Growth hormone secretory patterns in children with short stature

To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.     

Gender identity and sex-of-rearing in children with disorders of sexual differentiation

AIM: To compare declared sexual identity to sex-of-rearing in individuals with disorders of sexual differentiation. METHODS: All 84 patients > or =5 years old in a pediatric psychosexual development clinic were assessed for sex-of-rearing and sexual identity. Diagnoses included 1) male-typical prenatal androgen effects but an absent or severely inadequate penis - 45 patients with cloacal exstrophy or aphallia; 2) inadequate prenatal androgens and a Y-chromosome - 28 patients with partial androgen insensitivity (pAIS), mixed gonadal dysgenesis (MGD), hermaphroditism, or craniofacial anomalies with genital ambiguity; 3) inappropriate prenatal androgen effects and a 46,XX karyotype - 11 patients with congenital adrenal hyperplasia (CAH). RESULTS: Of 73 patients with disordered sexual differentiation and a Y-chromosome, 60 were reared female; 26 of the 60 (43%) declared female identity while 32 (53%) declared male identity including 18 (55%) with cloacal exstrophy, six (55%) with MGD, four (40%) with pAIS, one (50%) with aphallia, one (100%) with hermaphroditism, and two (67%) with craniofacial anomalies; two (3%) declined to discuss identity. Nine of 11 patients with CAH and a 46,XX karyotype were reared female and two reared male; six (55%) declared female identity and five (45%) declared male identity. Of 84 total patients, 69 were reared female, but only 32 lived as female, while 29 lived as male; four patients refused to discuss sex-of-living; parents of four patients rejected their declarations of male identity. All 15 patients reared male lived as male including two genetic females. CONCLUSION: Active prenatal androgen effects appeared to dramatically increase the likelihood of recognition of male sexual identity independent of sex-of-rearing. Genetic males with male-typical prenatal androgen effects should be reared male.     

Breathing patterns in prepubertal children with sleep-related breathing disorders

OBJECTIVE: To investigate abnormal breathing patterns during sleep in prepubertal children using nonstandard polysomnographic patterns in association with an apnea-hypopnea scoring technique. PATIENTS AND METHODS: Study participants included 400 children with suspected sleep-related breathing disorders and 60 control children. We analyzed clinical signs and symptoms at entry into the study and 3 months after otolaryngological treatment. We determined the frequency of predefined breathing patterns during sleep through blind analysis of polysomnograms obtained once in control subjects and twice in children referred to our clinic (before and after adenotonsillectomy), using the nasal cannula-pressure transducer system, mouth thermistor, esophageal manometry, microphone, and pulse oximetry. We also determined the relationship between breathing patterns during sleep and residual postsurgery symptoms. Further analysis was performed of symptoms and polysomnographic patterns in those children who underwent new treatment interventions due to persistence of symptoms and abnormal polysomnogram findings. RESULTS: Tachypnea, persistently elevated breathing effort, progressively increased breath effort, and discrete flattening of nasal airflow monitored with the nasal cannula-pressure transducer system without oxygen saturation decreases help determine disorder as much as apneas and hypopneas. Abnormal, nonstandard breathing patterns were associated with the same symptoms as those in children with apnea and hypopnea and were more commonly present when there was incomplete resolution of initial symptoms that led treating practitioners to request further treatment. CONCLUSION: Currently published polysomnographic scoring recommendations overlook common breathing abnormalities during sleep that are associated with clinical complaints.     

Quantitation of urinary gonadotropins in normal children

A simple and improved method for the quantification of urinary LH and FSH was developed. Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Urinary LH and FSH concentrated by ammonium sulfate were coeluted with an iodinated LH and FSH tracer. Gel chromatography of the urine revealed that the majority of immunoreactive LH and FSH were eluted coincident with 125I-LH and 125I-FSH. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Age-dependent changes in urinary LH excretion were significant in normal boys and girls 6-17 y of age. Urinary FSH excretion in these children did not change in an age-dependent fashion.     

Basal and hormone-induced urinary cyclic AMP in children with renal disorders.

The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.     

Serum levels of LH and FSH in patients with adreno-genital syndrome (AGS) (author's transl)]

Serum levels of LH, FSH, testosterone and 17beta-estradiol were estimated by radioimmunoassay in 13 children suffering from AGS. Hormone levels were determined during and after substitution therapy and were compared with values registered in normal subjects. After therapy was stopped a statistically significant rise of testosterone and 17beta-estradiol was observed, but no changes in the serum levels of LH and FSH was noted. The discrepancies between the two observations are discussed.     

