Peter J Simm

Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

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Publications (24)64.69 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: AimThe aim of this paper was to investigate the relationship between circulating 25-hydroxyvitamin D (25(OH)D) and cardio-metabolic risk factors in a large cohort of obese youth attending tertiary paediatric obesity services.Methods We conducted a retrospective cross-sectional study. Data were retrospectively collected from all new consultations of children and adolescents attending obesity outpatient clinics between 2008 and 2011 at the two major paediatric hospitals in Melbourne, Australia. Information collected included demographics, anthropometry, blood pressure, pubertal staging, body composition and fasting serum levels of 25(OH)D, glucose, insulin, cholesterol, triglyceride, high-density lipoprotein, liver function, calcium and phosphate.Results25(OH)D data were available in 229 patients (age 3–18 years; 116 men; mean (standard deviation) body mass index ( BMI) Z-score 2.5 (0.5) ). One hundred four (45%) participants were 25(OH)D deficient (<50 nmol/L). Lower serum 25(OH)D levels were associated with higher BMI Z-score (P-trend = 0.001), total fat mass (P-trend = 0.009), systolic (P-trend = 0.03) and diastolic blood pressures(P-trend = 0.009). In multivariable-adjusted regression analysis, 25(OH)D was significantly lower in those with elevated blood pressure after adjustment for BMI(P-trend = 0.004) or total fat mass (P-trend = 0.01).Conclusion Overweight and obese youth attending specialist obesity services have a high prevalence of vitamin D deficiency. In this population, lower levels of vitamin D were seen in those with greater adiposity, and independent of this, in those who had higher blood pressure.
    No preview · Article · Jul 2015 · Journal of Paediatrics and Child Health
  • [Show abstract] [Hide abstract] ABSTRACT: AimThis study aims to examine the referral practices for the Royal Children's Hospital (RCH) bone density service over the past 13 years and to demonstrate referral patterns and possible limitations to accessing paediatric bone densitometry.Methods All patients attending the RCH Healthy Bones Unit for bone densitometry from 1 July 1999 to 30 June 2012, aged under 18 years of age, were included. Densitometry results were downloaded directly from the Hologic scanner into an Excel document. However, the referring unit and indication for referral were collected manually from either the referral card or the hospital's scanned medical records system.ResultsA total of 5767 bone densitometry scans were performed over the study period on 3004 patients. The majority of referrals were made by the Endocrinology department, followed by Adolescent Medicine, Gastroenterology and Neurology. Relatively few referrals were made by general paediatrics. The most common indication for bone density test overall was eating disorders, followed by steroid use, osteogenesis imperfecta and other collagen disorders and inflammatory bowel disease. The lowest lumbar spine z-scores by indication were for cerebral palsy and other causes of immobility.Conclusions Multiple childhood diseases predispose to low bone density; however, paediatric bone densitometry is still underutilised and not appropriately supported by subsidies.
    No preview · Article · Feb 2015 · Journal of Paediatrics and Child Health
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    [Show abstract] [Hide abstract] ABSTRACT: CASE DESCRIPTION A full-term baby boy underwent an ultrasound scan of the abdomen at 6 weeks of age for the follow-up of an antenatal diagnosis of left-sided hydronephrosis. Although there was no hydronephrosis, the abdominal ultrasound revealed an enlarged liver with multiple hypoechoic lesions measuring up to 25 mm in diameter. He was admitted to the hospital for further evaluation of the hepatic lesions. Examination revealed multiple small external hemangiomas on the scalp and both wrists and axilla. The infant's abdomen was distended with hepatomegaly 6–7 cm below the costal margin. There was no evidence of cardiac failure, an observation that was confirmed by a cardiology consult. His electrolytes, creatinine, urine catecholamine metabolites, α-fetoprotein, and liver enzymes were all within reference intervals, except for an increased γ-glutamyl transferase of 257 IU/L (reference interval, 7–64 IU/L). Thyroid function tests (TFT)7 revealed an increased thyroid-stimulating hormone (TSH) concentration of 37.7 mU/L (age-specific reference interval, 0.30–5.00 mU/L), free thyroxine (fT4) within the reference interval at 17.9 pmol/L (age-specific reference interval, 12.0–30.0 pmol/L), and low free triiodotyronine (fT3) of 3.3 pmol/L (age-specific reference interval, 3.8–6.0 pmol/L) (Beckman DxI, Beckman Coulter). Thyroid peroxidase and thyroglobulin antibodies were negative. The newborn TSH screening test results were within reference intervals. MRI scan of the abdomen showed multiple liver lesions consistent with hemangioendothelioma.
