Luteinizing hormone (LH) and estradiol suppression and growth in girls with central precocious puberty: is more suppression better? Are pre-injection LH levels useful in monitoring treatment?

CONTEXT: Girls with central precocious puberty (CPP) are treated with gonadotropin releasing hormone (GnRH) analogues to suppress puberty. Gonadotropin levels are used to monitor treatment, since estradiol is difficult to measure at low levels. The optimal degree of hormonal suppression is still unknown. OBJECTIVE: We hypothesized that in girls treated for CPP, estradiol levels (by ultrasensitive bioassay) would correlate with the rate of skeletal maturation and linear growth velocity. We asked whether predicted height would improve with greater luteinizing hormone (LH) and estradiol suppression. We also compared pre- and post-injection LH levels for monitoring treatment. DESIGN: Thirty girls with CPP were followed for up to 2 years during treatment with leuprolide acetate depot at a dose of 0.3 mg/kg/28 days. We measured LH and estradiol levels, bone age, and growth velocity every 6 months. RESULTS: Estradiol levels were suppressed to below the detection limit in three-quarters of the girls and did not correlate with the rate of skeletal maturation or linear growth. Improvement in predicted height correlated significantly with lower pre-injection LH levels. These girls have some of the lowest estradiol and LH levels, best improvement in predicted height, and least amount of bone age advancement published to date. Pre- and post-leuprolide injection LH levels were positively correlated. CONCLUSIONS: Greater LH suppression may improve height outcome in girls treated for CPP with GnRH analogues. The degree of LH suppression achieved is individualized and not necessarily related to absolute dose. Pre-injection LH levels may be useful for monitoring treatment. Ultrasensitive estradiol levels were very low and usually unmeasurable, affirming the increased suppression at the higher doses of GnRH analogue used in these girls. Further investigation is needed, with longer treatment duration, a range of doses, and ultimately final height. Until such studies are completed, clinicians should be cautious when interpreting pubertal suppression.     

Serum leptin levels during childhood and adolescence: relationship with age, sex, adiposity and puberty

We studied serum leptin levels in 189 healthy children to evaluate related factors during childhood and adolescence. Leptin correlated with body mass index (BMI), triceps skinfold thickness (p<0.001) and body weight (p<0.01). Obese children and girls had higher leptin levels than non-obese children and boys, respectively (p<0.001). In girls, leptin correlated positively with age, skinfold thickness and BMI (p<0.001). In boys, leptin correlated negatively with age (p<0.001) and positively with skinfold thickness (p<0.05). Prepubertal boys had higher leptin levels than prepubertal girls and pubertal boys (p<0.05). Pubertal girls had higher leptin levels than prepubertal girls and pubertal boys (p<0.001). Leptin levels in girls were higher at Tanner stages 4 and 5 than at stage 1 (p<0.001). In conclusion, serum leptin levels are related with adiposity, have obviously age-related gender differences during childhood and adolescence, and may be involved in the maturation of reproductive capacity.     

Estradiol levels in girls with Turner's syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay

Based on growing evidence that estradiol is produced in small amounts even in the prepubertal ovary, we hypothesized that estradiol levels in girls with Turner's syndrome (TS) are lower than in normal prepubertal girls secondary to the lack of normally functioning ovaries. Estradiol levels in untreated girls with TS have not been previously well defined because of the lack of adequate sensitivity of previously available estradiol assays. We utilized an ultrasensitive assay to study estradiol levels in 34 girls with TS and 34 normal age-matched prepubertal girls between the ages of 5 and 12 years. The average estradiol level in the girls with TS (6.4 +/- 4.9 pmol/l estradiol equivalents) was significantly lower than in the normal prepubertal girls (12.7 +/- 10.8 pmol/l estradiol equivalents; p < 0.01). Girls with TS were significantly shorter, and weighed less than the normal prepubertal girls, as expected. The estradiol level was not significantly correlated with height, bone age, or degree of bone age delay. In conclusion, girls with TS have significantly lower estradiol levels than normal age-matched prepubertal girls. This report is consistent with the hypothesis that the lack of normal ovarian function in girls with TS is evident even before puberty.     

