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.     

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.     

Precocious or early puberty and growth failure in girls treated for acute lymphoblastic leukaemia

We have studied 41 children with early or precocious puberty who have been treated for acute lymphoblastic leukaemia with prophylactic cranial irradiation (1,800-2,400 cGy) accompanied by intrathecal methotrexate and systemic chemotherapy. Mean age at radiotherapy was 3.9 years (range 1.7-7.7) in the girls and 4.8 years (range 2.6-7.8) in the boys. Mean age at the onset of puberty was 8.6 years (range 6.7-9.7) in the girls and 9.3 years (range 7.8-10.3) in the boys. Of the 41 children with early puberty (greater than 1.4 SD from the mean) 36 were females and 5 were males. 21 of the 36 girls had an absent or inadequate growth acceleration of puberty. 7 of 12 girls who had a pharmacological test of growth hormone (GH) secretion had GH insufficiency (peak level less than 20 mU/l). Early or precocious puberty combined with GH insufficiency may produce severe growth failure and we have used a treatment regimen of a gonadotrophin-releasing hormone analogue, in order to reduce the rate of epiphyseal maturation, combined with biosynthetic GH to increase or sustain growth rate. We have treated 4 girls in this manner. During a mean treatment period of 0.86 years, height SDS for bone age rose from a mean of -1.06 to -0.59. Longer treatment periods will be required to assess the effect on final height.     

Diagnostic utility of a low-dose gonadotropin-releasing hormone test in the context of puberty disorders

OBJECTIVES: The 10-microg gonadotropin-releasing hormone (GnRH) test assesses pituitary gonadotroph responsiveness, whereas the 100-microg dose assesses maximal secretory capacity. Our aims were to establish normative data for the low-dose test in children and to evaluate the test in diagnosing common pubertal disorders. METHODS: We retrospectively classified 107 children who underwent 10-microg GnRH tests into normal prepubertal (20 boys, 10 girls), normal early pubertal (10 boys, 16 girls), constitutional delay of puberty (CDP, 13 prepubertal boys >12 years), hypogonadotropic hypogonadism (HH, 5 prepubertal boys >12 years), central precocious puberty (CPP, 19 girls) or premature thelarche/variant (13 girls). RESULTS: Peak LH response was higher in prepubertal boys >12 years compared with younger boys (p < 0.01) but showed no further change in early puberty. CDP boys had LH responses similar to prepubertal boys >12 years. HH boys showed an absent LH response which diagnosed HH with 100% sensitivity and 96% specificity. Thelarche girls had LH:FSH peak ratios lower than normal prepubertal (p = 0.001), pubertal (p < 0.05) or CPP (p = 0.001) girls. CONCLUSIONS: We have established normative values for the low-dose GnRH test in children. The test successfully differentiated HH from CDP in boys, and contributed to the differential diagnosis of CPP and premature thelarche in girls.     

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.     

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.     

Growth and pubertal development during and after treatment with a slow-release gonadotropin-releasing hormone agonist in central precocious puberty.

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

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)     

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.     

Prediction of advanced puberty by height velocity in children with acute lymphoblastic leukemia.

Pubertal development was retrospectively evaluated in 58 children with cancer, mostly acute lymphoblastic leukemia (ALL), who are in complete remission and off chemotherapy. Six girls [5 patients with ALL, and 1 with malignant lymphoma (NHL)] showed advanced puberty (25.0%, 6 of 24 female patients with ALL and NHL) through the evaluation of their growth velocity. No evidence for advanced puberty was seen in the males. All 6 girls had received cranial irradiation for central nervous system prophylaxis and systemic chemotherapy including glucocorticoid. The mean age at onset of the pubertal growth spurt in these 6 girls was significantly lower than for girls with a solid tumor [6.90 +/- 0.10 and 9.00 +/- 0.77 (mean +/- SD) years, respectively (p < 0.01)]. By simply evaluating the height velocity, we could predict advanced puberty which was ultimately associated with short stature.     

Pubertal growth as a determinant of adult height in boys with constitutional delay of growth and puberty

In boys with constitutional delay of growth and puberty, adult height may be inconsistent with parental (target) height. We aimed at studying which period of growth was important to account for adult height being above or below target height. In this retrospective study, adult height measured after 20 years in 39 patients was compared with target height and height data obtained at about 6 and 12 years of age and at diagnosis of delayed puberty (mean 14.6 years). Twenty-eight patients were untreated while 11 received testosterone enanthate (50 or 100 mg/month for 6 months). The growth data from both groups were pooled since they were not different. On average, the adult height standard deviation score (-0. 6 +/- 0.8, mean +/- SD) was similar to target height (-0.5 +/- 0.6). There were, however, marked individual differences since adult height varied between 1.7 SD (11 cm) below target height and 1.4 SD (9.5 cm) above target height. Multiple regression analysis showed that the most significant determinant of the difference between adult height and target height was height catch up during puberty (p < 0.002). We conclude that the magnitude of height catch up during puberty is a significant determinant of adult height in boys with constitutional delay of growth and puberty. Thus, optimizing pubertal growth may be a relevant therapeutic aim for adult height in boys with short stature and delayed puberty. Copyrightz1999S. KargerAG,Basel     

