Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

CASE A 4-week-old boy presented with a 24-h history of decreased energy, oral intake and urinary output, 3 days of nonbilious emesis and pale stools. Born term (weight 3655 g, pregnancy and delivery uneventful), a hypoglycaemic episode at a few hours of life, was corrected with intravenous glucose. Phototherapy was required a few days later for jaundice. Newborn screening and family history were noncontributory. Investigations on admission revealed a Klebsiella pneumoniae urinary tract infection, blood and CSF glucose of 0.4 and 0.2 mmol/L, respectively, and a total and direct bilirubin of 142.8 and 68.9 lmol/L, respectively. He received intravenous dextrose and was transferred to our centre. Physical examination revealed a pale, jaundiced boy (weight 3.590 kg, 3rd–15th percentile; length 51 cm, 3rd percentile; head circumference 37 cm, 15th–50th percentile), with normal vital signs, micropenis and undescended testes. Initial investigations (on 10% IV dextrose and formula feeds) confirmed direct hyperbilirubinaemia but were otherwise unremarkable. Abdominal ultrasound was normal, hepatobiliary scintigraphy showed a patent biliary tree, but delayed excretion time. Further investigations, including a cranial MRI (Fig. 1), revealed the diagnosis.

Acta PaediatricaVolume 102, Issue 11 p. 1104-1105 Quest for the Diagnosis A 4-week-old boy with emesis and pale stools (Discussion and Diagnosis) E Kelland, E Kelland Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, CanadaSearch for more papers by this authorC Clarson, C Clarson Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, Canada Lawson Health Research Institute, London Health Sciences Centre, London, ON, CanadaSearch for more papers by this authorDE Bock, Corresponding Author DE Bock [email protected] Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, Canada Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada Correspondence Dirk E. Bock, Assistant Professor of Pediatrics, Children's Hospital, London Health Science Centre, University of Western Ontario, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. Tel: +1 519 685 8500, ext. 56075 | Fax: +1 519 685 8156 | Email: [email protected]Search for more papers by this author E Kelland, E Kelland Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, CanadaSearch for more papers by this authorC Clarson, C Clarson Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, Canada Lawson Health Research Institute, London Health Sciences Centre, London, ON, CanadaSearch for more papers by this authorDE Bock, Corresponding Author DE Bock [email protected] Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, ON, Canada Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada Correspondence Dirk E. Bock, Assistant Professor of Pediatrics, Children's Hospital, London Health Science Centre, University of Western Ontario, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. Tel: +1 519 685 8500, ext. 56075 | Fax: +1 519 685 8156 | Email: [email protected]Search for more papers by this author First published: 03 October 2013 https://doi.org/10.1111/apa.12381Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Alatzoglou KS, Dattani MT. Genetic forms of hypopituitarism and their manifestation in the neonatal period. Early Hum Dev 2009; 85: 705–12. 2Castinett F, Reynaud R, Saveanu A, Quentien MH, Albarel F, Barlier A, et al. Clinical and genetic aspects of combined pituitary hormone deficiencies. Ann Endocrinol (Paris) 2008; 69: 7–17. 3Ascoli P, Cavagnini F. Hypopituitarism. Pituitary 2006; 9: 335–42. 4Cooper MS, Stewart PM. Diagnosis and treatment of ACTH deficiency. Rev Endocr Metab Disord 2005; 6: 47–54. 5Binder G, Martin DD, Kanther I, Schwarze CP, Ranke MB. The course of neonatal cholestasis in congenital combined pituitary hormone deficiency. J Pediatr Endocrinol Metab 2007; 20: 695–701. 6Mehta A, Dattani MT. Developmental disorders of the hypothalamus and pituitary gland associated with congenital hypopituitarism. Best Pract Res Clin Endocrinol Metab 2008; 22: 191–206. 7Jagtap VS, Acharya SV, Sarathi V, Lila AR, Budyal SR, Kasaliwal R, et al. Ectopic posterior pituitary and stalk abnormality predicts severity and coexisting hormone deficiencies in patients with congenital growth hormone deficiency. Pituitary 2012; 15: 243–50. 8Turcu AF, Erickson BJ, Lin E, Guadalix S, Schwarz K, Scheithauer BW, et al. Pituitary stalk lesions: The mayo clinic experience. J Clin Endocrinol Metab 2013; 98: 1812–18. 9Van Aken MO, Lamberts SWJ. Diagnosis and treatment of hypopituitarism: an update. Pituitary 2005; 8: 183–91. 10Richmond EJ, Rogol AD. Growth hormone deficiency in children. Pituitary 2008; 11: 115–20. Volume102, Issue11November 2013Pages 1104-1105 ReferencesRelatedInformation