Reference values for morning salivary cortisol concentrations in healthy school-aged children

INTRODUCTION: In children, sensitive, specific, pain-free sampling methods are important. An alternative is salivary sampling. Our knowledge about steroid levels in saliva and plasma in school-aged children and during puberty is sparse and contradictory. AIM OF THE STUDY: To estimate salivary cortisol concentrations in healthy school-aged children and relate the concentrations to age, sex, stage of puberty and adult values. PATIENTS AND METHOD: Saliva was collected in Salivette tubes from 210 boys and 176 girls aged 7-15 years, and from four adults, between 08.00 and 09.00 h. The tubes were centrifuged and then frozen at -20 degrees C until analysed by a commercial RIA-cortisol kit. RESULTS: Salivary cortisol was measurable in all infants. Boys and girls had nearly the same median concentrations, 8.8 versus 8.6 nmol/l, but girls had a higher maximal level, 53.9 compared to 33.2 nmol/l in boys. The median concentration was lower in 7-9 year-old children, 7.2 in boys and 5.7 nmol/l in girls, compared to 10-12 year-old children, 11.5 in boys and 10.9 nmol/l in girls (p <0.001). The median concentrations in most age groups were lower than in adults. Salivary cortisol concentration was dependent on stage of puberty. CONCLUSION: Salivary cortisol was measurable in the morning in school-aged children and the median concentration was dependent on age, stage of puberty, but not on sex.     

Diurnal salivary cortisol concentration in school-aged children: increased morning cortisol concentration and total cortisol concentration negatively correlated to body mass index in children with recurrent abdominal pain of psychosomatic origin

INTRODUCTION: The sampling method for salivary cortisol is sensitive, specific and pain-free. Our knowledge about cortisol concentration in saliva and plasma in school-aged children is sparse and contradictory. AIM: To estimate diurnal variation in salivary cortisol concentration in children with and without psychosomatic recurrent abdominal pain (RAP), and to compare groups and relate the concentrations to age, sex, puberty, body mass index (BMI), allergy, headache and ethnicity. CHILDREN AND METHOD: Saliva was collected in 'Salivette' tubes from 159 healthy girls and 147 healthy boys, aged 5-15 years, and from 25 girls and 6 boys, aged 6-18 years, with RAP of psychosomatic origin, at 08.00 h, 13.00 h and 20.00 h. Saliva was analysed using a commercial RIA-cortisol kit. RESULTS: The median concentrations in healthy girls and boys were 8.8/8.3 nmol/l at 08.00 h, 5.5/5.3 nmol/l at 13.00 h, and 2.1/2.3 nmol/l at 20.00 h, respectively. Cortisol concentrations differed between 6-7 year-old and 9 year-old children (higher in the former). Age-matched post-menarcheal girls had higher cortisol concentrations in the evening, 2.2 vs 1.7 nmol/l (p = 0.03). The results were independent of BMI, headache and allergy. In the RAP group, diurnal cortisol concentrations in girls/boys at the different time-points were 14.8/12.9, 5.2/5.8, and 2.4/2.7 nmol/l, respectively, and were negatively correlated to BMI. Total secretion of cortisol was higher than in healthy children. Cortisol concentration was independent of allergy, headache and ethnicity, CONCLUSION: In healthy children, salivary cortisol concentration was dependent on time, age and menarche. In children with RAP of psychosomatic origin, morning and total secretion of cortisol were significantly higher than in healthy children and negatively correlated to BMI.     