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)     

Sex hormone-binding globulin and thyroxine-binding globulin levels in premature thelarche

Premature thelarche is defined as the isolated development of breast tissue in girls less than 8 years of age. Although breast development is an estrogen-dependent process, these girls do not have elevated serum estrogen levels, and the hormonal basis for their condition is unclear. We studied the levels of two estrogen-dependent transport proteins, sex hormone-binding globulin (SHBG) and thyroxine-binding globulin (TBG), in order to determine if there was evidence for a more subtle estrogen effect in girls with premature thelarche. SHBG levels in girls with premature thelarche were not significantly different from those of prepubertal girls of the same ages and were significantly lower than those in girls undergoing pubertal development at the appropriate age (P less than 0.05) and in normal women (P less than 0.001). There was no statistically significant difference in TBG levels between the girls with premature thelarche and prepubertal controls. There was also no significant difference in TBG levels between prepubertal girls and girls in early puberty. In contrast, women had TBG levels that were significantly lower than those in all girls studied. We conclude that the estrogen exposure (whether endogenous or exogenous) of girls with premature thelarche is less than that of girls in early true puberty and similar to that of other prepubertal girls. Further, changes in serum TBG are not as sensitive an indicator of estrogen effect as is breast development or changes in SHBG. This study also suggests that large amounts of exogenous estrogens are not an element in the development of premature thelarche.     

Estimating height from arm span measurement in Malawian children

Arm span and standing height were measured in 289 boys and 337 girls aged 6-15 years who were free from physical deformities which can affect stature or arm span. The arm span exceeded height in all age groups of boys and in older girls. At the age of 7, 11 and 12 years girls were significantly taller than the boys and had longer arm span while at the age of 15 years, the trend was opposite. The mean difference between the two anthropometric parameters for boys was 5.45 +/- 4.21 cm (t = 3.556, p < 0.001) and for girls was 4.94 +/- 4.96 cm (t = 3.542, p < 0.001). Correlation coefficient between height and arm span measurements for Malawian boys was 0.983 and for girls was 0.986. Height, arm span and height-arm span difference increased with age of children while height to arm span ratio decreased. The gender difference in height-arm span differences was only significant at the age of 15 years. Multiple regression and cross validation were performed. Height of Malawian children of both sexes can be estimated from equation: Height (cm) = 15.756 + (0.168 x age) + (0.839 x arm span) (SEE = 0.760, R2 = 0.988).     

Experience with growth hormone therapy in Turner syndrome in a single centre: low total height gain, no further gains after puberty onset and unchanged body proportions

The experience gained since 1987, through observation of 85 girls with Turner syndrome under growth hormone (GH) treatment, has enabled the analysis of one of the largest cohorts. Our results show that age, karyotype and height reflect the heterogeneity of the patients examined at our growth centre. In 47 girls, followed over 4 years on GH (median dose 0.72 IU/kg/week), the median age was 9.4 years and mean height SDS was -3.55 (Prader) and -0.14 (Turner-specific), while height and other anthropometrical parameters [weight, body mass index, sitting height (SH), leg length (LL) SH/LL, head circumference, arm span] were documented and compared to normative data as well as to Turner-specific references established on the basis of a larger (n = 165) untreated cohort from Tübingen. The latter data are also documented in this article. Although there was a trend towards normalization of these parameters during the observation period, no inherent alterations in the Turner-specific anthropometric pattern occurred. In 42 girls who started GH treatment at a median age of 11.8 years, final height (bone age >15 years) was achieved at 16.7 years. The overall gain in height SDS (Turner) from start to end of GH therapy was 0.7 (+/- 0.8) SD, but 0.9 (+/- 0.6) SD from GH start to onset of puberty (spontaneous 12.2 years, induced 13.9 years) and -0.2 (+/- 0.8) from onset of puberty to end of growth. Height gain did not occur in 12 patients (29%) and a gain of > 5 cm was only observed in 16 patients (38%). Height gain correlated positively with age at puberty onset, duration, and dose of GH, and negatively with height and bone age at the time GH treatment started. Final height correlated positively with height SDS at GH start and negatively with the ratio of SH/LL (SDS). We conclude that, in the future, GH should be given at higher doses, but oestrogen substitution should be done cautiously, owing to its potentially harmful effect on growth. LL appears to determine height variation in Turner syndrome and the potential to treat short stature successfully with GH.     

