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Background: Growth disorders are commonly observed in children with chronic inflammatory disease. It is likely that these disorders are mediated by a combination of factors, including the disease process and its treatment (with drugs such as glucocorticoids [GCs]). These factors affect the growth hormone-insulin-like growth factor I (IGF-I) axis, which is crucial for promoting linear growth at the level of the growth plate. Recent advances in our knowledge of the effects of GCs and proinflammatory cytokines on the growth plate have led to an improved understanding of the biological rationale for the use of growth-promoting therapy in children with chronic inflammatory disease and concurrent growth retardation., Conclusions: Both GCs and proinflammatory cytokines can adversely affect a number of components of growth plate chondrogenesis, and these effects can be ameliorated by raising local IGF-I exposure. However, this intervention does not lead to complete normalization of the growth plate. In children with chronic inflammation, the cornerstone of improving growth remains the judicious use of GCs while ensuring effective control of the disease process., (Copyright 2009 S. Karger AG, Basel.)

Background: Late presentation of congenital adrenal hyperplasia as a 46,XX disorder of sex development due to 11-beta hydroxylase deficiency is uncommon. Such a case raises issues regarding appropriate investigation and management., Case History: A 5-year-old boy who had recently moved to the United Kingdom presented at the endocrinology clinic with recurrent abdominal pain. He was normotensive and had a history of ambiguous genitalia since birth, a relatively small penis, bilateral cryptorchidism and pubic hair. A systematic workup revealed low anti-Mullerian hormone levels for age and sex and elevated serum testosterone, androstenedione and deoxycortisol levels. A urinary steroid profile confirmed a diagnosis of 11-beta hydroxylase deficiency. The child's karyotype was 46,XX. Further genetic analysis revealed a compound heterozygote mutation in the CYP11B1 gene. Ultrasound scan showed evidence of Mullerian structures and accumulation of menstrual blood in the vagina (haematocolpos). Following discussion at a multidisciplinary clinic, the patient did not undergo sex reassignment and subsequently proceeded to surgery for removal of the Mullerian structures., Conclusions: This case emphasizes the importance of a systematic approach to investigation of older children presenting with apparent male undermasculinisation. It also raises important issues about gender reassignment in mid-childhood and the indications for removal of Mullerian organs in a 46,XX boy., (Copyright 2009 S. Karger AG, Basel.)

Introduction: There is a scarcity of data on height as well as bone densitometry in humans with NOGGIN mutations., Methods: In 2 families with symphalangism, anthropometry, bone densitometry and genetic analysis of the NOGGIN gene were performed., Results: In family A, the height standard deviation scores of the affected father and son were -0.4 and 3.5, respectively. In family B, the height standard deviation scores of the affected father, twin daughters and another daughter were 1.7, 1.8, 2.4 and 1.8, respectively. In the children, percentage predicted bone mineral content (BMC) for height at the appendicular sites (total femur, femoral neck) was lower than at an axial site lumbar spine. In the 2 fathers, median bone mineral density at total femur and femoral neck was -0.3 standard deviation scores (-0.7, 0.2) and at lumbar spine the scores were -0.4 and 0.9. The children had median tibial and radial speed of sound velocities of -2.1 (-0.9 to -6.4) and -1.4 (-0.2 to -4.9), respectively. DNA analysis revealed a novel missense mutation in family A and family B, resulting in a Met190Val substitution and a Pro42Arg substitution, respectively., Conclusion: Heterozygous gene mutations in NOGGIN are associated with tall stature in children but not necessarily in adults. The appendicular BMC and speed of sound may be low in affected children but normalises by adulthood. However, axial BMC seems normal in childhood and is high in adulthood., ((c) 2008 S. Karger AG, Basel)

Background: Growth in children with inflammatory bowel disease (IBD) is affected through a number of mechanisms; controlling disease activity and supporting poor nutritional status are paramount in these patients. Further understanding of the basic mechanisms by which cytokines influence growth will facilitate the development of therapeutic modalities to improve growth., Conclusions: Clinical management that addresses growth and puberty in children with IBD should be a partnership between paediatric gastroenterologists and endocrinologists. Well-designed studies of growth-promoting hormonal treatment may answer questions regarding the efficacy and safety of treating growth retardation in the subgroup of patients who continue to fail to grow despite optimal management of their IBD., (Copyright (c) 2007 S. Karger AG, Basel.)

Background/aims: Klinefelter's syndrome is characterized by progressive testicular failure causing aspermatogenesis and androgen deficiency. Klinefelter patients classically have complete male sex differentiation, and genital anomalies are generally not recognized as associated features of the syndrome., Methods: We reviewed the cases of Klinefelter's syndrome with genitalia abnormalities from the Cambridge Disorders of Sex Development Database, and also reviewed previous case reports of genital anomalies associated with Klinefelter's syndrome and its variants., Results: We present seven Klinefelter patients with abnormalities of the genitalia, ranging from mild anomalies (chordee) to moderate undervirilisation (bifid scrotum and perineal hypospadias). Two cases were true hermaphrodites with karyotypes 47,XXY and 47,XXY/46,XX respectively. Though androgen insensitivity has been postulated previously as a possible pathogenic mechanism, we demonstrated normal androgen binding in 3 cases in which this was studied. Review of other case reports revealed a range of mild-to-severe abnormalities as well as cases reported as sex reversal, testicular feminization, and true hermaphroditism., Conclusion: Genital anomalies are not commonly observed in Klinefelter's syndrome. However, it is important to acknowledge the association, and recognize Klinefelter's syndrome as one of the causes of abnormal genitalia at birth., (Copyright 2007 S. Karger AG, Basel.)

