Height Velocity SDS Research Articles

Body mass index and segmental proportion in children with different subtypes of psychosocial short stature.

We describe change in height, segmental proportion and weight in 46 children (19 girls, 27 boys, all but four prepubertal) diagnosed by a multidisciplinary team as having psychosocial short stature (PSS) who had a change in their environment (31 were separated from their family). The classification of PSS has recently been modified to include appetite disturbance at presentation: hyperphagic (IIA), non-hyperphagic (IIB) and anorexic type (III). The 46 patients were subdivided into these three classifications and analysed separately concerning their auxology and change in body mass index before and after intervention. Although in all groups a significant improvement in height velocity SDS was seen after intervention, subtle differences in body proportions could be demonstrated. Proportional short stature was seen in both non-anorexic types of PSS (type IIA and type IIB) and did not change with intervention, whereas a significant change in body proportion was found in the anorexic type (type III). Body mass index at presentation was within normal limits and did not increase significantly in any of the three subgroups after intervention. the main diagnostic feature of psychosocial short stature is catch-up growth after change of environment which occurs in almost all patients. The classification on the basis of appetite disturbance was supported by our auxological data with specific differences in body proportions.

Effect of treatment on growth in congenital adrenal hyperplasia.

In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect.

Influence of growth hormone on a new marker of cartilage metabolism (chondrex).

The aim of this study was to evaluate the usefulness of a major secretory protein of human chondrocytes (chondrex) as a potential serum marker of bone responsiveness to growth hormone (GH). The study included 18 children (10 F, 8 M), aged 10.9 +/- 2.3 years, bone age 8.8 +/- 2.7 years, height -2.3 +/- 0.22 SDS, affected by isolated idiopathic GH deficiency (GHD). Serum samples for evaluation of chondrex, total, and bone alkaline phosphatase were taken before and 3 and 6 months following treatment with rhGH. The basal serum level of chondrex did not differ between patients (37 +/- 22 ng/ml) and controls (33 +/- 9.8 ng/ml). Following 6 months of treatment with rhGH, a significant increase of height velocity SDS (from -2.8 +/- 0.5 to 1.3 +/- 0.7), total (from 195 +/- 47 to 264 +/- 79 U/liter) and bone alkaline phosphatase (from 81 +/- 21 to 108 +/- 30 U/liter) was observed, while chondrex serum level remained unchanged (from 37 +/- 22 to 36 +/- 29 ng/ml). It was concluded that chondrex cannot be considered a reliable marker of bone responsiveness to GH in the growing child.

Reduced spontaneous growth hormone secretion in patients with Turner's syndrome

Pirazzoli P, Mazzanti L, Bergamaschi R, Perri A, Scarano E, Nanni S, Zucchini S, Gualandi S, Cicognani A, Cacciari E. Reduced spontaneous growth hormone secretion in patients with Turner's syndrome. Acta Pædiatr 1999; 88: 610‐3. Stockholm. ISSN 0803‐5253We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7 ± 3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty‐nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH‐deficient girls (GH peaks < 8 μg/l after pharmacological tests) and both groups were lower (p < 0.0001 and p < 0.0005, respectively) than MGHCs of 27 short normal girls (GH peak > 8 μg/l). MGHC of the patients with TS was negatively correlated (p < 0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE < 20% was significantly higher (p < 0.02) than that of the TS patients with BWE > 20%, but again did not differ from that of the GH‐deficient patients and was lower (p < 0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty‐four percent of the TS patients showed GH responses to pharmacological tests < 8 μg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH‐deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment. □Bodyweight excess, growth hormone secretion, growth hormone therapy, Turner's syndrome

Reduced spontaneous growth hormone secretion in patients with Turner's syndrome.

We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7+/-3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty-nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH-deficient girls (GH peaks < 8 microg/l after pharmacological tests) and both groups were lower (p < 0.0001 and p < 0.0005, respectively) than MGHCs of 27 short normal girls (GH peak > 8 microg/l). MGHC of the patients with TS was negatively correlated (p < 0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE < 20% was significantly higher (p < 0.02) than that of the TS patients with BWE > 20%, but again did not differ from that of the GH-deficient patients and was lower (p < 0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty-four percent of the TS patients showed GH responses to pharmacological tests < 8 microg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH-deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment.