Pubertal development in children born small for gestational age

Reduced fetal growth appears to be associated with precocious adrenarche, early puberty and polycystic ovary syndrome with subsequent fertility problems. We investigated pubertal development and DHEAS levels in children born small for gestational age (SGA) and children born appropriate for gestational age (AGA). Physical examination was carried out twice. Mean age (+/-SD) at the first visit: SGA group, 9.1+/-1.1 yr; AGA group, 9.0+/-1.1 yr. AT FOLLOW-UP: SGA group, 11.6+/-1.0 yr; AGA group, 11.6 +/-1.1 yr. Pubertal stages of the children were assessed. Pubic hair was recorded as a measure of androgenization. Chronological age (CA) was expressed as a percentage of the age corresponding to the pubertal stage (CA/pubertal age [PA] x 100%). Estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) were measured in all children. FIRST VISIT: All children were prepubertal without signs of pubarche. DHEAS concentrations were higher in SGA children than in AGA children (p = 0.004). FOLLOW UP: Twenty SGA children and 15 AGA children were pubertal. CA/PA x 100% was lower in SGA girls than in AGA girls (p = 0.004). Since 2.5 years earlier all girls had been prepubertal, this means a more rapid progression in the SGA girls. CA/PA x 100% was similar in SGA and AGA boys (p = 0.1). DHEAS levels tended to be higher in SGA children than in AGA children (p = 0.06). These data support that a low birth weight may have long-lasting effects on pubertal development, as observed in a more rapid progression in SGA girls. In prepubertal SGA children, an exaggerated adrenarche is observed compared to AGA children, which tended to persist through puberty.     

Treatment of central precocious puberty with an LHRH analog. Effect on growth and bone maturation after 2 years of treatment

Eighteen children (15 girls and 3 boys) with true precocious puberty have been treated with an LHRH analogue (HOE 766, Buserelin suprefact) given subcutaneously during one (n = 11) or two (n = 7) years. Six of 18 children had organic precocious puberty, but their responses to therapy did not show any difference. A satisfactory suppression was achieved in 16 cases with plasma testosterone below 0.5 ng/ml (boys) or estradiol below 25 pg/ml and vaginal maturation index below 35 (girls). The mean annual height gain diminished from 9.5 +/- 0.8 cm during the control year to 7.7 +/- 0.7 cm and 5.1 +/- 0.7 cm during the first and second years of therapy respectively (p less than 0.05). Simultaneously, the mean bone age of 10.4 +/- 0.4 yr at onset of treatment, was 11.4 +/- 0.4 yr after one year and 11.8 +/- 0.3 yr after two years. These changes explain an average increase of predicted height of 5.7 cm after two years of treatment with the LHRH analogue. At least on the basis of these data with two years follow-up, this treatment seems satisfactory. We did not find anti-Buserelin antibodies in any of these patients.     

Somatomedin-C in accelerated growth of children with precocious puberty

To assess the role of somatomedin-C as a possible mediator of the growth spurt in children with central precocious puberty, we compared Sm-C levels in 40 children with central precocious puberty, 87 age-matched normal children, and 110 normal pubertal controls. Somatomedin C levels were significantly elevated for age in the children with precocious puberty (P less than 0.01), and were similar to the levels observed during normal puberty. The patients with precocious puberty were given the luteinizing hormone releasing hormone analogue D-Trp6-Pro9-NEt-LHRH (LHRHa) for 6 months. Treatment caused a significant decrease in secondary sexual characteristics, growth rate, plasma gonadotropins, sex steroids (estradiol in the girls and testosterone in the boys), and Sm-C levels. Growth during LHRHa treatment returned to the age-appropriate rate, whereas plasma Sm-C levels, although lower than pretreatment levels, remained significantly elevated for age (P less than 0.002). In addition, growth rates before and during treatment did not correlate with the plasma somatomedin C levels, nor did the decreases in growth rate during LHRHa therapy correlate with the decreases in somatomedin C levels. Growth rates did correlate significantly, however, with plasma estradiol levels in the girls (P less than 0.0005) and with plasma testosterone levels in the boys (P less than 0.025). We conclude that the growth spurt in children with precocious puberty cannot be explained by the plasma level of somatomedin C.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Sleep-related gonadotropin rhythms in children following treatment of acute leukemia: recovery of the hypothalamo-pituitary-gonadal axis after chemotherapy and CNS-irradiation

Twelve children (5 girls and 7 boys, between the ages of 6 and 20 years) in complete remission from previous ALL who had completed their entire anti-leukemic treatment program and who had been off all chemotherapy for at least one year, were included in a study of sleep-related prolactin and gonadotropin rhythms. All the patients had received prophylactic CNS-irradiation. The patients in early puberty showed a sleep-dependent FSH rhythm. Patients in middle-to-late puberty had sleep-related FSH and LH rhythms, and estradiol and testosterone plasma concentrations were normal for their pubertal stage, suggesting recovery of the hypothalamo-pituitary-gonadal feedback system. We conclude that the neuro-endocrine axis is not permanently injured by CNS-irradiation and anti-leukemic therapy.     