    Full-text · Article · May 2014 · Clinical Chemistry
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    [Show abstract] [Hide abstract] ABSTRACT: Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.
    Full-text · Article · Apr 2014 · Journal of the American Society of Nephrology
  • Kung-Ting Kao · Peter J Simm · Justin Brown
    [Show abstract] [Hide abstract] ABSTRACT: A 9 year old girl presented with seizures, weight gain and early morning behavioural changes. She had been commenced on anticonvulsants and was subsequently diagnosed with hyperinsulinaemic hypoglycaemia. This case demonstrates the importance of blood glucose monitoring in children presenting with new-onset seizures and/or with early morning or fasting behavioural changes, the challenges in localizing the lesion, as well as the difficulties in achieving normoglycaemia prior to, and immediately following, surgery.
    No preview · Article · Apr 2014 · Journal of Paediatrics and Child Health
  • [Show abstract] [Hide abstract] ABSTRACT: Young people with type 1 diabetes mellitus living in rural and regional Australia have previously been shown to have limited access to specialised diabetes services. The Royal Children's Hospital Melbourne has been running diabetes outreach clinics to Western Victoria, Australia, for over 13 years. We aim to evaluate this service by comparing the outcomes of three outreach clinics with our urban diabetes clinic at the Royal Children's Hospital Melbourne. We examine our tertiary, multidisciplinary team-based model of care, where visiting specialist medical staff work alongside local allied health teams. The local teams provide interim care between clinics utilising the same protocols and treatment practices as the tertiary centre. Longitudinal data encapsulating the years 2005-2010, as a cohort study with a control group, are reviewed. A total of 69 rural patients were compared with 1387 metropolitan patients. Metabolic control was comparable, with no difference in mean HbA1c (8.3%/67 mmol/mol for both groups). Treatment options varied slightly at diagnosis, while insulin pump usage was comparable between treatment settings (20.3% rural compared with 27.6% urban, P = 0.19). Of note was that the number of visits per year was higher in the rural group (3.3 per year rural compared with 2.7 urban, P < 0.001). We conclude that the outreach service is able to provide a comparable level of care when the urban model is translated to a rural setting. This model may be further able to be extrapolated to other geographic areas and also other chronic health conditions of childhood.
    No preview · Article · Feb 2014 · Journal of Paediatrics and Child Health
  • No preview · Article · Dec 2013 · Obesity Research & Clinical Practice
  • [Show abstract] [Hide abstract] ABSTRACT: : Aneurysmal bone cysts (ABCs) in the sacrum pose a management challenge as their location usually means that surgical excision is not possible. Strategies such as embolization have been used previously but have the potential for significant side effects. We report the successful use of bisphosphonate treatment (zoledronic acid) in an 8-year-old boy who presented with an ABC that did not respond to embolization. : The patient presented with pain and progressive limp. After radiologic and histologic confirmation of the diagnosis, embolization therapy was trialed, which was unsuccessful. At this point, he had severe pain and extremely limited mobility, requiring the use of a wheelchair. His ability to lie flat or sit erect was limited by the pain. Zoledronic acid therapy was subsequently commenced at 0.04 mg/kg per dose by intravenous infusion, at 4 monthly intervals, for a total of 2 years (7 doses). : The infusions were well tolerated, with rapid reduction in pain and resolution of previously severe immobility, from being bed and chair bound at baseline to normal independent ambulation over several months. This was associated with marked radiologic improvement. We postulate that the effect of treatment is a combination of the anti-inflammatory effect of zoledronic acid and the antiresorptive effect of osteoclast inhibition. : We conclude that bisphosphonates should be considered as possible second-line agents for ABCs. Further, study of a larger cohort would help to establish their efficacy in this setting. : Level IV (case report, no comparator/control arm).