Summary Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). Introduction Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. Methods Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. Results Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. Conclusions Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

DMD is the most common childhood neuromuscular disorder causing loss of ambulation in early life. Steroids are currently used to improve muscle strength and prolong ambulation although the effect on bone health in this group of children is still unclear. The aim of this study was to compare bone strength in healthy children to bone strength in children with DMD and investigate the interaction between high dose oral steroids and diminished muscle function. Forty-seven children were studied, 18 healthy boys (mean age 9.0±1.5 years) and 29 boys with DMD (mean age 9.1±2.5 years). Of the 29 boys with DMD 9 were ambulant and had not started on steroids, 14 were ambulant and had taken steroids for at least 12 months (mean 25.4 ±11.0 months) and 6 were no longer ambulant and had taken steroids for between 14 and 45 months (mean 37.2 ±11.7 months). Peripheral quantitative computed tomography was used to measure bone geometry, density and strength and muscle mass of the non-dominant tibia. Measurements were made at the distal metaphysis and mid diaphysis sites taken as 4 & 66% of the tibial length, respectively. Data were adjusted for age & height and differences between the four groups evaluated. In general, at the distal metaphysis, healthy boys had larger bones (21.3%, p<0.001) which were more dense (18.4%, p<0.001) than the boys with DMD. The greatest differences were observed between healthy and non-ambulant DMD boys, where bone area and bone density were reduced by 41.6% and 32.0%, respectively. No significant differences were observed between ambulant steroid and non steroid DMD boys, for these parameters. At the mid diaphysis, cross-sectional tibial area, cortical area, cortical bone mass and the stress-strain index (a surrogate measure for bone strength) were all reduced in DMD boys by 40.0%, 29.2%, 22.4% & 31.5%, respectively (p<0.001). Once again this effect was most striking in the boys who had lost ambulation, with no differences detected between ambulant steroid and non steroid DMD boys. In contrast, DMD boys had significantly greater muscle mass (48.4%, p<0.001) but with greatly diminished function. In addition, there were no significant differences in cortical density. In summary, this data suggests that ambulation and hence muscle function & gravitational load has the greatest effect on bone strength and density in boys with DMD. In contrast, whilst they remain ambulant the effect of the relatively high dose steroids appears to be negligible. This information is likely to be useful when considering potential interventions for maximising bone strength as these boys go through puberty in to young adulthood.

Society of Critical Care Medicine; 28th Educational and Scientific Symposium; San Francisco, California, USA; January 23-27, 1999: Poster Presentations: Poster Hall

Objective. Familial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premature atherosclerosis. The recommended pediatric therapy consists of dietary intervention and, when necessary, treatment with bile acid-binding resins. However, compliance has been poor in many children. Therefore, our objectives were to determine the efficacy, safety, and tolerance of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitor, in the control of severe FH in a male pediatric population and to evaluate the dose-response relationship.Methods. Sixty-nine male patients with FH 12.9 +/- 2.4 years of age (mean +/- SD) participated in this multicenter, randomized, double-blind trial. After a 4-week placebo period, the patients were allocated to four treatment groups (lovastatin 10, 20, 30, or 40 mg/d) for 8 weeks. Plasma lipid and apolipoprotein (Ape) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monitored periodically throughout the study.Results. All lovastatin doses reduced total cholesterol (-17% to -29%), low-density lipoprotein cholesterol (-21% to -36%), and ApoB (-19% to -28%) concentrations. A dose-response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We observed a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated by all patients. No serious clinical adverse experience was reported. Lovastatin increased aspartate aminotransferase concentrations, but there was no evidence of a dose-response relationship, and no value exceeded two times the upper limit of normal. No significant change in alanine aminotransferase was observed. Three patients had marked (more than three times the upper limit of normal) asymptomatic elevations in their creatine kinase values, which returned spontaneously to normal, and no action was required regarding the drug.Conclusions. Lovastatin is an effective therapy for severe FH in children and adolescents. It was well tolerated, and the occurrence of adverse experiences of clinical significance was very low. Long-term pediatric studies are indicated.