Objectives: To assess stature and skeletal disproportion in children with chronic renal disease., Methods: Cross-sectional study of height (HT), sitting height (SH), subischial leg length (SILL), sitting height/height ratio (SH:HT) and disproportion score (SH SDS minus SILL SDS) in 56 children (M:35) with median age 11.4 years (range 4.5,18.7) with chronic renal disease., Results: There were 19 children with chronic renal insufficiency, 6 receiving peritoneal dialysis and 31 after renal transplant. The median HTSDS for the whole group was -1.21 (-2.8, 0.35). The median SH:HT ratio in non-transplanted children and renal transplant were 0.51 (0.49, 0.53) and 0.50 (0.48, 0.53), respectively (p = 0.02). The median disproportion score of the whole group was -3.2 (-4.8, -1.8). There was a significant correlation between disproportion score and SH:HT (r = 0.5, p = 0.005). SH:HT ratio was negatively related to duration of illness (r = 0.4, p = 0.005)., Conclusion: Children with chronic renal disease have significant body disproportion and this may be due to a disproportionately greater effect of disease and treatment on spinal growth., (Copyright 2003 S. Karger AG, Basel)

In order to study the short-to medium-term effects of cytotoxic chemotherapy (CT) for acute lymphoblastic leukaemia (ALL) on growth in prepubertal children, a prospective study of weight (Wt), height (Ht), sitting height (SH) and body mass index (BMI) was performed in 31 children receiving intensive CT for ALL. Two pubertal children, 1 child with Down's syndrome and 3 children who had cranial irradiation were excluded from the analysis. Monthly measurements were presented as change in standard deviation scores from baseline (delta SDS). The median age at diagnosis was 4.4 years (range, 1.1-14). The median duration of study per subject was 18 months (3-24). The median delta SDS-Ht reached a nadir of -0.35 at 6 months after the start of CT (p = 0.001, Wilcoxon signed rank test); the median delta SDS-SH was -0.55 at 3 months (p = 0.02); the median delta SDS-Wt and delta SDS-BMI increased at 2 months to 0.15 (p = 0.03) and 0.5 (p = 0.002), respectively. The median delta SDS-BMI was also elevated at 10 months (0.75, p = 0.01) reflecting the relative delay in recovery of Ht-SDS in comparison to Wt-SDS. The median SH:Ht ratio, a measure of disproportion, was reduced at 3 months (delta SH:Ht ratio, -0.01, p = 0.009). No significant changes in Ht-SDS, BMI-SDS or SH:Ht from baseline were evident at the end of the CT. Cytotoxic CT for ALL in childhood has a significant adverse effect on growth, but there is some evidence for recovery before the end of CT.

To investigate any association between changes in lower leg length (LLL) and urinary growth hormone (uGH) excretion, 4 prepubertal children supplied daily 12-hour overnight urine samples and had daily knemometry performed for 4 weeks. The mean daily and weekly LLL velocity (LLLV) of the group was (0.08 mm/day (95% CI 0.01-0.18) and 0.52 mm/week (range 0.38-0.78), respectively. The mean uGH excretion was 8.9 ng/l (CI 3.7-13.3), and the mean intrasubject coefficient of variation of uGH was 55% (range 32-93). The tallest subject who also had the highest LLLV excreted the least amount of uGH (mean 3.7 ng/l, CI 2.9-4.5). No temporal relationship was evident between daily uGH excretion and LLLV. There was no evidence of any association between amount of uGH excreted and LLLV. There remains some doubt on the usefulness of uGH measurement as the sole predictor of normal GH production.

Three studies to evaluate procollagen type I C-terminal propeptide, type I collagen cross-linked telopeptide and bone alkaline phosphatase (BALP) in the assessment of bone turnover and growth in children are presented. (1) In 50 short normal children treated with placebo or growth hormone, delta BALP after 3 months of treatment was highly correlated with height velocity response after 1 year (r = 0.67, p < 0.0001). (2) In 12 children with acute lymphoblastic leukaemia, marked changes in collagen peptides, BALP, and lower leg length velocity were seen during the first 6 months of chemotherapy. Suppression occurred during induction and the two intensification phases, with catch-up during the intervening phase (paired t-tests, p < 0.001). (3) Fourteen babies (birthweight < 1,500 g) treated with high-dose dexamethasone for bronchopulmonary dysplasia were compared with 25 non-steroid-treated babies < 1,500 g. Both collagen peptides decreased rapidly and dramatically (mean decreases 41-68%) after dexamethasone was started, accompanied by weight loss and lower leg shrinkage and followed by recovery during steroid weaning.