Growth in children with craniopharyngioma following surgery.

Hypopituitarism, including severe GH deficiency, is an almost inevitable outcome of craniopharyngioma. However, some GH deficient children with this tumour may grow normally or even have accelerated growth postoperatively. To study this phenomenon we have investigated the endocrine status, including IGF-1 and its binding proteins IGFBP-1 and IGFBP3, in children referred for follow-up at various time intervals after surgery. Twenty-five patients (14 boys and 11 girls, aged 3.8-18.9 years), were studied on 34 occasions between 0.5 to 10.8 years after surgery. The tumour was intrasellar in 11 cases and suprasellar in 14. Height and height velocity were recorded as SDS values. Body mass index (BMI) was calculated as weight/height2. GH secretory status was evaluated by stimulation both with oral clonidine and with GH releasing hormone. Serum insulin (INS) levels were studied following an oral glucose load. IGF-1, IGFBP-3, IGFBP-1 and prolactin serum concentrations were evaluated in fasting samples. All hormones were measured by radioimmunoassay. All patients had growth hormone (GH) deficiency. Height (HtSDSCA) and height velocity SDS for chronological age (HVSDSCA) decreased progressively after surgery (r = -0.47, P = 0.005, and r = -0.4, P = 0.032, respectively) but four patients had normal HtSDSCA 6.1 to 10.8 years following their first surgery. There was a significant correlation between BMI and HtSDSCA (r = 0.37, P = 0.03). BMI in children with suprasellar craniopharyngioma was significantly greater than that in patients with intrasellar tumour (23.3 +/- 7.0 vs. 17.3 +/- 1.4 kg/m2; P = 0.001). In 13 of 33 cases oral glucose load was accompanied by hyperinsulinaemia with serum INS levels greater than 50 mU/l. The mean area under the curve (AUC) of INS after glucose load (INSAUC) in the suprasellar group was greater than in the patients with intrasellar lesion (6945.5 +/- 4411.8 vs. 2495.5 +/- 1768.8 mU/l. min P = 0-001). The log INSAUC correlated significantly with HtSDSCA (0.37, P = 0.03). Fasting serum IGF-1 and IGFBP3 levels were normal in 8 and 12 of the 31 measurements, respectively. Both IGF-1SDS and IGFBP-3SDS correlated significantly with HtSDSCA (r = 0.77, P = 0.0002 and r = 0.65, P = 0.0001, respectively) and the log INSAUC (r = 0.39, P = 0.035, r = 0.56, P = 0.002, respectively). As determined by forward stepwise regression analysis, IGF-1SDS was the single most important predictor of HtSDSCA (R2 = 0.33, P = 0.001) in the subset mode. A few children with craniopharyngioma grew normally after surgery, in spite of being GH-deficient. This growth phenomenon, which is usually accompanied by obesity, was more common in patients with suprasellar tumour and is likely to be associated with the effect of IGF-1 bioavailability, which, in turn, may be modulated largely by insulin.

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome.

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 pre-pubertal children with Noonan syndrome, aged between 5.4 and 14.3 y, and all with a height < 1.4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0.15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean +/- SD height velocity increased by 4.0 +/- 1.6 cm/y in the Noonan syndrome group and by 3.6 +/- 1.3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0.53 +/- 0.46 (p < 0.001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight (r = 0.48, p < 0.05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.

Treatment and disease effects on short-term growth and adult height in children and adolescents with 21-hydroxylase deficiency.