Precocious and premature puberty associated with treatment of acute lymphoblastic leukaemia.

Early puberty in 28 children (23 girls, five boys) treated for acute lymphoblastic leukaemia (ALL) at a mean age of 4.0 years (range 1.4-7.8) is described. All but one had received prophylactic cranial irradiation (1800-2400 cGy) and three children had received additional cranial or craniospinal irradiation as treatment for relapse of their leukaemia. Mean age for the onset of puberty was 8.8 (SD 0.8) years in the girls and 9.3 (0.8) years in the boys; this is greater than two standard deviations from the mean for normal girls and boys. Five children (three girls, two boys) had precocious puberty. The onset of puberty occurred at greater than two standard deviations from the mean for normal girls and boys in 14(13%) girls and 4(3%) boys treated at less than eight years of age between 1970 and 1985. In a group of 55 girls treated for ALL who had survived in first remission for six years or more from diagnosis, there was a relation between young age at onset of treatment and early menarche. We suggest that premature activation of the hypothalamic-pituitary-gonadal axis occurs as a consequence of hypothalamic dysfunction due to cranial irradiation. Precocious and premature puberty in children treated for ALL may be an important factor in contributing to short stature.     

SLEEP-RELATED GONADOTROPIN RHYTHMS IN CHILDREN FOLLOWING TREATMENT OF ACUTE LEUKEMIA: RECOVERY OF THE HYPOTHALAMO-PITUITARY-GONADAL AXIS AFTER CHEMOTHERAPY AND CNS-IRRADIATION

ABSTRACT. Twelve children (5 girls and 7 boys, between the ages of 6 and 20 years) in complete remission from previous ALL who had completed their entire anti-leukemic treatment program and who had been off all chemotherapy for at least one year, were included in a study of sleep-related prolactin and gonadotropin rhythms. All the patients had received prophylactic CNS-irradiation. The patients in early puberty showed a sleep-dependent FSH rhythm. Patients in middle-to-late puberty had sleep-related FSH and LH rhythms, and estradiol and testosterone plasma concentrations were normal for their pubertal stage, suggesting recovery of the hypothalamo-pituitary-gonadal feedback system. We conclude that the neuro-endocrine axis is not permanently injured by CNS-irradiation and anti-leukemic therapy.     

Changes of serum allopregnanolone levels in the first 2 years of life and during pubertal development.

Allopregnanolone is the best characterized among neurosteroids, and its role in the control of neuroendocrine axes has attracted increasing interest recently. However, there is no available information about circulating levels of allopregnanolone during infancy, childhood and puberty. We studied two groups of children: 1) those aged between 0 and 2 y (n = 72), and 2) those aged between 6 and 18 y, at different Tanner's stages (n = 82). In each of these patients, serum allopregnanolone, progesterone, cortisol, and dehydroepiandrosterone levels were evaluated after informed consent; allopregnanolone was measured by RIA after acid extraction on cartridge. There was no significant variation of serum allopregnanolone levels either in male and female children during the first 2 y of life. Furthermore, although serum dehydroepiandrosterone levels showed a significant decrease, inversely correlated with age of the children (p < 0.01), serum cortisol and progesterone levels showed a significant age-related increase during the first 2 y of life. Cortisol and allopregnanolone levels were positively correlated (p < 0.01). During puberty, we observed a progressive increase in serum allopregnanolone levels in both boys and in girls, which were higher at Tanner' s stage IV-V (0.7+/-0.01 nM; mean +/- SEM) than at stages I-II (0.32+/-0.02 nM; p < 0.01); mean levels were significantly higher at puberty than in the first 2 y of life (p < 0.01). Furthermore, during puberty, serum progesterone and dehydroepiandrosterone levels also increased progressively with age in both boys and girls. Allopregnanolone and dehydroepiandrosterone levels were positively correlated throughout puberty. The present results indicate that serum allopregnanolone levels do not change during the first 2 y of life but increase during pubertal development, suggesting that this steroid may be involved in the adaptive neuroendocrine mechanisms related to puberty.     

Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.     

The urinary C-peptide excretion in normal healthy children

The 24 h urinary C-peptide excretion was determined in 137 normal healthy children, 52 girls and 85 boys, 3-15 years of age. No significant difference was found between boys and girls. Median value of urinary C-peptide for boys and girls was 0.24 nmol/kg/24 h with a range of 0.07-0.61 nmol/kg/24 h. Urinary C-peptide correlated positively and significantly with age, weight, height, body surface area and the 24 h urinary creatinine excretion. Since the values of C-peptide excretion were not normally distributed they were log transformed and plotted against body weight. The linear regression and the 95% confidence limits were then calculated. Girls at puberty, 11-15 years of age, had significantly higher C-peptide excretion per kg body weight and per body surface area than younger girls, 3-10 years of age. Boys 13-15 years of age had significantly higher C-peptide excretion per body surface area than younger boys, 5-12 years of age. This indicates that children during the maximal growth spurt have an increased insulin secretion as measured by urinary C-peptide per body surface area.     

Serum procollagen I carboxyterminal propeptide (PICP) levels through puberty: relation to height velocity and serum hormone levels

The synthesis of type I collagen, the major component of the organic bone matrix, is reflected by procollagen I carboxyterminal propeptide (PICP) levels. Conflicting reports have been made about the relationship between PICP levels and puberty. We have studied PICP levels in serum in relation to pubertal stage, height velocity, oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, insulin-like growth factor I and growth hormone levels in 32 healthy boys aged 7.2–15.8 years and 32 healthy girls aged 7.2–14.8 years. The PICP levels in girls tended to be higher during midpuberty; in boys the levels were higher at the end of puberty. The PICP levels correlated strongly with height velocity in boys and girls. In conclusion, PICP correlates especially with height velocity. The variation of PICP between subjects during puberty is considerable. The PICP levels may predict growth at a certain moment, especially in cases where only one height measurement is available.     

Correlation of sex steroids with IGF-1 and IGFBP-3 during different pubertal stages

Insulin-like growth factor 1 (IGF-1) is the major factor that affects linear bone growth. Also, androgens and estrogens are necessary for increasing longitudinal bone growth during sexual maturation. The aim of this study was to investigate the relationships among IGF-1 axis and sex steroids during pubertal development in healthy adolescents. In this cross-sectional study, IGF-1, IGF binding protein-3 (IGFBP-3) and sex steroid levels (estradiol in girls, testosterone in boys) of 205 healthy adolescents (101 female, 104 male) aged 9-17 years were measured. All subjects were apparently healthy, with no growth retardation and with skeletal ages appropriate for chronological ages, and none were taking medications known to influence calcium homeostasis. Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist was used for determination of skeletal ages. Tanner's classification was used to determine the pubertal developmental stage. Fasting blood samples were obtained from subjects between 09:00-10:00 h. Serum IGF-1 and IGFBP-3 levels differed significantly between pubertal developmental stages. Serum IGF-1 levels and IGF-1/IGFBP-3 ratios increased with proceeding stages and maximum mean values were found at stages III-IV in girls and at stage IV in boys. Estradiol levels of girls and testosterone levels of boys differed significantly between stages, and in both sexes, serum IGF-1 levels and IGF-1/IGFBP-3 ratios were significantly correlated with sex steroid levels. Increase in growth hormone secretion increases IGF-1 levels. Furthermore, increasing sex steroids with pubertal development increase the IGF-1 levels and IGF-1/IGFBP-3 ratios that affect bone growth.     

