M O Savage

..GH therapy, using doses similar to those approved for Turner syndrome (TS), induced short-term increases in height velocity over 1-3 years, and may improve final adult height with longer-term treatment...

..We discuss the current status of endocrine and molecular evaluation, focussing on the phenotypic characteristics of genetic defects in the GH-IGF-I axis...

..After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height...

..A protocol for investigation of the child with suspected Cushing's syndrome is presented followed by principles of management...

..Genetic analysis for single-gene defects has made enormous contributions to understanding the physiology of growth regulation. Can this type of investigation help in predicting growth responses to GH or IGF-I therapy?..

..GH therapy induces short-term increases in height velocity over 1-3 years, and is likely to improve adult height...

..The management of pediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life...

..The management of paediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life...

..We consider appropriate therapy for patients with abnormal auxology and subnormal adult height prognosis, highlighting new data to clarify therapeutic choices leading to optimal clinical outcome...

..Improved glycaemic control has been reported in type 1 and type 2 diabetes in adults. A therapeutic trial in naïve children with GHIS is currently under way...

..Quality of life does not appear to be decreased in adolescents with GHD who stop treatment, so achievement of satisfactory bone mass is a major determinant of the decision whether to continue therapy...

..In our experience, IGF-I is more sensitive to disturbance of GH action that IGFBP-3, however in severe GHIS cases, IGF-I is usually undetectable and measurement of IGFBP-3 is valuable as a guide to the severity of the biological defect...

..The management of paediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life...

..Collaboration between paediatric endocrinologists and other subspecialists will improve the opportunity for successful GH therapy. Treatment should be initiated before or during early puberty...

..Finally we discuss therapy with IGF-I within the limits of the USA Food and Drug Administration and European Medicines Agency labels for GH resistance...

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..Conclusion: Screening of the IGFALS is important in children with short stature associated with low serum IGF-I, IGFBP-3 and ALS...

..Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients...

..93 +/- 1.13, i.e. less (p = 0.005) than the difference between height SDS and target height SDS at presentation, i.e. 1.72 +/- 1.26, indicating long-term catch-up growth...

..Paediatric Cushing's disease is frequently associated with abnormal puberty. We addressed the hypothesis that prepubertal patients show excessive virilization and pubertal patients show suppression of LH and FSH secretion...

..Cushing's syndrome in childhood and adolescence is rare. We analysed the clinical presentation, investigation, management and therapeutic outcome in 12 paediatric patients with Cushing's syndrome...

..Design: We investigated the effect of the novel defect on mRNA splicing using an in vitro splicing assay and a cell transfection system...

..Although the short-term effects of pituitary RT are well documented, there are less data on possible long-term sequelae. We report the long-term anterior pituitary function in a cohort of paediatric CD patients treated with pituitary RT...

..Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD...

..This may predispose to clinically significant osteopenia in later adult life...

..03 (-0.53-0.38). These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable...

..We previously described four mildly affected GHI patients with an intronic mutation in the GHR gene (A(-1)-->G(-1) substitution in intron 6), resulting in the activation of a pseudoexon (6Psi) and inclusion of 36 amino acids...

..Disturbance of linear growth is an important feature of many patients with adrenal disorders in childhood. Assessment of its pathogenesis and careful management are necessary to ensure optimal final adult height...

..GH sensitivity, measured by IGF-I and IGFBP-3 responses in the IGF-I generation test, may reveal abnormalities in ISS, although it is likely that the dose of recombinant human GH and frequency of sampling in the test need to be modified...

..Psychosis secondary to paediatric Cushing's disease (CD) is extremely rare and presents a significant management challenge...

..17 (p<0.0001). CONCLUSIONS: Simple, accurate measurement of height and BMI SDS values provides a quick, and sensitive diagnostic discriminator in pediatric patients with CD or SO, thus potentially avoiding complex investigations...

..Collaboration between the paediatric and adult departments and an experienced radiotherapist contributed to the successful outcome of these two patients...

..We assessed factors contributing to skeletal maturation in patients with paediatric CD...

..There are few published comparisons between paediatric and adult-onset Cushing's disease (CD). We compare the epidemiology, diagnostic features and cure rate by transsphenoidal surgery (TSS) in these groups...

..We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1-29)NH2 (GHRHa) for a period of 12 months...

..It will probably be decided during the next decade whether use of IGF-I or the IGF-I-IGFBP-3 complex becomes firmly established as an accepted endocrine therapy...

..These findings suggest that this homozygous mutation affects 11beta-hydroxylase function, resulting in the clinical features of non-classical adrenal hyperplasia in this family...

..One child has shown an excellent response to treatment with subcutaneous GHRH, which is physiologically the most appropriate treatment for this condition...

..7 years. Treatment with hGH resulted in a median increase in height SDS of 0.9. Careful surveillance with timely introduction of GH replacement is required for treatment of GHD following treatment of orbital and parameningeal sarcomas...

..Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established...

..GH insensitivity may be present in children with short stature and an otherwise normal appearance...

..In experienced hands, however, IPSS was feasible in this age group, safe, and strongly predictive of the site of the adenoma, leading to a high rate of successful surgical outcome...

..Adrenals were normal or small on imaging. PRKAR1A gene analysis may be helpful in the assessment of these patients...

..2) or radioiodine (no.=2). In conclusion, disturbance of growth, behavioral difficulties and infrequent spontaneous remission are key features of Graves' disease in early childhood...