In clinical practice, height velocity and rate of bone maturation during each follow-up interval are among the parameters used to modify glucocorticoid treatment in children with 21-hydroxylase deficiency. There is controversy on the relative importance of treatment and disease variables for short-term growth and final height. Short- and long-term growth data of 87 patients (n = 35 salt-wasting form; n = 52 simple virilizing form) were analysed retrospectively by stepwise multiple regression. Height SDS for chronological age (HtSDSCA) was elevated prior to treatment in boys (m = 3.22, p < 0.0001) and decreased when compared to HtSDSCA > or = 4 years after the start of treatment in both boys (m = -0.64, p < 0.0001) and girls (m = -1.24, p < 0.0023). When the simultaneous effects of hydrocortisone dose, salt-wasting status, degree of hormonal control, and patient sex on short-term growth between follow-up visits were analysed, only a minor effect of hydrocortisone dose (partial coefficient of determination [Pr2] = 0.04, p < 0.011) and salt-wasting status (Pr2 = 0.03, p < 0.024) in the prepubertal group, and a small effect of the treatment quality rating in the pubertal group (Pr2 = 0.07, p < 0.0042) on height velocity SDS for chronological age (HVSDSCA) were noted. Height velocity SDS for bone age (HVSDSBA) was influenced to a similar degree by treatment quality (Pr2 = 0.098, p < 0.0017) in the prepubertal, and by hydrocortisone dose (Pr2 = 0.063, p < 0.021) in the pubertal group. Mean daily hydrocortisone doses used in normally growing patients ranged between 17.9 and 21.8 mg/m2/d if analysed separately for sex and salt-wasting status. 34 patients had reached final height which with the exception of one boy was below the population mean and ranged from 82.3% to 100.1% of target height in the total group. 41.2% of the patients had adult short stature (HtSDS < -2). Treatment with synthetic glucocorticoids for more than 1 year started before the age of 1.5 years was associated with the most severely compromised final height SDS (m = -3.73, p < 0.029). The proportion of the short-term height velocity SDS that can be explained by the tested treatment and disease variables is low (< or = 9.8%). Conclusions drawn from observed changes in height velocity during single short follow-up intervals on treatment modalities must therefore be viewed with caution. In the long run, however, use of daily hydrocortisone doses > 25 mg/m2/day and of synthetic glucocorticoids started early in the course of the disease does not only lead to a transient deceleration of height velocity in growing children with 21-hydroxylase deficiency, but carries a definite risk for decreased final height.

Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth.

The recognition of the syndrome of adult GH deficiency suggests that young GH deficient adults, deprived of GH replacement at completion of linear growth, may suffer effects of GH deficiency. We assessed GH reserve in young adults previously diagnosed as having idiopathic GH insufficiency, who were treated with hGH replacement (14 IU/m2/week) in childhood. Eight patients (7 males, 1 female) diagnosed as having GH insufficiency by insulin tolerance test (ITT) in childhood (ages 8.5-15.6 years) were retested by ITT at completion of linear growth (ages 15.1-19.6 years), 3 months after discontinuation of hGH therapy. GH reserve was measured during ITT at diagnosis and at retesting. Height velocity (HV) and HV SDS were calculated before and during GH therapy. At diagnosis, the mean peak GH response to ITT was 10.5 +/- 2.0 mU/l (range 7.7-13.6). At retesting, mean GH was 52.4 +/- 33.2 mU/l (range 10.4-100), 7/8 subjects having peak GH levels greater than 15 mU/l. During hGH therapy mean HV increased from 4.0 +/- 1.5 cm/year at diagnosis to 7.3 +/- 1.9 cm/year during the 1st year (P = 0.004) and 6.9 +/- 2.3 cm/year during the 2nd year (P = 0.02). Mean HVSDS increased from -1.6 +/- 2.1 at diagnosis to 3.1 +/- 2.9 during the 1st year (P = 0.004) and 2.2 +/- 4.2 during the 2nd year (P = 0.05, NS) of treatment. Seven out of 8 children diagnosed as having idiopathic GH insufficiency had normal GH secretion at completion of linear growth. Children with GH insufficiency cannot be assumed to become GH deficient adults and should not continue on GH therapy into adult life without reinvestigation. All who were GH insufficient children should be retested at completion of linear growth to identify those who are truly GH insufficient adults and may benefit from replacement therapy.

