Median Bone Age Research Articles

Long-term follow-up data of patients with Multiple Pituitary Hormone Deficiency

To present the diagnosis processes, clinical findings, and long-term follow-up of patients with MPHD. Between 1999 and 2015, patients diagnosed with MPHD were evaluated. Clinical presentation, anthropometry, imaging studies, and clinical evolution were analyzed. Hormone status was evaluated, including growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone/luteinizing hormone (FSH/LH), and prolactin (PRL). Data were assessed using the student's t-test and the Mann-Whitney U test. Spearman's correlation was used for correlations. A p-value < 0.05 was considered statistically significant. Forty-five patients were included; 55.6% were male, the mean age at presentation was 5.6 ± 3.9 (0-14.4) years, and the median bone age was 3.5 ± 2.3 (0.5-11) years. At admission, GH deficiency was found in 88.9% of the cases, TSH deficiency in 77.8%, ACTH deficiency in 33.3%, FSH/LH deficiency in 22.2%, and PRL deficiency in 17.8%. During the follow-up, 62% of the cases added other hormone deficiencies. The mean follow-up period was 9.18 ± 3.6 (3.02-17.2) years. Patients with MPHD have very different clinical presentations, with GH and TSH deficiency being the most common in this study. Additional hormonal deficiencies can occur even years after the initial diagnosis and our results demonstrate that genetic height potential is achieved with GH treatment.

Simultaneous anterior cruciate ligament reconstruction and implant-mediated guided growth to correct genu valgum in skeletally immature patients

ObjectivesAdolescents with anterior cruciate ligament (ACL) tears can present with concomitant lower extremity coronal plane angular deformity (CPAD) that both predispose to injury as well as may increase the risk of graft rupture following ACL reconstruction (ACLR). The goal of this study was to examine the safety and efficacy of concomitant ACLR with implant-mediated guided growth (IMGG) compared to isolated IMGG procedures in paediatric and adolescent patients. MethodsOperative records of all paediatric and adolescent patients (age ≤ 18 years) that underwent simultaneous ACLR and IMGG by one of two paediatric orthopaedic surgeons between 2015 and 2021 were retrospectively reviewed. A comparison cohort of isolated IMGG patients was identified and matched based on bone age within one year, sex, laterality, and fixation type (i.e. transphyseal screw vs. tension band plate and screw construct). Pre- and post-operative mechanical axis deviation (MAD), angular axis deviation (AAD), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were recorded. ResultsA total of 9 participants who underwent concomitant ACLR and IMGG (ACLR ​+ ​IMGG) were identified, with 7 of these participants meeting the final inclusion criteria. The participants had a median age of 12.7 (IQR ​= ​12.1 – 14.2) years and median bone age of 13.0 (IQR ​= ​12.0 – 14.0) years. Of the 7 participants that underwent ACLR and IMGG, 3 underwent a modified MacIntosh procedure with ITB autograft, 2 received quadriceps tendon autograft, and 1 underwent hamstring autograft reconstruction. There were no significant differences in the amount of correction obtained between ACLR ​+ ​IMGG and matched IMGG subjects with respect to any measurement variable (MAD difference: p ​= ​0.47, AAD difference: p ​= ​0.58, LDFA difference: p ​= ​0.27, MPTA difference: p ​= ​0.20). There were also no significant differences in alignment variables per unit time between cohorts (MAD/month: p ​= ​0.62, AAD/month ​= ​0.80, LDFA/month ​= ​0.27, MPTA/month ​= ​0.20). ConclusionThe results of the current study indicate that concomitant ACLR and lower extremity CPAD correction is a safe approach to treat CPAD concomitantly with ACLR in young patients who present with an acute ACL tear. Furthermore, one can expect reliable correction of CPAD after combined ACLR and IMGG, no different than the correction obtained in the setting of IMGG alone. Level of evidenceIII.

Early onset of puberty during COVID-19 pandemic lockdown: experience from two Pediatric Endocrinology Italian Centers.

During COVID-19 pandemic lockdown, reports of evaluations for suspected precocious puberty significantly raised. We aimed to assess the increase of precocious puberty in patients referred to Pediatric Endocrinology Units of Brescia (Italy), to determine clinical characteristics of patients undergoing a GnRH stimulation test before and during lockdown and evaluate the role of environmental factors in pubertal development. Clinical and biochemical data of patients undergoing GnRH stimulation test were collected and stratified intwo groups: March 2019- February 2020 (Period 1) and March 2020- February 2021 (Period 2). A total number of 391 evaluations for suspected precocious puberty were identified in the two study periods: 183 (46.8%) first visits during Period 1, and 208 (53.2%) in Period 2. Sixty-one patients underwent a GnRH stimulation test (4.1% of first consultations) before the SARS-CoV2 pandemic, and 93 children (8.7%) after the lockdown. Thirty-four new diagnoses of central precocious puberty were registered during Period 1 (2.3%), vs. 45 new cases (4.2%) in Period 2. During lockdown patients evaluated for suspected precocious puberty underwent a stimulation test at younger age than those evaluated before pandemic (median age of 8.2 years vs. 8.4, p=0.04). In Period 2, children showed a median bone age advancement of 0.61years vs. 1.06 of Period 1 (p=0.03). During the COVID-19 pandemic, we observed an increased proportion of consultations for suspected precocious puberty. These children showed lower bone ageadvancement than observed in pre-lockdown suggesting the influence of pandemic-related lifestyle changes onpubertal development.

Bone Mineral Density in Children with Congenital Adrenal Hyperplasia

Background: C Treatment in all forms of CAH includes lifelong replacement of steroids. Steroids have an impact on bone health in multiple ways and are known to cause osteoporosis when given in high doses or for a longer duration. Objective: To evaluate bone mineral density (BMD), using dual-energy X-ray absorptiometry (DEXA) scan in children with CAH taking long-term steroids presenting in the pediatric endocrinology ward of National Institute of Child Health, (NICH) Karachi, Pakistan. Materials and Methods: This cross-sectional study was performed at the Department of Pediatric Endocrinology, National Institute of Child Health, Karachi from October 2021 to July 2022. A total of 47 diagnosed cases of CAH taking steroids for more than 5 years were enrolled. Assessment of BMD was done using a DEXA scan. Lumbar spine BMD was done and Z-score was modified for height for age z-score. The dose of steroids and duration was calculated. Results: Out of 47 patients, low BMD was observed in 8 (17.02%) patients. Individuals with low BMD had significantly higher median duration, (p=0.017), dose (p=0.003), and median alkaline phosphate level (p=0.036),) but low median BMD value (p=0.009) and z score (p&lt;0.001) than normal BMD individuals. Although median bone age (p=0.009) was appropriate for chronologic age in low BMD patients. A moderate negative significant correlation was observed between z score and age (rho=-0.319, p=0.029), z-score and duration of steroid treatment (rho=-0.364, p=0.012), z score and alkaline phosphate (rho=-0.466, p=0.001), z score and bone age (rho=-0.378, p=0.009). Conclusion: Low BMD was observed in 17% of children on the DEXA scan. Moreover, these individuals had significantly higher median average duration and dose of hydrocortisone.

OR18-2 Clinical, Hormonal and Genetic Characterization of Familial Central Precocious Puberty

Abstract Context: Familial central precocious puberty (CPP) is a prevalent form (about 27.5%) of precocious puberty. Loss-of-function mutations in two maternally imprinted genes, MKRN3 and DLK1, were identified in families with CPP showing dominant autosomal inheritance with paternal transmission. Maternally transmitted CPP was previously demonstrated in up to 60% of families using pedigree analysis, however, no definitive genetic abnormality has been identified so far. Objectives To estimate the prevalence of familial cases in a multiethnic cohort with CPP. To characterize the genetic basis and the mode of inheritance of the affected families. To compare clinical and hormonal features of patients with familial CPP due to different modes of transmission. Patients and Methods Clinical and hormonal data were obtained from medical registries of 495 patients with CPP and no brain MRI alterations. Familial CPP was defined as the presence of one or more close relatives with CPP or precocious menarche (≤9 yr). Sanger sequencing of MKRN3 and DLK1 was performed in 427 index cases. Targeted gene panel sequencing was performed in 79 cases, while whole exome sequencing was performed in 101 cases from 36 families Results Among 495 index cases, 159 had familial CPP (31%). The mode of transmission of CPP was identified as paternal in 58 (35%), maternal in 59 (38%), indeterminate in 34 (22%), and both maternal and paternal transmission in 8 (5%). Most families with paternal or maternal transmission had 2 generations known to be affected (51 and 77%, respectively). Notably, 67% of index cases with maternally transmitted CPP had their mother affected. In girls with CPP, the median age of thelarche was 6.5 yr in the paternally transmitted group, 6.9 yr in the maternally transmitted group, and 7.3 yr in the indeterminate group (p= 0.547). Median bone age advancement was 2.1, 2.3 and 1.2 yr, respectively (p= 0.013). Basal LH levels were higher in girls with paternally transmitted CPP (p= 0.047). Among those with paternally transmitted CPP, MKRN3 and DLK1 mutations were identified in, respectively, 63.8% and 10.3% of the families. Conclusions A significant prevalence (31%) of familial CPP was demonstrated in a multiethnic cohort. Maternally transmitted CPP represented the most frequent form of familial CPP (38%). MKRN3 loss-of-function mutations were responsible for most paternally transmitted CPP cases (63.8%), followed by DLK1 loss-of-function mutations (10.3%). Presentation: Monday, June 13, 2022 11:15 a.m. - 11:30 a.m.

Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study.

PurposeRegarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings.MethodsA total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes.ResultsAs of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5–11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78).ConclusionsThis registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment.

Gonadotropin releasing hormone analog treatment in children with congenital adrenal hyperplasia complicated by central precocious puberty.

Congenital adrenal hyperplasia (CAH) can be complicated by central precocious puberty (CPP) in children, which may compromise final height. We aimed to evaluate the effect of gonadotropin-releasing hormone analog (GnRHa) therapy on growth in children with CAH. Twelve children with CAH were enrolled in a follow-up study. Eight patients underwent the GnRH stimulation test. GnRHa-treatment was administered at 3.75 mg every 4 weeks; the dose had to be increased to 7.5 mg in three patients. Bone age, growth velocities and body mass index of the patients were monitored during treatment. Median chronologic age and bone age at diagnosis were 6.8 (3.5) years and 11 (1.2) years, respectively. Median follow-up was 4.4 (4.9) years. A significant difference was found in the median ratio of bone age to chronological age between diagnosis and last visit (p=0.005) and between the beginning of GnRHa treatment and last visit (p=0.004). Median growth velocity was 4 (2.5) cm, 3.4 (5.2) cm and 5.5 (5.5) cm at the end of the first, second and third years of the therapy, respectively. Second-year growth velocity was inversely correlated with median bone age at diagnosis (rho:-0.758, p=0.004) and at the initiation of therapy (rho:-0.876, p<0.001). GnRHa therapy should be considered for augmentation of linear growth and diminishment of bone age advancement in children with CAH complicated by CPP, particularly in children who do not have extremely advanced bone age for chronological age.

Children ankle valgus deformity treatment using a transphyseal medial malleolar screw

Introduction Ankle valgus deformity is rare in children. It generally leads to difficulties wearing shoes, walking instability and mechanical pain. No medical treatment is effective and the only option is surgical correction of the deformity. Two main options are available: supramalleolar osteotomy and medial malleolar epiphysiodesis. We report our experience with epiphysiodesis using a transphyseal medial malleolar screw. Patients and methods This is a retrospective study of all children followed for ankle valgus and treated by transphyseal medial malleolar screw epiphysiodesis in our department. The study included 10 cases of ankle valgus deformity in seven children (four with multiple extostoses, two type 1 neurofibromatosis, one Larsen's syndrome) who completed skeletal maturity. At surgery, median bone age was 12 years (10 to 13 years and 6 months) and the median tibiotalar angle was 17.5° (10° to 30°). Results At skeletal maturity, preoperative valgus was corrected in six patients (9/10 ankles). The median tibiotalar angle was 5° (0° to 25°). Valgus was not corrected in one patient (30° to 25°). No postoperative complications occurred. Discussion Epiphysiodesis by transphyseal medial malleolar screw is a simple, efficient and safe procedure to correct a significant or symptomatic ankle valgus deformity in children before skeletal maturity. Level of evidence Level IV, retrospective study.