    No preview · Article · Jun 2013 · Journal of pediatric orthopedics
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    [Show abstract] [Hide abstract] ABSTRACT: To determine the incidence of and factors associated with vitamin D deficiency rickets in Australian children. 18-month questionnaire-based prospective observational study, using Australian Paediatric Surveillance Unit (APSU) data. Australian paediatricians and child health workers, January 2006 - July 2007. Children aged ≤ 15 years with vitamin D deficiency rickets (25-hydroxyvitamin D [25OHD] ≤ 50 nmol/L, and elevated alkaline phosphatase levels [> 229 IU/L] and/or radiological rickets). Incidence of vitamin D deficiency rickets. Description of demographics, clinical presentation, identification and further analysis of overrepresented groups, and treatment regimens compared with best-practice guidelines. We identified 398 children with vitamin D deficiency (55% male; median age, 6.3 years [range, 0.2-15 years]). The overall incidence in children ≤ 15 years of age in Australia was 4.9/100 000/year. All had a low 25OHD level (median, 28 nmol/L [range, 5-50 nmol]) and an elevated alkaline phosphatase level (median, 407 IU/L [range, 229-5443 IU/L]), and 48 (12%) were hypocalcaemic. Ninety-five children had wrist x-rays, of whom 67 (71%) had rachitic changes. Most (98%) had dark or intermediate skin colour and 18% of girls were partially or completely veiled. Most children were born in Africa (252; 63%) and 75% of children were refugees. Duration of exclusive breastfeeding was inversely related to serum vitamin D levels in children < 3 years of age. Empirical vitamin D treatment was given to 4% of children before diagnosis. Vitamin D deficiency rickets is a significant problem in Australia among known high-risk groups. Public health campaigns to prevent, identify and tre@vitamin D deficiency, especially in high-risk groups, are essential.
    Full-text · Article · Apr 2012 · The Medical journal of Australia
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    [Show abstract] [Hide abstract] ABSTRACT: There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated with 3 monthly zoledronic acid for 2 years (annualised dose 0.1mg/kg/year). There was a significant improvement in lumbar spine (by 1.88 SD±1.24 over first 12 months, p<0.001) and total bone mineral density as assessed by dual energy absorptiometry (DXA) scans, with a similar increase in bone mineral content for lean tissue mass (mean increase 1.34 SD in first 12 months, p<0.001). Bone turnover was reduced with a suppression of both osteocalcin and alkaline phosphatase in the first 12 months of treatment. Skeletal architecture was improved, with increased second metacarpal cortical thickness from 2.44mm to 2.72mm (p<0.001) and improved vertebral morphometry, with 7 patients who had vertebral wedging at baseline showing improved anterior (p=0.017) and middle (p=0.001) vertebral height ratios. Aside from well reported transient side effects with the first dose, there were no adverse effects reported. No adverse effects on anthropometric parameters were seen over the course of the study. Despite all patients having sustained fragility fractures prior to treatment, no fractures were reported during the study period. Further evidence is required to confirm efficacy, with long term follow up required to assess the impact of treatment on fracture risk.