Final height of short normal children treated with growth hormone

Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone (r-hGH) to short normal children. We describe the effect of such treatment on final height. This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children (height standard deviation score [SDS] -2.17 [range -1.8 to -3.3]; height velocity SDS -0.44 [0.33]; peak serum GH response to stimulation 27.9 mU/L [9.2] were treated with r-hGH, and 7 short children who declined treatment (height SDS -2.34 [0.61]; height velocity SDS -0.36 [0.28]; peak serum GH response 28.2 mU/L [6.8]) acted as an observation group. Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week (0.02-0.04 mg/kg per day) for the first 2 years of treatment and 20 U/m2 per week thereafter, 3 untreated children were lost to long-term follow-up. r-hGH significantly increased the difference in final height compared with pretreatment predicted height (+0.42 SDS [0.79], p = 0.03) but this change was not significantly greater than that of the observation group (+0.16 SDS [0.20]). Treatment had no effect on the timing of puberty. Boys progressed slightly faster through puberty, associated with an acceleration in bone-age maturation. No untoward effects on glucose metabolism were observed. Long-term therapy did not alter body-fat distribution or blood pressure. Long-term therapy in this group of children appears safe but the small increment in final height, approximately 2.8 cm in boys and 2.5 cm in girls, does not justify the widespread use of r-hGH for short normal children.

Growth response to growth hormone therapy in patients with different degrees of growth hormone deficiency.

Growth response to GH therapy in prepubertal patients with idiopathic GH deficiency (GHD) was analyzed in terms of the chronological age at the start of GH treatment and the GH secretory capacity, by using the large database provided by the International Cooperative Growth Study (ICGS) Japan. 1192 patients, aged from 3 to 10 years were divided into three groups with the following maximum GH values in GH stimulation tests: Group A: both < or = 5 ng/ml, group B: both 5-10 ng/ml, group C: one > 10 ng/ml. Analysis of age-related growth response using with delta height SDS (delta height SDS) as a response variable revealed that the group A patients responded better to GH, while there was no differences between the other groups. Simple and multiple regression analysis showed that IGF-I and chronological age (CA) negatively correlated with growth response, and target height SDS-height SDS positively correlated. These three most important predictors accounted for 49% of the variation in the growth response in group A, whereas six variables such as CA, frequency of GH injection, % overweight, GH dose, target height-height SDS, and pretreatment height velocity SDS accounted for only 28% of those in groups of B and C. These results lead us to conclude that growth response to GH is related to the degree of GH impairment with its cut-off level of 5 ng/ml. From these findings it might be suggested that treatment regimen should be tailored to individual requirements according to the degree of GHD.

Experience in Growth Hormone Therapy in Noonan Syndrome in Japan

Thirty-nine children with Noonan syndrome were treated with growth hormone (GH). Prepubertal height velocity was 4.25 ± 1.31 cm/year (M ± SD) (n=38) before GH therapy, which was increased to 6.23 ± 0.87 cm/year (n=33) in the first year, to 4.92 ± 1.15 cm/year (n=22) in the second year and 4.76 ± 1.25 cm/year (n=13) in the third year. Height velocity SDS for chronological age and height velocity (SDS) for bone age were also improved in the 1st year, but declined progressively during the subsequent years. No adverse effects were observed during GH treatment.These data indicate that GH may be effective in Noonan syndrome, but further studies are required to evaluate the efficacy of long-term GH therapy on adult height and body proportions.

Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids.

We describe 6 (4F, 2M) prepubertal children with moderate asthma diagnosed at a mean age of 2.8 years. All patients were treated with inhaled corticosteroids in a dose of between 300 and 800 mcg of beclomethasone dipropionate (becotide) daily, given either as an aerosol or rotahaler. Mean height velocity SDS decreased from -0.8 (range +0.5 to -2.0) to -3.2 (range -1.3 to -4.8) when the dose was increased. Alternatively, when the dose was reduced or stopped, mean height velocity SDS increased from -3.2 (range -2.0 to -4.8) to +0.8 (range -1.2 to +2.7). Careful assessment of height velocity is indicated in all children receiving treatment with inhaled corticosteroids.

The use of recombinant human growth hormone in short children with chronic renal failure.