The objective of this study was to determine the risk of death and potential for prevention of mortality in a large population of children with growth hormone deficiency (GHD). The Canadian GH Advisory Committee registry was initiated in 1967 to include all persons in Canada treated with pituitary-derived GH (1967-1985). Since 1985, the registry has been maintained for continuous surveillance of those treated with biosynthetic GH. Thirty-seven children have died out of a total of 1366 children treated for GHD in the 25 years up to December 31, 1992. Individual cases were reviewed for circumstances before death and autopsy information. The likelihood of individual deaths being caused by potentially preventable endocrine causes was graded on a scale of 1-5. Survival curves were analyzed for the children with idiopathic GHD and craniopharyngioma. Age- and sex-specific mortality rates for children with idiopathic GHD were compared with those of the general population. The overall crude mortality rate was 2.7%. The most frequent cause of mortality was tumor recurrence (11/37). A surprisingly high proportion of deaths (9/37) were caused by the preventable endocrine complications of adrenal crisis and hypoglycemia. Children with idiopathic GHD receiving GH therapy had similar age- and sex-specific mortality rates compared with general population rates, except in a high-risk subgroup of males diagnosed with GHD before 2 yr of age. The highest mortality occurred in children with GHD secondary to craniopharyngioma. We concluded that preventable sudden deaths caused by adrenal crisis continue to occur in children with hypopituitarism. A high level of vigilance must be maintained in this population.

OBJECTIVEFamilial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premature atherosclerosis. The recommended pediatric therapy consists of dietary intervention and, when necessary, treatment with bile acid-binding resins. However, compliance has been poor in many children. Therefore, our objectives were to determine the efficacy, safety, and tolerance of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitor, in the control of severe FH in a male pediatric population and to evaluate the dose-response relationship.METHODSSixty-nine male patients with FH 12.9 +/- 2.4 years of age (mean +/- SD) participated in this multicenter, randomized, double-blind trial. After a 4-week placebo period, the patients were allocated to four treatment groups (lovastatin 10, 20, 30, 40 mg/d) for 8 weeks. Plasma lipid and apolipoprotein (Apo) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monitored periodically throughout the study.RESULTSAll lovastatin doses reduced total cholesterol (-17% to -29%), low density lipoprotein cholesterol (-21% to -36%), and ApoB (-19% to -28%) concentrations. A dose-response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We observed a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated by all patients. No serious clinical adverse experience was reported. Lovastatin increased aspartate aminotransferase concentrations, but there was no evidence of a dose-response relationship, and no value exceeded two times the upper limit of normal. No significant change in alanine aminotransferase was observed. Three patients had marked (more than three times the upper limit of normal) asymptomatic elevations in their creatine kinase values, which returned spontaneously to normal, and no action was required regarding the drug.

Acquired hypothyroidism is more common in children with Down syndrome than in other children. In children without Down syndrome, acquired hypothyroidism is rare before age 3 years and is not reported to occur frequently until adolescence.1Previous reports of hypothyroidism in children with Down syndrome have described onset at a similar age. Postneonatal-onset hypothyroidism in the very young children with Down syndrome described herein has not previously been reported, to our knowledge. At the Child and Parent Resource Institute in London, Ontario, we have a multidisciplinary outpatient developmental program for children with Down syndrome. At the time of this writing, we had approximately 120 children aged between 6 weeks and 17 years in the program. Patient Reports.Patient1. This 6½-month-old female infant was born at 37 weeks' gestation to a 39-year-old mother who had a distant family history of thyroid disease. The mother and father were third cousins.