Periungual capillaroscopy patterns in normal children]

In children as well as in adults, capillaroscopy is an unsophisticated and non invasive technique which allows to investigate vascular acrosyndromes and systemic diseases. We have studied nailfold capillaroscopy patterns in 80 children without over vascular or systemic disease: pericapillary halos and haemorrhages increased with age and capillaries matured towards the typical hair pin structure seen in adults. The number of minor dystrophies increased with age and the venous subpapillary plexuses became less easily visible.     

Quantitation of urinary growth hormone in children with normal and abnormal growth

Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.     

Increased LH and FSH secretion after cranial irradiation in boys

The effect of high-dose cranial- and craniospinal irradiation and chemotherapy on the gonadotropin-sex steroid axis was studied during different stages of puberty by measuring pulsatile secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. The patients were thirteen boys who had been treated for malignant brain tumor residing well away from the hypothalamo-pituitary region. The median time to follow-up was 9 (1–16) years. The onset of puberty was early in the patients, median 10.5 years, compared to the average age for Swedish boys, which is at median 12.4 years. There was, before puberty, no significant difference in LH and FSH secretion between patients and a control group of normal boys. In early, mid- and late stages of puberty, however, LH and FSH secretion was increased in the patients overall, whereas testosterone secretion was maintained within the normal range in spite of signs of gonadotoxocity with small testicular volumes. These results indicate that the vulnerable parts of the gonadotropin releasing hormone (GnRH)-gonadotropin (LH, FSH)-gonadal axis are the regulatory system that determines the timing of pubertal induction and the gonads. The GnRH-LH, FSH-releasing neurons appear relatively resistant to cranial irradiation as they are able to respond with supranormal LH and FSH levels for long periods of time after treatment. Med Ped Oncol 29:280–287, 1997. © 1997 Wiley-Liss, Inc.     

Guidelines for evaluating and managing children born with disorders of sexual development

Children born with disorders of sexual differentiation (DSD) pose numerous challenges for the parents, family, and treating physicians. The pediatrician is usually the first medical contact for newborns with DSD or for toddlers and children who present with DSD at a later time.Several years ago, we formed a Gender Medicine Team (GMT) at Baylor College of Medicine and Texas Children's Hospital (TCH) to explore and evaluate the most appropriate management strategies, which had long been a matter of concern and contention. Subsequently, the GMT, composed of experts in the fields of endocrinology, ethics, genetics, gynecology, psychology, pediatric surgery, and urology, formed a Task Force to evaluate the information available from our own experiences and from reviews of the literature. Utilizing the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system to assess the evidence and recommendations, the Task Force developed a consensus statement for clinical management of DSD and for making appropriate sex assignments.     

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.     

Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts

Results of single-dose therapy of urinary tract infections in pediatric patients have been contradictory mainly because of selection criteria. We evaluated the efficacy of a single dose of gentamicin in patients with normal urinary tracts and in whom urinary tract infections were recurrent. Twenty-one patients were included in the study, and a similar number in a conventional group given treatment for 10 days. Cure rate was 100% in both groups. The recurrence rates of 67% in the study and 52% in the conventional group were comparable. Single-dose therapy seems to have a role in the treatment of urinary tract infection in the absence of urinary tract malformation.     

Low urinary GH levels in normal statured obese children

Urinary GH (u-GH) levels were evaluated in 240 children (age range 5-14 years; 136M, 104F) of normal height (25-90th centile); 165 children were defined as "non-obese" (body mass index (BMI) < 75th centile for their chronological age (CA)) and 75 as "obese" (BMI > 75th). U-GH levels were determined using a two-site enzyme immunometric assay and calculated as the mean obtained from the values of three consecutive first morning voidings; results were expressed as both u-GH concentration (ng1⁻¹) and u-GH excretion (ng per night). Multiple regression analysis revealed that in all children (non-obese and obese) most of the variation in u-GH levels (ngl ¹ and ng night⁻¹) was explained by BMI (coefficient: −0.72, p < 0.0001 and coefficient: −0.10, p < 0.001, respectively) and chronological age (coefficient: 1.03, p < 0.01 and coefficient: 0.27, p < 0.001, respectively), whereas sex and pubertal stage did not add significance to the variance. In obese children, mean u-GH concentration and u-GH excretion (per night) levels were significantly lower than those recorded in non-obese children both before and during puberty. A similar trend towards higher u-GH levels at puberty was found in non-obese and obese children. In conclusion, our study shows that u-GH levels are (a) related to CA and BMI in the general population and (b) significantly lower in obese than in non-obese children, in spite of their comparable normal height. The measurement of u-GH excretion in the assessment of children with short stature needs to take into consideration the role of marked ponderal excess, which is associated "per se" with significantly lower u-GH levels.