Regulation of the somatotropic axis is altered in chronic renal failure (CRF) resulting in a secondary syndrome of growth hormone (GH) insensitivity. Secretion of growth hormone estimated by deconvolution analysis is low normal in prepubertal patients and reduced in late pubertal children with CRF. Basal and integrated GH serum concentration measured by RIA is increased due to reduced renal metabolic clearance, whereas the fractional urinary excretion is increased due to damage of renal tubular cells. GH receptor mRNA is decreased (rat) and the serum concentration of GH binding protein (BP) activity is low (man). Insulin-like growth factor (IGF)-1 production rate is reduced, whereas serum concentrations of IGFBPs are increased secondary to reduced renal metabolic clearance. This results in a reduction of free, active IGF-1. Treatment with GH induces a rise in serum IGF-1 concentration and normalizes IGF bioactivity. Clinical studies in prepubertal children demonstrated a dramatic rise in height velocity during the first treatment year and to a lesser extent during the following years. In children on conservative treatment prior to dialysis, mean height SDS improved by 1.5 within two years and by 2.0 within four years. Patients with renal allografts responded in a similar way. Age and pretreatment height velocity SDS are confounding variables for the response to GH. Renal function seems not be altered by recombinant human (rh) GH in patients with CRF, and the number of renal allograft rejection crises seems not to be substantially increased under rhGH treatment in allograft recipients.

Long‐term treatment with growth hormone in Noonan's syndrome

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of ‐2.1 (range ‐4.1 to ‐ 0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from ‐3.3(range ‐4.2 to ‐2.2)to ‐2.4(range ‐3.3 to ‐ 1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was ‐2.1) (range ‐3.1 to ‐ 1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from ‐1.8 (range ‐ 2.8 to ‐ 09) to ‐1.2 (range ‐ 1.6 to ‐0.6).

Long-term treatment with growth hormone in Noonan's syndrome.

Five children (four boys, one girl) with Noonan's syndrome were treated with growth hormone for a mean of 2.9 (range 1.8 to 4.6) years. Treatment was commenced at a mean age of 3.9 (range 2.5 to 6.0) years. After one year of treatment, height velocity SDS increased from a mean of -2.1 (range -4.1 to -0.3) to a mean of +3.1 (range +2.0 to +3.5). Subsequently, height SDS increased significantly from -3.3 (range -4.2 to -2.2) to -2.4 (range -3.3 to -1.6). Although in all patients a marked decrease in height velocity was observed in the following years of treatment, compared to the first year, height SDS continued to improve in comparison to pretreatment (mean height SDS in the third year for four patients was -2.1) (range -3.1 to -1.4). In the four patients who had completed their second year of treatment, height SDS for bone age had increased from -1.8 (range -2.8 to -0.9) to -1.2 (range -1.6 to -0.6).

LONG-TERM GROWTH DATA AND GROWTH HORMONE SECRETION IN 65 PATIENTS WITH PSYCHO-SOCIAL DWARFISM

We describe the growth of 65 children (32 girls, 33 boys) from 51 families with an average age of 6.6 years (range, 0.9 to 16.5 years, all but 5 prepubertal) diagnosed by a multidisciplinary team as having environmental growth failure. 27 of our patients had occult sexual or physical abuse (group A), in 15 such abuse was highly suspected (group B), but in 23 only emotional deprivation could be related to growth failure (group C). 51 (78%) patients had an endocrine assessment, of whom 34 (67%) had repeated testing (25 (49%) during one uninterrupted hospital admission). 14 (41%) showed reversible growth hormone deficiency, 9 (26%) increased their growth hormone peak level during one admission, 6 (18%) had growth hormone deficiency in repeated testing. In all patients from group A and B the repeated testing demonstrated a noticeable result. Following an insulin stimulation test, only 4 patients demonstrated a cortisol peak concentration of less than 450 nmol/l. The average weight gain during hospital admission was 274 g/week. 27 patients had a change in their environment (10 were separated from their family), all had an increase In their height velocity SDS (from −0.76 (SD 1.6) to +2.39 (SD 2.5)), and 19 (70%) showed catchup growth (change in height velocity >2). 15 patients were treated with growth hormone before the diagnosis of psycho-social dwarfism was appreciated, and 4 (26%) achieved catch-up growth. All 7 patients who had growth hormone treatment coincident with environmental change achieved catch-up growth.

