A pilot study proposing an algorithm for pubertal induction in cerebral palsy.

OBJECTIVES: To explore delayed puberty in cerebral palsy (CP) and to test the acceptability of an interventional puberty induction algorithm. METHODS: A two phase cohort study in children and adolescents diagnosed with CP who have delayed puberty. Phase 1: Retrospective review of clinical records and interviews with patients who have been treated with sex-steroids and Phase 2: Prospective interventional trial of pubertal induction with a proposed algorithm of transdermal testosterone (males) or oestrogen (females). Phase 1 examined experiences with sex-steroid treatment. Phase 2 collected data on height adjusted bone mineral density (BMAD), fractures, adverse effects, mobility and quality of life over two years during the induction. RESULTS: Phase 1, treatment was well tolerated in 11/20 treated with sex-steroids; phase 2, using the proposed induction algorithm, 7/10 treated reached Tanner stage 3 by nine months. One participant reached Tanner stage 5 in 24 months. Mean change in BMAD Z-scores was +0.27 % (SD 0.002) in those who could be scanned by dual-energy X-ray absorptiometry (DXA). CONCLUSIONS: Delayed puberty may be diagnosed late. Treatment was beneficial and well tolerated, suggesting all patients with severe pubertal delay or arrest should be considered for sex hormone supplementation.

Global consensus on nutritional rickets: Implications for Australia.

In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.

Disorders of Puberty: Pharmacotherapeutic Strategies for Management.

During puberty, with activation of the hypothalamic pituitary axis that has been quiescent since the neonatal period, linear growth accelerates, secondary sexual characteristics develop, and adult fertility potential and bone mass are achieved, together with psychosocial and emotional maturation.Disordered pubertal onset and progress, either early or late, presents frequently for endocrine care. Where a disorder is found, due either to a central hypothalamic pituitary cause or to primary gonadal failure, pharmacotherapeutic interventions are required to alter the trajectory of disturbed pubertal onset or progress and for maintenance of adolescent and adult sex hormone status. This paper describes pharmacologic interventions used for pubertal disorders but is not intended to address the diagnostic cascade in detail.

Aortic dilatation and dissection in Turner syndrome: what we know, what we are unclear about and what we should do in clinical practice?

Aortic dilatation and aortic dissection are increasingly recognised in patients with Turner syndrome (TS). Risk factors for aortic dissection include aortic dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk of death due to aortic dissection in pregnancy in TS is 2%, which is approximately 100 times higher than the general population, as maternal mortality is extremely low. Ongoing cardiovascular monitoring is recommended, although there remain several unanswered questions in relation to cardiovascular imaging especially the choice of modality for detection of vascular, valvular abnormalities and measurements of aortic dimensions. Due to the relative short stature of patients with TS, aortic dimensions need to be defined by aortic measurements adjusted for body surface area, known as aortic sized index (ASI). The relationship of ASI and other risk factors with aortic dissection is only beginning to be clarified. Clinical management and monitoring of such patients should be delivered by a group of clinicians familiar with the issues unique to TS patients in a multidisciplinary fashion. All clinicians including the non-specialists need to have a low threshold of suspecting aortic dissection in these adolescents and young adults. This up to date review, including a summary of all 122 published cases of TS patients with aortic dissection, aims to provide a summary of recent publications on characteristics of aortic dissection and aortic dilatation in TS to highlight gaps in knowledge and propose possible clinical monitoring pathway of cardiovascular health in children and adults with TS. Cardiovascular assessment and risk counselling is especially crucial during the period of transition of adolescents with TS, although life long monitoring by expert cognizant to the issues specific in TS is essential.

Virginal breast hypertrophy of an 11-year-old girl.

We report a case of an 11-year-old girl with virginal breast hypertrophy; a rare condition characterised by rapid breast enlargement in the peripubertal period. In this paper we highlight complexities of management in this age group.

11beta-hydroxylase deficiency masked by alternative medicines.

A 3.5-year-old Vietnamese boy presented with precocious pseudopuberty, hypertension and a skin rash that was treated with Vietnamese medications for 6 weeks, with resolution. Serum androgen levels were prepubertal, adrenal ultrasound was normal but a large unknown abnormal peak was detected in the urine steroid profile. Cessation of medications disclosed elevation of plasma androgen and 11-deoxycortisol levels. The unidentified urine steroid profile peak disappeared and a tetrahydro-11-deoxycortisol peak was detected. This patient represents a difficult and challenging diagnosis of 11beta-hydroxylase deficiency. Careful evaluation of history and physical finding in the presence of apparent biochemistry discrepancy resulted in a correct diagnosis.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement.

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300,000-500,000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Pamidronate treatment of steroid associated osteonecrosis in young patients treated for acute lymphoblastic leukaemia--two-year outcomes.