High Prevalence of Primary Ovarian Insufficiency in Girls and Young Women with Nijmegen Breakage Syndrome: Evidence from a Longitudinal Study

Nijmegen breakage syndrome (NBS) is a severe chromosomal instability disorder characterized by microcephaly, growth retardation, immune deficiency, and predisposition for malignancy. It is caused by hypomorphic mutations in the NBN gene, which product belongs to the protein complex critical for processing DNA double-strand breaks during mitotic and meiotic recombination. Data on gonadal function in patients with NBS are limited. Growth and sexual development, along with hormonal assays, were evaluated in girls and young women with NBS homozygous for c.657_661del5 mutation. The group comprised 37 girls and young women with NBS (ages, 0.17-24.25 yr), followed between 1993 and 2008. Patients were divided into three age groups: 1) 1-3 yr; 2) 4-9 yr; and 3) 10 yr and older. Growth, puberty, concentrations of gonadotropins and 17-beta-estradiol, bone age, and pelvic ultrasound were assessed. None of the patients presented a typical growth spurt; the adult height ranged between the 3rd and 25th centiles. Median bone age was delayed by 4.05 yr. Pubarche reached stadium P2 in eight patients and P3 in two patients. In all but one girl, thelarche did not exceed Th2, with low 17beta-estradiol levels. Gonadotropin levels showed a biphasic pattern, with median FSH values of 55.0, 10.9, and 81.9 IU/liter, and LH of 3.2, 0.8, and 21.0 IU/liter in consecutive age groups. Ultrasound visualized small ovaries or solid streaks and the hypoplastic uterus. Primary ovarian insufficiency and the associated hypergonadotropic hypogonadism are hallmark manifestations in girls and young women with NBS. Our findings emphasize the need for long-term endocrinological and interdisciplinary supervision of these patients.

Accelerated Escape from GH Autonegative Feedback in Midpuberty in Males: Evidence for Time-Delimited GH-Induced Somatostatinergic Outflow in Adolescent Boys

A single injected pulse of GH inhibits the time-delayed secretion of GH in the adult by way of central mechanisms that drive somatostatin and repress GHRH outflow. The marked amplification of spontaneous GH pulse amplitude in puberty poses an autoregulatory paradox. We postulated that this disparity might reflect unique relief of GH-induced autonegative feedback during this window of development. The present study contrasts GH autonegative feedback in: 1) normal prepubertal boys (PP) (n = 6; Tanner genital stage I, chronologically aged 8 yr, 9 months to 10 yr, 1 month; median bone age 8.5 yr); 2) longitudinally identified midpubertal boys (MP) (n = 6; Tanner genital stages III/IV, aged 12 yr, 6 months to 15 yr, 6 months; median bone age 15 yr); and 3) healthy young men (YM) (n = 6, aged 18–24 yr; bone age >18 yr). Subjects each underwent four randomly ordered tandem peptide infusions on separate mornings while fasting: i.e. 1) saline/saline infused iv bolus at 0830 h and 1030 h; 2) saline/GHRH (0.3 μg/kg iv bolus) at the foregoing times; 3) recombinant human (rh) GH (3 μg/kg as a 6-min square-wave iv pulse)/saline; and 4) rhGH and GHRH. To monitor GH autofeedback effects, blood samples were obtained every 10 min for 5.5 h beginning at 0800 h (30 min before GH or saline infusion). Serum GH concentrations were quantitated by ultrasensitive chemiluminometry (threshold 0.005 μg/liter). On the day of successive saline/saline infusion, MP boys maintained higher serum concentrations of: 1) GH (μg/liter), 2.2 ± 0.25, compared with PP (0.61 ± 0.10) or YM (0.88 ± 0.36) (P = 0.011); 2) IGF-I (μg/liter), 493 ± 49 vs. PP (134 ± 16) and YM (242 ± 22) (P < 0.001); 3) T (ng/dl), 524 ± 58 vs. PP (<20) (P < 0.001); and 4) E2 (pg/ml),19 ± 3 vs. PP (< 10) (P = 0.030) (mean ± sem). Consecutive saline/GHRH infusion elicited comparable peak (absolute maximal) serum GH concentrations (micrograms per liter) in the three study groups, i.e. 18 ± 5.0 (PP), 9.6 ± 1.7 (MP), and 14 ± 5.3 (YM) (each P < 0.01 vs. saline; P = NS cohort effect). Injection of rhGH attenuated subsequent GHRH-stimulated peak serum GH concentrations (micrograms per liter) to 7.8 ± 1.9 (PP), 5.8 ± 1.2 (MP), and 4.8 ± 1.1 (YM) (each P < 0.01 vs. saline; P = NS pubertal effect). GH autofeedback reduced non-GHRH-stimulated (basal) serum GH concentrations by 0.74 ± 0.28 (PP), 5.7 ± 1.7 (MP) and 1.4 ± 0.27 (YM) fold, compared with saline (P = 0.016 for MP vs. PP or YM). In addition to greater fractional autoinhibition, MP boys exhibited markedly accentuated postnadir escape (4.6-fold steeper slope) of suppressed GH concentrations (P < 0.001 vs. PP or YM). Linear regression analysis of data from all 18 subjects revealed that the fasting IGF-I concentration negatively predicted fold-autoinhibition of GHRH-stimulated peak GH release (r = −0.847, P = 0.006) and positively forecast fold-autoinhibition of basal GH release (r = +0.869, P < 0.001). In contrast, the kinetics of rhGH did not differ among the three study cohorts. In summary, boys in midpuberty manifest equivalent responsiveness to exogenous GHRH-stimulated GH secretion; heightened susceptibility to rhGH-induced fractional inhibition of endogenous secretagogue-driven GH release, compared with the prepubertal or adult male; and accelerated recovery of GH output after acute autonegative feedback. This novel tripartite mechanism could engender recurrent high-amplitude GH secretory bursts that mark sex hormone-dependent activation of the human somatotropic axis.

Intra-Uterine Growth Retardation (IUGR) and Silver-Russell Syndrome (SRS): Etiological Aspects and Some Auxological Characteristics of Their Post-Natal Short Stature

Intra-uterine growth retardation (IUGR) and Silver-Russell syndrome (SRS) are born short for gestational age and many of them do not show post-natal catch-up growth Although post-natal catch-up growth frequently occurs, significant number of both IUGR and SRS newborns often fail to catch up. This may result in very short adult height (more than 2 standard deviations (SD) below the mean) in up to 20% of these patients, in association with poor school and social performance.In order to try to induce catch-up growth and hopefully increase final height, attempts have been made in clinical trial to treat these growth hormone (GH) sufficient patients with human GH.Using the Kabi Pharmacia International Growth Study patient data base, a group of 106 IUGR (83 males and 23 females) and 45 SRS with persistent post-natal growth failure were studied. IUGR clinical characteristics included a birth length and weight more than 2 SD below the mean for gestational age. Height deficit at start of the GH treatment was -3.0 standard deviation scores (SDS) for chronological age (CA), at a median CA of 8.7 years with a median bone age (BA) of 7.0 years. Mean parental heights were 166 cm for fathers and 153 cm for mothers. Median dose of recombinant human GH (rhGH) in 106 IUGR patients was 0.5 IU/kg/week, given at a median frequency of 5 injections per week. The median height SDS for CA at the start and at 1, 2 and 3 years of hGH treatment were -3.0, -2.5, -2.1 and -1.9 respectively.45 patients presented with SRS. Their median CA and BA at start of treatment were 6.7 and 3.2 years respectively. Mean parental heights were 167.5 cm for fathers and 160 for mothers. Median dose of rhGH in these 45 SRS was 0.7 IU/kg/week, with a median frequency of 6 injections per week. Median height SDS of SRS patients at start, 1, 2 and 3 years of hGH treatment were -3.5, -2.9, -2.8 and -2.2 respectively. One difference between these IUGR and SRS groups is that SRS patients tended to be born of normal height parents, in contrast to IUGR with persistent post-natal growth failure. In these two groups, exogenous GH treatment tended to induce catch up growth, although long term follow up is sufficient to allow conclusions to be draw regarding these patients' final adult height.

Applicability of the Greulich and Pyle skeletal age standards to black and white children of today.

The Greulich and Pyle skeletal age atlas was derived from white children of upper socioeconomic level during the 1930s. To our knowledge, the Greulich and Pyle standards have not been reassessed for both black and white children; it was the purpose of this study to reassess the applicability of these standards to today's children. A "blinded" review of hand roentgenograms taken for the evaluation of trauma was performed. Age of the subjects was evenly distributed between 0 and 18 years. The roentgenograms were scored for bone age by five individuals from different disciplines and levels of training. The difference between the median bone age and the child's chronologic age was calculated for each roentgenogram and stratified into four age groups: early childhood (0 to 4 years), middle childhood (4 to 8 years), late childhood (8 to 13 years), and adolescence (13 to 18 years). The roentgenograms were obtained from four hospital emergency rooms in the Lake Erie basin area, the same geographic area from which the Greulich and Pyle standards originated. There were 841 children: 452 boys and 389 girls, 461 black and 380 white children. The bone ages and chronologic ages were similar for white girls of all ages. Black girls were skeletally advanced by 0.4 to 0.7 year (P < .001), except during middle childhood. White boys were skeletally delayed during middle childhood by 0.9 year (P < .001) and during late childhood by 0.4 year (P < .01), but they were advanced during the adolescent years by 0.5 year (P < .01). Black boys showed no difference except for the adolescent group, which was skeletally advanced by 0.4 year (P < .02). The Greulich and Pyle atlas is not applicable to all children today, especially black girls. We should be aware of this information when making clinical decisions requiring accurate bone ages.

Recombinant Human Growth Hormone Treatment in Short Children with Chronic Renal Disease, before Transplantation or with Functioning Renal Transplants: an Interim Report on Five European Studies

Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection.

Growth-stimulating effects of recombinant human growth hormone in children with end-stage renal disease

Because patients with uremia have evidence for growth hormone resistance, we investigated whether this resistance can be overcome by administration of recombinant human growth hormone in supraphysiologic doses in children with severe uremia. Nine stunted children with end-stage renal disease (median age 5.8 years, median bone age 2.7 years) were treated with recombinant human growth hormone, 4 IU/m2/day subcutaneously, for a period of 1 year. Median height velocity was increased from 4.4 cm/yr before therapy to 8.0 cm/yr during treatment. Negative values for height velocity standard deviation scores for chronologic age were improved from a median of -2.6 to +1.5 without advancing bone age more than chronologic age. The growth hormone-insulin-like growth factor I resistance may be explained in part by the increased serum concentration of the high molecular weight insulin-like growth factor binding protein despite normal insulin-like growth factor I serum concentration. Treatment with recombinant human growth hormone improved the ratio between the serum concentrations of insulin-like growth factor I and its binding protein, and normalized the somatomedin bioactivity in the growth cartilage bioassay.

Luteinizing hormone‐releasing hormone analogue (Buserelin) treatment for central precocious puberty: A multi‐centre trial

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Oestrogen treatment of constitutionally tall girls with 0.1 mg/day ethinyl oestradiol.

For the treatment of tall stature in girls, oestrogens are usually given in high doses. In this study, growth data of 35 constitutionally tall girls treated with only 0.1 mg/day ethinyl oestradiol (EE) are reported (Group 1). The data were compared with those of 23 untreated girls with comparable bone ages and growth potential (Group 2), and with those of 5 girls treated with 0.3 mg/day EE (Group 3). All groups were followed until cessation of growth. In group 1, the median bone age at the onset of treatment was 12.50 years (Greulich-Pyle, range 10.50-13.75), and the median height prediction was calculated to be 184.4 cm (Bayley-Pinneau, range 179.5-191.5). Following oestrogen treatment of 21 months duration (range 10-37) the median adult height was reduced by 4.3 cm (range 0.0-9.0), or 3.9 cm if corrected for the error of prediction in the control group. The effect was greater in those girls with bone ages below 12.5 years at the onset of treatment (6.7 cm/corrected value 7.4 cm) than in the older girls (4.2 cm/3.6 cm). In Group 2 (controls) the median final adult height was over-estimated by 0.4 cm (range-4.9 to 4.9), but was under-estimated by 0.7 cm in those girls with bone ages below 12.5 years. In girls of comparable bone age similar reductions were obtained whether 0.3 mg/day EE (Group 3) or 0.1 mg/day was given (4.4 vs. 4.2 cm). A comparison of these results with published data indicates that higher EE doses (0.3-0.5 mg/day) have only little, if any, greater effect on the growth of girls than the dosage of 0.1 mg/day EE used in this study.