The placenta from 30 women with diabetes mellitus were examined and weighed at delivery. Nineteen of these were from women with overt and eleven from women with gestational diabetes. Eleven placentae from normal pregnancies served as controls. There was no difference between the mean ± s.d. placental weight for the diabetic group and the control group (609 ± 148 versus 591 ± 93 g, NS). The mean placental weight ratios for the diabetic group and the control group were also similar (0.98 ± 0.23 versus 0.89 ± 0.15, NS). Moreover, there was no difference between the weights and weight ratios of placentae from women with overt (622 ± 173 g, 1.02 ± 0.27) and those with gestational diabetes (586 ± 90 g, versus 0.90 f 0.13). Placental weights correlated with birthweights (r = 0.70, P < 0.01) and with skinfold thickness measurements of the infants (r = 0.40, P < 0.05), but neither with gestational ages (r = 0.15, NS) nor with maternal glycosylated haemoglobin levels in the third trimester (r = 0.24, NS). Among the women with overt diabetes, placental weights were greater in those in White's class B and C than those in class D and R (689 ± 143 versus 530 ± 177 g; P < 0.05). In general, placentae from well controlled diabetic patients were not heavier than those from normal pregnant women, although there was an increase in placental weight in White's class B and C, as compared with those in class D and R.

We measured serum C-peptide, glucose, pH, islet antibodies and insulin antibody binding at diagnosis in 84 children with Type 1 (insulin-dependent) diabetes. In a subgroup of 33 children, residual insulin secretion (basal and peak C-peptide response to Sustacal), insulin antibody binding and HbA1c were measured at 10 days, 1, 3, 6 and 12 months. At presentation C-peptide correlated positively with age at onset and negatively with the blood glucose concentration. Median C-peptide concentration at diagnosis was low, rose significantly (p<0.05) at 10 days, reached a maximum at 1–3 months and declined gradually to 1 year. C-peptide concentration both at diagnosis and at 10 days correlated with that at 3 and 6 months. Of the factors investigated, only age (p<0.005) and sex (higher in females, p<0.01) were found to have a significant influence on basal/peak C-peptide levels throughout the first year. In particular there was no relationship between C-peptide, HbA1c and insulin dose during this period. A peak C-peptide response at 3–6 months>/<0.32 nmol/l was used to divide the group into two: 16 had a peak response <0.32 nmol/l (low secretors) while in 17, the peak C-peptide was >0.32 nmol/l (high secretors). While the low secretors had significantly (p<0.05) lower C-peptide levels during the first year, there were no differences between low and high secretors in HbA1c or insulin dose. These data suggest that there are two patterns of residual insulin secretion during the first 12 months after diagnosis of Type 1 diabetes. One pattern shows good amplitude and duration of residual insulin secretion, while both these features are significantly (p<0.05) reduced in the other. The C-peptide concentration both at diagnosis and at 10 days, as well as age at onset and sex are important predictors of the pattern to be followed. Our data suggest further that the magnitude of residual insulin secretion does not play a decisive role in metabolic control during this period.

Reproducibility of C-peptide secretion was assessed in 20 children (group 1) by their responses to two Sustacal- (a mixed liquid meal) stimulation tests performed 7–14 days apart. For the 12 C-peptide-positive children (basal C-peptide ≥0.03 pmol/ml) there were no differences in the basal or stimulated values between tests 1 and 2. The effect of exogenous insulin on C-peptide secretion was assessed in 20 other children (group 2) by their responses to two Sustacal tests, one test without and one with soluble insulin (0.25 U/kg) injected subcutaneously before testing. Eleven children were C-peptide positive and had no differences in C-peptide response between tests 1 and 2. The results from test 1 in groups 1 and 2 were combined with those from 44 others undergoing a single Sustacal test (group 3, N = 84). There was a close correlation between basal and peak C-peptide concentrations in the 44 C-peptide-positive children (r = .88, P < .001). Peak C-peptide concentrations correlated inversely with HbA1 (r = −.29, P < .01), insulin dose in units per kilogram (r = −.40, P < .001), and duration of diabetes (r = .33, P < .001) and positively with age at onset of diabetes (r = .34, P < .001). The C-peptide-positive children had reduced glucose response to Sustacal, lower HbA1 concentration, lower insulin requirement, later age of onset, and shorter duration of diabetes than children who were C-peptide negative.