Adult height in congenital hypothyroidism: prognostic factors and the importance of compliance with treatment

OBJECTIVE: To study the growth, puberty and compliance of 66 hypothyroid children and to determine prognostic factors for adult height. PATIENTS: 66 children were included (12 boys, 54 girls). Aetiologies were 43 ectopic glands, 14 thyroid agenesis, 9 dyshormonogenesis. RESULTS: In girls the mean adult height was 164.7 +/- 6.5 cm for a target height (TH) of 162.8 +/- 5.4 cm. In boys the mean adult height was 178.2 +/- 6.4 cm for a TH of 175.7 +/- 4.7 cm. Puberty development was normal. Children who exceeded their TH had an earlier start of treatment versus children who failed to reach their TH: 24.8 +/- 13.5 vs. 42.0 +/- 47.3 days, p = 0.004. Delayed normalisation of TSH is a risk factor for bad compliance. Adequate correlations between treatment variables appeared only in children who exceeded their TH. CONCLUSIONS: TH, day of start of treatment and compliance with treatment are the main prognostic factors for adult height. Early detection of bad compliance is possible.     

Prepubertal growth in children with long-term parenteral nutrition

In children who depend on long-term parenteral nutrition (PN), a major goal is to obtain optimal growth. The aim of this retrospective study was to analyze growth in children on long-term cyclic nocturnal home PN, over at least 8 years before puberty. Nine boys and 7 girls were studied. Their mean age at the time of study was 11 years with a mean PN duration of 10.5 (8.6-16.4) years. Diseases were short bowel syndrome (5), intractable diarrhea (4), chronic intestinal pseudo-obstruction (4) and long segment Hirschsprung's disease (3). In each child, periods of at least 2 years were analyzed: either periods of regular growth (R: height gain >50th percentile), or slow growth (S: height gain < or =25th percentile). Results were expressed as mean +/- SD. Comparisons were performed using either Student's test for unpaired data or Wilcoxon's test for paired data. PN provided a mean of 224 +/- 80 mg nitrogen/kg/day and 43 +/- 14 kcal/kg/day equivalent to 50% of recommended supplies. At the time of study, the population presented with weight (W) = -0.7 +/- 0.8 SD and height (H) = -1.5 +/- 1.3 SD. The difference between W and expected W for H (W/H) was significant (p < 0.002). W/H ratio was 105 +/- 11%. For the total PN duration, weight gain was +0.2 +/- 1.5 SD and height loss was -0.75 +/- 1.4 SD. An excess weight gain occurred in parallel with the deflection of height gain. Of the 16 children, regular prepubertal growth was achieved in 4 only. The other 12 showed alternate periods of R and S. In 8 of them, 26.5 years of R and 33.5 years of S were compared, each child being his own control. PN nitrogen and energy supplies were significantly higher during R periods than during S periods. In the absence of any disease or treatment explaining the failure to thrive, inadequate PN supplies, especially in terms of nitrogen supply, are thought to be responsible for a negative nitrogen balance and slowed growth. In case of any deflection away from the individual growth curve, it is recommended to adjust the PN supply early, especially nitrogen supply.     

Growth analysis up to final height and psychosocial adjustment of treated and untreated patients with precocious puberty

Thirty-four patients (27 girls and 7 boys) with precocious puberty who had reached final height were examined in order to analyze their growth. Thirty patients were diagnosed as having idiopathic precocious puberty, while 4 patients had cerebral organic disorders. Twenty-two patients were treated with cyproterone acetate, 3 with medroxyprogesterone acetate, and 9 patients remained untreated. Growth data of these three groups showed no differences, and final height was not affected by treatment. In patients with precocious puberty, adult height was significantly more often in the lower percentiles (less than or equal to P25, corresponding to an SDS of -0.67) than expected. In both treated and untreated patients, any negative influence of the early onset of puberty on well-being in later life could not be established.     

Adrenal steroidogenic defects in children with precocious pubarche.

The occurrence of nonclassical congenital adrenal hyperplasia among children with precocious pubarche is still a matter of debate. We studied the adrenal steroid response to ACTH stimulus (Synacthen, 0.25 mg i.v. bolus) in 26 Italian children (5 boys, 21 girls) who had presented pubic hair, without other signs of virilization, at ages ranging between 0.45 and 8.8 years. The control groups comprised 8 prepubertal children (5 boys, 3 girls) and 12 children at Tanner stage 2 for pubic hair development (1 boy, 11 girls). Two patients were diagnosed as having nonclassical congenital adrenal hyperplasia: 1 due to 21-hydroxylase deficiency, the other due to 3 beta-hydroxysteroid-dehydrogenase deficiency. The remainder, classified as having idiopathic precocious pubarche (PP), had adrenal androgens higher than normal prepubertal children and similar levels to those observed in early pubertal controls. In contrast to a recent report, we confirmed that mild adrenal enzymatic defects can occur in PP, and, consequently, the use of ACTH testing in children with PP seems to be recommended.