13± 1.03cm/年 ) ;以及生长突增结束年龄 (男16.18± 1.02岁 ,女 13.96± 1.09岁 )。分析了最终身高与生长突增有关指标的相关关系。     

Leptin levels in obese children: effects of gender,weight reduction and androgens

Obesity in children is accompanied by increased circulating leptin concentrations. Girls have higher leptin concentrations than boys. The aim of our study was to compare serum leptin levels before and after a five-week weight reduction program and to study the relationship of leptin levels, serum total cholesterol, and androgens (testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate) in 33 obese boys (age: 12.7+/-1.97 years, BMI: 30.46+/-4.54) and 66 obese girls (age: 12.7+/-2.51 years, BMI: 29.31+/-4.62). We found that serum leptin concentrations in obese children were significantly decreased after a weight reduction program (before 20.79+/-9.61 ng/ml, after 13.50+/-8.65 ng/ml in girls; before 12.25+/-10.09 ng/ml and after 5.18+/-3.56 ng/ml in boys, p<0.0001 in both genders). Leptin levels correlated positively with the body mass index before and after weight reduction. There was a positive association in obese boys and a negative one in obese girls between leptin levels and the WHR (waist to hip circumference ratio). Serum leptin also shows a strong relationship to fat distribution (p=0.02 in boys, p<0.0001 in girls). No significant correlation was found between leptin concentrations and total cholesterol or androgens. We confirmed that leptin is a sensitive parameter of body composition and weight reduction in obese children.     

Plasma levels of androgens and 17 alpha-OH-progesterone as an index of the adequacy of treatment in congenital adrenal hyperplasia

Plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA), delta 4-androstenedione (delta 4), testosterone and 17 alpha-OH-progesterone (17-OH-P) were studied in 58 samples collected in 18 patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, during long-term ambulatory treatment with hydrocortisone. At each visit the patients were classified as being either in good control (GC) or in poor control (PC), based on well-defined clinical, auxological and biochemical criteria. The results were analyzed in relation to the degree of control and to chronological age (CA), bone age (BA), body surface (BS) and pubertal development. The most clear distinction between the children with GC and those with PC is found for DHEA-S (p less than 0.001 for BA). The majority of the DHEA-S values in the children with GC are closely grouped and significantly below the normal limits for CA, BA, BS and pubertal stage (p less than 0.001). In contrast, the PC children have wide-spread values, most of them being within or above the normal limits. The difference between GC and PC is also significant for testosterone (p less than 0.01) and delta 4 (p less than 0.05), but not for DHEA. Of the five steroids studied, DHEA-S is the most specific, whereas testosterone is the most sensitive and especially useful in girls and in prepubertal boys. delta 4 and 17-OH-P are almost as sensitive as DHEA-S, but they are less specific. DHEA is the less valid criterium.     

The course of diagnosis in autistic patients: the delay between recognition of the first symptoms by parents and correct diagnosis

The primary aim of the research was to find the delay between the first symptoms of an autistic disorder being recognized by parents and diagnosis in our centre. A secondary objective was to evaluate the number of contacts with professionals (physicians, teachers, and speech therapists) in which parents pointed out special manifestations seen in children and, in spite of that, the children were not referred to a specialist. A retrospective study assessed 204 children (59 girls, 145 boys) in total; 126 children (39 girls, 87 boys) with childhood autism (CHA), 57 (17 girls, 40 boys) with atypical autism (AA), and 21 (3 girls, 18 boys) with Asperger's syndrome (AS). The mean age at appearance of the first signs was 29.7 months (range 0-70, median 30+/-17.0) in N=201, and the average age at diagnosis was 81.5 months (range 13-276, median 69.5+/-45.2) in N=204. The mean delay in making a diagnosis was 51.3 months (range 0-246, median 39+/-40.9) in N=201. The delay in diagnosis is shortest in patients with AA (a mean period of 44.4 months = 3 years and 8 months), longer in CHA patients (49.5 months = 4 years and 2 months), and longest in patients with AS (80.8 months = 6 years and 9 months). A statistically significant difference in the period to diagnosis was found between CHA and AS patients (p=0.023) and between AA and AS patients (p=0.019). The mean number of visits to physicians and other specialists before referring to a specialized centre for diagnosis in N=133 was 2.4 (range 1-5, median 2+/-0.9). The diagnosis of autism is made late and early educational and behavioural interventions cannot be initiated.