    Full-text · Article · Jul 2011 · Bone
  • Peter J Simm · Vincenzo C Russo · George A Werther
    [Show abstract] [Hide abstract] ABSTRACT: While oestrogen is recognized to play a key role in regulating growth, particularly in relation to epiphyseal fusion, the mechanisms that mediate its effects are still unclear. We utilized an in vitro model of chondrogenesis, the RCJ3.1C5.18 cell line, to explore the effect of oestrogen on this process. We demonstrated the presence of oestrogen receptors (ER) α and β in these cells, with increased abundance of both receptor sub-types evident as the cells differentiated. ERα localized to the nucleus, suggesting it was signalling by genomic pathways, while ERβ was seen predominantly in the cytoplasm, suggesting it may be utilizing non-genomic signalling. While exogenous oestrogen had no effect on proliferation or differentiation, we found some evidence for the endogenous production of oestrogen (intracrinology), as suggested by the expression of aromatase in these cells. Selective ERα blockade with methyl piperidinopyrazole (MPP) led to a significant reduction in both proliferation and differentiation, while ERβ blockade with R,R tetrahydrochrysene (THC) led to an increase in these parameters. This is in keeping with results from mouse knockout models suggesting that unopposed ERβ signalling leads to an inhibition of skeletal growth. Our results are further evidence for the importance of differential ER signalling in regulating chondrogenesis. Future studies examining in vivo effects of these agents are required to extrapolate these findings to a mammalian model.
    No preview · Article · May 2011 · Endocrine
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    [Show abstract] [Hide abstract] ABSTRACT: Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved.
    Full-text · Article · Oct 2010 · Journal of Endocrinology
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    P J Simm · J Briody · M McQuade · C F Munns
    [Show abstract] [Hide abstract] ABSTRACT: Complex regional pain syndrome (CRPS) is a disorder that can cause significant functional morbidity. While it usually presents in adulthood, it has also been reported in children. Multiple treatment modalities have been reported with mixed success. Bisphosphonate therapy has been shown to be effective in adult patients, but there are limited data in children. We report the successful use of intravenous pamidronate therapy in diminishing pain, improving function, and restoring bone mass in an 11-year-old girl with CRPS of her left lower limb following a tibial fracture. Previous treatment with intense physiotherapy and regional sympathetic blockade had not improved her symptoms. Pain improved within weeks of the first pamidronate infusion, with subsequent improvement in function. The benefit in pain reduction and function was sustained during the 2-year treatment regime. Improvement in bone mass and density was demonstrated by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerised tomography (pQCT). pQCT scans showed marked improvement in bone size and geometry and muscle bulk on the affected side. No adverse affects were reported. We conclude that intravenous pamidronate was associated with reduced pain, a return of function, and recovery of bone and muscle parameters in a child with CRPS. Before definitive conclusions can be drawn, a randomised controlled trial similar to those undertaken in adults previously is required to fully validate this approach.
    Full-text · Article · Dec 2009 · Bone
  • [Show abstract] [Hide abstract] ABSTRACT: Recent research has demonstrated that mutations of the hepatocyte nuclear factor 4-alpha (HNF4A) gene are associated with neonatal hyperinsulinaemic hypoglycaemia. Mutations of this gene also cause one of the subtypes of monogenic diabetes, a form of diabetes formerly known as maturity-onset diabetes of the young. This article describes a family discovered to have a novel frame-shift mutation of the HNF4A gene in the setting of early-onset maternal diabetes and severe neonatal hyperinsulinaemic hypoglycaemia. The implications of a diagnosis of HNF4A gene mutation for obstetric and paediatric practice are discussed.
    No preview · Article · Jul 2009 · Australian and New Zealand Journal of Obstetrics and Gynaecology
  • P. J. Simm · M. R. Zacharin
    No preview · Article · May 2009 · Bone
  • Article: Reply.
    Peter J Simm · Roger C Allen · Margaret R Zacharin
    No preview · Article · Feb 2009 · The Journal of pediatrics
  • P J Simm · A Bajpai · V C Russo · GA Werther
    [Show abstract] [Hide abstract] ABSTRACT: Estrogen plays a key role in the regulation of growth in both genders, via its stimulation of the pubertal growth spurt and mediation of epiphyseal fusion. Mouse knockout models suggest a differential effect of oestrogen receptor (ER) alpha and beta on the growth plate, with ER beta possibly being more important in regulating epiphyseal fusion. Epiphyseal fusion may also depend on growth plate senescence, which is regulated by oestrogen. While molecular mechanisms for oestrogen's actions remain unclear, local production of oestrogen may be important for growth. Aromatase inhibitors appear to be effective in improving final height outcome in short stature, however long term safety data is lacking particularly in regards to reproductive function. Future studies are required to further understand the mechanisms by which ER alpha and ER beta affect growth plate function, while longer term studies of aromatase inhibitor usage, preferably utilising animal models, are required to verify the safety of these compounds.
    No preview · Article · Oct 2008 · Pediatric endocrinology reviews: PER
  • Peter J Simm · Roger C Allen · Margaret R Zacharin
    [Show abstract] [Hide abstract] ABSTRACT: To test the safety and efficacy of biphosphonates in chronic recurrent multifocal osteomyelitis (CRMO). Five patients with CRMO, all of whom had ongoing pain and loss of function despite conventional treatment with non-steroidal anti-inflammatory agents, were treated with pamidronate (1 mg/kg/dose with a dosing frequency of 2 to 4 monthly for a total treatment duration of 12 to 42 months). Pain decreased after the first infusion for 4 of 5 patients, with symptomatic improvement maintained with time. Significant improvement was seen in radiological lesions for these 4 patients. Bisphosphonates appear to be a useful and safe adjunctive treatment in CRMO when simple therapies such as anti-inflammatory agents fail to control symptoms or cases in which lesion expansion continues.
    No preview · Article · May 2008 · The Journal of pediatrics
  • Peter J Simm · Margaret R Zacharin
    [Show abstract] [Hide abstract] ABSTRACT: 11 beta-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. There have been no previous reports in the literature of a successful pregnancy in a severely affected female. We report the first successful pregnancy resulting in a live birth for a female with 11 beta-hydroxylase deficiency and outline management issues from preconception to successful birth. We also report 2 novel mutations in the CYP11B1 gene leading to 11 beta-hydroxylase deficiency.
    No preview · Article · Feb 2007 · Hormone Research
  • P J Simm · M R Zacharin
    [Show abstract] [Hide abstract] ABSTRACT: To describe psychosocial morbidity in a cohort of young males with hypogonadism due to Klinefelter syndrome, to document the effect of androgen replacement on behaviour, to underline issues confronting clinicians involved in treatment of this condition and to demonstrate a need for a structured program for prospective intervention for this group. We also compare this group to young men with hypogonadotrophic hypogonadism. A retrospective audit of patients with Klinefelter and Kallmann syndromes, presenting for medical assessment from 1994-2004. Postpubertal males with Klinefelter syndrome (n = 32) and Kallmann syndrome (n = 19) were audited by chart review for psychosocial comorbidities, pubertal management, and the need for exogenous testosterone. Seventeen of 32 postpubertal patients with Klinefelter syndrome required testosterone therapy while 11 were documented to have serum testosterone in the normal adult range. All patients with Kallmann syndrome required long term testosterone treatment. Significant psychosocial and behavioural problems were present in 22/32 of patients with Klinefelter syndrome, including seven who were testosterone replete, with an identifiable pattern of disorder, including marked lack of insight, poor judgement and impaired ability to learn from adverse experience. Use of long term replacement testosterone treatment reduced episodes of behavioural indiscretion. Of those patients with Kallmann syndrome, 5/19 reported mild depressive symptoms only, all resolving with testosterone replacement. Inadequately treated hypogonadism in Klinefelter syndrome increases recognized psychosocial morbidity. There is a need for prospectively planned and timed support for young men with Klinefelter syndrome, to ameliorate current poor psychosocial outcomes.
    No preview · Article · May 2006 · Journal of pediatric endocrinology & metabolism: JPEM