Application of continuous distending pressure at birth (very early CDP) should stabilize the immature airways and reduce the severity of respiratory distress syndrome (RDS) in preterm infants. Eighty-two preterm infants of less than 32 weeks gestation were randomly assigned at birth to early treatment group (TG), in which CDP of 6 cm water pressure was applied at birth by the nasopharyngeal route (NP-CDP), or to control group (CG), in which CDP was applied when indicated for established criteria (pO2 less than 50 mmHg in FiO2 greater than 0.5). Characteristics of the infants in the two groups were comparable. No statistically significant difference between the two groups was found in the incidence of RDS. The course of RDS, and oxygen and ventilatory requirements also did not appear to be changed. In blood gas parameters of most of the time frames, no significant difference was found between the two groups when the results were analyzed according to the assigned group. When the results were analyzed separately for the infants who developed RDS, infants in TG appear to have fared worse from the therapy in terms of oxygenation, as indicated by significantly higher FiO2 (P less than 0.01) and lower a/A (P less than 0.01) values on the third day of the course of RDS, as compared to infants in CG. The incidence of complications was comparable in the two groups. Four infants from TG (9.3%) and one from CG (2.6%) died (P = NS). We conclude that VECDP by nasopharyngeal route does not reduce the incidence of RDS and does not appear to improve the outcome and may worsen the severity of RDS when compared to application of CDP for established criteria.

Environmental "triggers" (including viruses, toxins and dietary factors) have been implicated in the pathogenesis of insulin-dependent diabetes mellitus. Data have suggested a possible role for cow's milk protein (CMP) as a trigger of diabetes. To study this further, 86 BB rats were divided into 2 groups during the weaning period (days 13-25): Group A received rat chow without CMP; Group B, rat chow with 1% CMP added. Each group was subdivided afterwards into 2: Groups A1 and B1 received chow without CMP; Groups A2 and B2, chow with CMP. Animals weaned with chow containing CMP (B1 and B2) had a higher incidence of diabetes (66%) than those weaned without (A1 and A2; 29%, p less than 0.001). The incidence in both B1 and B2 was significantly greater than in either A1 or A2 (p less than 0.05). The highest incidence of diabetes occurred in male rats weaned on rat chow with CMP (90%), the incidence being significantly higher than female rats weaned with (43%) or without CMP (18%) and males weaned without CMP (39%). Thus, it appears that (a) the presence of cow's milk protein in the diet increases the incidence of diabetes in the BB rat; (b) the critical time for exposure to CMP appears to be the weaning period; and (c) male rats appear to be more susceptible to the development of diabetes than female rats, when exposed to this trigger. This supports the hypothesis that dietary triggers may play an important role in the expression of diabetes in the susceptible host and that its prevalent action occurs early in life.

We studied residual beta-cell function in 84 children with IDDM to assess (1) relationship between basal and stimulated C-peptide concentrations; (2) reproducibility of testing (Group 1, n = 20); (3) the effect of exogenous insulin on test interpretation (Group II, n = 20); and (4) impact on metabolic control. Sustacal (a mixed liquid meal) was utilized as the test stimulus. In C-peptide positive subjects (n = 44) there was a strong correlation between basal and peak C-peptide concentrations (r = 0.88, p less than 0.001). In Group 1 subjects, Sustacal proved to be a highly reproducible test stimulus producing identical results on two tests 7-14 days apart. The results of the tests were not affected by the administration of subcutaneous regular insulin prior to the second test in Group II. Peak C-peptide correlated inversely with HbA1, insulin dose, and disease duration (r = -0.29, -0.40, and -0.33 respectively, p less than 0.05) and positively with age (r = 0.34, p less than 0.05). We conclude that Sustacal is a highly reproducible stimulus to residual beta-cell function in IDDM and is not affected by exogenous insulin. This residual insulin secretion has a small but significant effect on glycemic control.