THE IMPACT OF DOSAGE ON THE EFFECT OF GROWTH HORMONE THERAPY IN CHILDREN WITH IDIOPATHIC SHORT STATURE

The growth response to growth hormone (GH) therapy in children with idiopathic short stature (ISS) is generally characterized by a rapid height velocity (HV) increment followed by a progressive decline. There are no data about the dose-response relationship in such children. We studied 24 children (19 M, 5 F) with ISS and a HV < P25, who, after two years of observation, underwent GH therapy over 3 years in three regimens: gr 1 and 2 received 3 and 4.5 IU/m2 b.s. 6 times per week, and gr 3 received 3 IU/m2 in the 1st year and 4.5 IU thereafter. The median HV SDS was -1.8 in the preinclusion year, and 0.3 in the pretreatment year (p<0.05). In the 1st year on GH the mean (SD) HV SDS rose from 0.4 (1.5) to 5.7 (2.4) on 3 IU/m2 (gr 1+3) and from 0.1 (0.7) to 7.1 (2.1) on 4.5 IU/m2. There was no statistical difference between the groups. In the 2nd and 3rd year the prepubertal children from all groups showed a similar decrease. Mean height SDS increased by 1.2 in all groups, compared to 0.3 in an untreated control group (n=40). Mean bone age (BA) in gr 1,2 and 3 increased by 3.4, 3.0 and 3.9 years (NS between groups). Predicted adult height SDS (Bayley Pinneau) increased by 1.6 (0.8) in group 2 (p=0.01), but not in groups 1 and 3 (p=0,31 and p=0.13). In conclusion: 1) short children selected on the basis of a low HV show a normal mean velocity in the next year; 2) the three dosage regimens lead to a similar initial growth acceleration followed by a similar decrease; 3) the higher dosage appears more effective in terms of predicted adult height, although attained final heights have to be awaited for definitive conclusions.

GROWTH OF CHILDREN AFTER LIVER TRANSPLANTATION (LT): LONGITUDINAL AND CROSS-SECTIONAL STUDY

Aims: to study the growth of children with liver disease before and after LT.Methods: longitudinal study (LS): 16 infants (9 M. 7 F); age 0.73 to 2.38 years (X 1.39) at LT; mean height (Ht) SDS at LT: −2.02 (SD 1.25). Post-LT medication: cyclosporine in tapering doses; prednisone, by daily regimen (DP) for the first 6-12 months, with tapering doses depending on clinical course, then on alternate day regimen (ADP). Cross-sectional study (CSS): 95 children (55 M. 40 F) aged 0.17 to 14.88 (X 3.83), observed before LT, after LT on DP, and on ADP (same medication).Results: LS: pre-LT height velocity (HV) SDS (x±SD −0.60±1.31) significantly lower (p<0.01) than ADP-HVSDS (2.84±1.59) but not significantly different from DP-HVSDS (−1.37±1.66). CSS: DP-HtSDS (X±SD −1.9±1.32) significantly lower (p<0.01) than pre-LT-HtSDS (−1.07±1.06) and ADP-HtSDS (−0.98±1.23). Similar results for sitting height (SH) SDS and subischial leg length (SLL) SDS: pre-LT and ADP-SLLSDS significantly greater than pre-LT and ADP-SHSDS (p=0.01); DP-SLLSDS not significantly different from DP-SHSDS. Significant improvement of head circumpherencc SDS and skinfold SDS on ADP.Conclusions: growth in children with liver disease does not improve after LT on DP while shows catch-up growth on ADP; therefore, it mainly depends on clinical course and cortieosteroid regimen.

Growth and pubertal development in nephropathic cystinosis.

In a retrospective investigation growth and pubertal development were evaluated in 30 patients with nephropathic cystinosis. Growth was investigated during the stage of chronic renal insufficiency as well as after successful kidney transplantation and growth rates were related to kidney function. Pubertal development was evaluated in 17 patients between 12 and 25 years of age. Prepubertal growth rates were stable in a range between -2 and -3 height velocity SDS as long as glomerular filtration rate was above 20ml/min per 1.73m2. A decrease in glomerular filtration rate below this threshold was followed by further decrease in height velocity. After kidney transplantation a significant catch-up growth was seen if immunosuppression was performed with cyclosporine A and low dose prednisolone. This did not occur if conventional therapy with azathioprine and high-dose prednisolone was used. Onset of puberty was delayed in all patients. Gonadotropin and oestradiol levels in female patients showed normal fluctuations according to ovulatory cycles. In male patients after puberty there was an increase in gonadotropin levels above the normal range for adult men while testosterone levels remained in the low normal range. These results indicate that adult men with nephropathic cystinosis may develop hypergonadotropic hypogonadism.