AIMS: To assess outcomes of young patients with osteonecrosis (ON) treated with pamidronate in terms of relief of pain, prevention of progress and bony collapse of involved area. PATIENTS AND METHODS: A non-randomised interventional study in six patients with a history of acute lymphoblastic leukaemia (ALL) for which treatment protocols included long-term, high dose use of glucocorticoids. Subsequent development of ON was treated with a bisphosphonate (pamidronate) for 2 years. Mobility and pain control were assessed regularly with MRI and X-ray of affected areas at 0, 12 and 24 months. RESULTS: Reduction in pain was reported in four of six patients in the first year with increased mobility. Two patients who had radiological evidence of joint destruction prior to treatment and when continued on corticosteroids reported no improvement in pain or mobility. In the second year, patients who started treatment in the first few months after diagnosis were stable while patients who had treatment initiated later deteriorated but had less pain than prior to treatment with pamidronate. MRIs of affected areas were completely unchanged over 2 years. X-rays revealed no new bony collapse in four of six patients after 12 months of treatment. However, three of six patients continued to undergo extensive collapse of femoral heads (one at 12 months, two at 24 months) and all these required urgent hip replacement. CONCLUSION: Pamidronate treatment has a palliative effect in control of pain and may delay the natural history of bony collapse in the acute phase of ON, especially in early treated patients, but does not prevent late bone collapse and joint destruction in corticosteroid treated patients with ALL. Larger studies are needed to provide evidence as to whether bisphosphonate is indicated for treatment of ON for patients using corticosteroids.

Postnatal evaluation of vitamin D and bone health in women who were vitamin D-deficient in pregnancy, and in their infants.

OBJECTIVE: To determine the postnatal vitamin D status and bone health of women identified as vitamin D-deficient in pregnancy, and of their infants. DESIGN AND PARTICIPANTS: Retrospective audit conducted between 27 August and 5 November 2003. The study included women delivering between August and October 2002 at the Royal Women's Hospital, Melbourne, who had had a 25-hydroxyvitamin D (25-[OH]D) level < 30 nmol/L in pregnancy, and their infants at age 4-10 months. SETTING: The outpatient clinic at the Royal Children's Hospital, Melbourne. MAIN OUTCOME MEASURES: Maternal and infant serum levels of vitamin D, total alkaline phosphatase (tALP), parathyroid hormone (PTH), calcium and phosphorus; x-ray results in children with clinical or laboratory findings suggestive of rickets. RESULTS: Of 69 mother-infant pairs invited to participate, 47 (68%) attended. All 47 women had 25-(OH)D levels < 50 nmol/L, and 39 (83%) had levels < 30 nmol/L. Vitamin D supplements had been prescribed in pregnancy for 35 women (74%), and 19/35 reported having taken them as prescribed. None had continued to take supplements postnatally, but one had recently started taking them again. Among 45 infants from whom blood samples were successfully obtained, 18 (40%) had 25-(OH)D levels < 50 nmol/L, and 14 (31%) had levels < 30 nmol/L. Twelve of 16 breastfed infants had 25-(OH)D levels < 30 nmol/L, compared with 2/29 fed formula milk (P = 0.001). CONCLUSIONS: Most mothers who had been vitamin D-deficient in pregnancy were also deficient postnatally, indicating that treatment offered, counselling and/or treatment compliance were inadequate. Their infants, especially if breastfed, were at high risk of vitamin D deficiency and increased bone formation. Breastfed infants of mothers at high risk of vitamin D deficiency should receive vitamin D supplements.

Current advances in bone health of disabled children.

PURPOSE OF REVIEW: Bone health is now recognized to contribute to overall lifetime management of children, adolescents, and adults with disabling conditions including physical and intellectual disability and with many chronic disease processes. Such disorders have multiple components, with aspects of care covering a wide number of specialist practices. This review will highlight advances in understanding the nature of bone mass accumulation through childhood and adolescence, the impingement of a spectrum of chronic and disabling diseases and their treatments on bone, and will address current approaches to interpretation of bone mass in the growing skeleton and interventional strategies for improving outcomes for this group. RECENT FINDINGS: Increased skeletal fragility in the disabled child is well recognized. Insights into the contributions of skeletal size and bone strength in males and females have altered interpretation of data, allowing a new focus on determinants of future bone health, particularly with regard to the contributions of growth and puberty. Strategies to address bone health including public and medical education concerning consumption of calcium, appropriate selection of vitamin D preparations, pubertal contribution to phases of growth and possible specialist use of newer drugs, such as bisphosphonates where indicated, are changing the outlook for this large group. SUMMARY: Implications of these changed understandings provide a new focus on maximizing bone mass accumulation by the end of adolescence within the constraints of what is possible to achieve for an individual and for provision of an holistic approach to bone health.