The interaction of obesity and puberty on substrate utilization during exercise: a gender comparison

The study evaluated the interactions of puberty and obesity on substrate oxidation of overweight girls (n = 38) and boys (N = 35; BMI > 85th percentile) matched for gender, age, and puberty (pre/pubertal) with normal weight girls and boys. Metabolic rates (VO(2)) were obtained during rest and at 4, 5.6 and 8 k/h. Carbohydrate oxidation rates (mg/kgFFM/min) adjusted for % predicted VO(2max), were higher for prepubertal OW children than pubertal children (p < .03). Fat oxidation rates were higher for NW prepubertal boys compared with other boys. Results indicate that OW children, regardless of gender or pubertal status, increase their carbohydrate oxidation rate to compensate for higher than normal metabolic rates. The effects of obesity on the substrate use is marginally related to puberty.     

Growth response, pubertal growth and final height in Greek children with growth hormone (GH) deficiency on long-term GH therapy and factors affecting outcome

The growth data of 156 children (100 boys, 56 girls) with growth hormone deficiency (GHD), treated with human growth hormone (GH) for 5.7+/-3.7 years, from 1970-1997, were retrospectively analyzed to assess the efficacy of GH treatment and the factors involved. 62.2% of the studied population had idiopathic GHD (IGHD) and 35.2% had organic GHD (OGHD). At initiation of treatment, chronological age (CA) was 10.1+/-4.0 years in children with IGHD and 9.7+/-4.0 years in those with OGHD, while bone age (BA) was 7.0+/-3.7 and 7.7+/-3.2 years, respectively. The SDS of the growth velocity during the first year of therapy (GV1) was negatively related to CA at start of therapy (r = -0.53, p = 0.01). 109 children have reached final height (FH): 67 boys (FH = 165.3+/-6.3 cm) and 42 girls (FH = 153.9+/-5.4 cm). FH SDS was not significantly different from target height (TH) SDS. In the total group, FH SDS was positively related to height SDS for CA and BA at start of therapy (p = 0.01, p = 0.001, respectively), to TH SDS (r = 0.40, p = 0.001), and to GV1 (r = 0.33, p = 0.001). TH SDS was not different between the IGHD and OGHD groups (-1.02+/-0.8 vs. -0.94+/-6.9). The height gain at puberty did not differ between the groups with induced or spontaneous puberty in boys (23.7+/-8.6 vs. 25.4+/-6.9, not significant), while in girls it was higher in the group with spontaneous puberty (12.7+/-7.3 vs. 20.0+/-9.0, p = 0.008). The age and height at start of puberty was higher in girls and boys with induced puberty. In the total group, the FH SDS of children with induced puberty was higher in comparison with those with spontaneous puberty (-1.0+/-0.8 vs. -1.7+/-0.9, p = 0.001) and it was positively related to the height at start of puberty. When the two sexes were analyzed separately, the difference reached significance only in boys. In conclusion, children with GHD on GH treatment achieved a final height which was comparable to their genetic potential. The FH of children with OGHD was not different from those with IGHD. The age and height at start of puberty were the most significant determining factors for FH. Hence, a better FH might be expected by delaying or arresting puberty.     

The Urinary C-Peptide Excretion in Normal Healthy Children

ABSTRACT. The 24 h urinary C-peptide excretion was determined in 137 normal healthy children, 52 girls and 85 boys, 3–15 years of age. No significant difference was found between boys and girls. Median value of urinary C-peptide for boys and girls was 0.24 nmol/kg/24 h with a range of 0.07-0.61 nmol/kg/24 h. Urinary C-peptide correlated positively and significantly with age, weight, height, body surface area and the 24 h urinary creatinine excretion. Since the values of C-peptide excretion were not normally distributed they were log transformed and plotted against body weight. The linear regression and the 95% confidence limits were then calculated. Girls at puberty, 11–15 years of age, had significantly higher C-peptide excretion per kg body weight and per body surface area than younger girls, 3–10 years of age. Boys 13–15 years of age had significantly higher C-peptide excretion per body surface area than younger boys, 5–12 years of age. This indicates that children during the maximal growth spurt have an increased insulin secretion as measured by urinary C-peptide per body surface area.