..A formal screening programme for this at-risk population of pediatric patients, despite being intensive, can identify VHL lesions during a pre-morbid phase and may thus have a beneficial impact on prognosis in this serious disorder...

..This case shows that the potential value of GH therapy must be evaluated in each patient individually and that an excellent response may occur in a child with a PTPN11-negative genotype...

..These observations strongly support the recommendation to undertake screening of the children of VHL patients...

..CONCLUSION: The LDDST was of diagnostic value by discriminating between CD and other CS aetiologies. In our view the HDDST is redundant in the investigation of paediatric CS...

..To date, this has been difficult to assess in adult GHD of childhood-onset because the relative contributions of low peak bone mass and increased loss of bone in later life could not be distinguished...

..In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth...

..In the standard IGFGT, the IGF-I increase at 36 h was equal to that at 84 h. The low-dose IGFGT, in combination with the standard test, may identify patients with mild GHI...

..To our knowledge, this is the first time in this clinical setting that fertility has been achieved. This case highlights the need for both a functional and histological assessment of such 'tumours' in CAH prior to orchidectomy...

..5 years. Because of actual or incipient virilization, both patients were treated with glucocorticoid replacement 8-12 mg/m(2)/day. This decision is discussed in the context of published guidelines for the management of 21OHD...

..This review article illustrates the embryology of the adrenal with particular emphasis on the relevance of embryology to pathology...

..Appropriate counselling of these patients with regard to their reproductive capabilities is essential...

..CONCLUSION: In our experience, etomidate was effective and safe for short-term control of severe hypercortisolaemia in a severely ill child...

..This article examines the role of GH therapy in short SGA children with particular reference to selection of patients, effectiveness, safety, and its potential metabolic implications...

..None of the 23 children developed hypertrophic cardiomyopathy during GH treatment. Children with any cardiac abnormality at the start of treatment did not show a reduced growth trend when compared with patients with normal hearts...

..GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH secretion and preservation of other anterior pituitary function...

..CONCLUSIONS: Spontaneous GH secretion is elevated in partial GH insensitivity. This investigation could be of diagnostic value in children with short stature...

..These findings suggest that interleukins modulate the IGF-IGFBP system in Caco-2 cells in vitro...

..This paper provides an overview of the major features of these syndromes and suggests protocols for regular screening of children known to be at risk of developing these disorders...

..This paper discusses the role of GH in the attainment of peak bone mass and some of the accumulating evidence that cessation of GH at final height may compromise bone mineral accretion in GH-deficient adolescent patients...

..Observations in boys with delayed puberty and controlled studies in experimental models of intestinal inflammation suggest that testosterone therapy can accelerate puberty...

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..We have investigated a newly developed drug, rhIGF-I/rhIGFBP-3, a 1:1 molar complex of rhIGF-I and rhIGFBP-3...

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..Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals...

..These studies validate the association of the IGF-I gene with birth size and refine the region of association in Swedish short SGA subjects...

..This article describes the study methodology and reviews the association of the exon 3-deleted genotype of the GH receptor with GH responsiveness in GH-treated children born SGA...

..This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS...

..In conclusion, female preponderance of CD in adult patients was not present in childhood. In patients 18 yr of age or younger, there was no difference in the severity of hypercortisolemia or ACTH at diagnosis between males and females...

..The management of paediatric CS patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life...

..CONCLUSIONS: Early increases in IGF-I during treatment of Crohn disease are attributable to the anti-inflammatory effect of the enteral feed rather than nutritional restitution...

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..Histological changes were consistent with JGCT. Immunohistochemical studies revealed positive reactivity to MIC-2, inhibin, melan A, IGF-I and IGFBP-2...

..Recently, mutations in the TPIT gene, a T-box factor selectively expressed in developing corticotroph cells, have been found in cases of early-onset IAD...

..The presence of the pseudoexon results in inclusion of an additional 36-amino acid sequence in a region of the receptor known to be involved in homo-dimerization, which is essential for signal transduction...

..028). However, their risk of developing Crohn's disease was similar to other genotypes when compared with 351 healthy controls (P = 0.7). Thus, the IL-6 -174 genotype mediates growth failure in children with Crohn's disease...

..0 standard deviation score (SDS) if untreated. FH of subjects with high stimulated GH levels has not been studied in detail...

..In 1998, an association between exogenous human GH and retinal pathology in non-diabetic subjects was described...

..To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1beta and IL-6 in inflammatory bowel disease (IBD)...

..Because most diagnostic methods remain crude, however, their modification might be necessary to identify more subtle and yet functionally significant abnormalities of this endocrine axis...

..9 years with height -4.9 SDS, basal GH 344 mIU/ml, IGF-I <12 ng/ml, IGFBP-3 <0.2 mg/ml, and undetectable GHBP. A novel mutation of the GHR, not previously described, was identified at the donor splice site of intron 6...

..We urge paediatric endocrinologists, in collaboration with adult endocrinologists, to perform formal prospective research studies in patients suffering from TBI to clarify these questions...

..We found the use of intraoperative neuronavigation to be an excellent aid in overcoming such anatomic difficulties...

..Complete resolution of the mass was noted after 18 months of hydrocortisone replacement therapy...

..Earlier diagnosis and improved treatment of jejunal disease would be likely to improve final height...

..We investigated 2 sisters from a consanguineous family from Kuwait, with clinical and biochemical features of GHI, in whom no molecular defects in the GHR were identified...

..The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome...