Burosumab treatment for fibrous dysplasia.

BACKGROUND: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare mosaic disorder of Gαs activation. Fibroblast Growth Factor 23 (FGF23)-mediated hypophosphatemia is a feature of FD/MAS that has been associated with poor skeletal outcomes. Standard therapy includes oral phosphorus and vitamin D analogs; however, treatment is limited by potential adverse renal and gastrointestinal effects. Burosumab is a monoclonal antibody to FGF23 approved to treat patients with X-linked hypophosphatemia and tumor-induced osteomalacia. There is currently no safety or efficacy data to support burosumab use in patients with FD/MAS. CASE DESCRIPTION: A 7-year-old boy with severe FD/MAS presented with persistent hypophosphatemia and skeletal complications despite conventional treatment with oral phosphate and calcitriol. He was started on burosumab and achieved sustained normalization of serum phosphorus and marked improvement in alkaline phosphatase levels. This was accompanied by an encouraging clinical response, including decreased bone pain, improved muscle strength, and improved ambulation. No adverse effects of burosumab therapy were observed. CONCLUSIONS: This is the first reported case of burosumab treatment in a patient with FD/MAS. The encouraging biochemical and clinical response in this patient highlights the need for future studies to explore the safety and efficacy of burosumab in the FD/MAS pediatric population.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury.

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Differences in the management of adolescents with polycystic ovary syndrome across pediatric specialties.

STUDY OBJECTIVE: Evaluate for differences in the management of adolescents with polycystic ovarian syndrome (PCOS) across 3 pediatric specialties. DESIGN: Retrospective review of medical records. SETTING: Academic children's hospital. PARTICIPANTS: 181 adolescents seen between July 2008 and June 2010 by providers in Pediatric Endocrinology (PEndo), Adolescent Medicine (AMed), or Pediatric and Adolescent Gynecology (PGyn) identified via billing data (ICD-9 code for PCOS, 256.4). INTERVENTIONS: None. MAIN OUTCOME MEASURES: (1) Percentage of adolescents with a billing diagnosis of PCOS who met diagnostic criteria; (2) Percentage of individuals screened for comorbidities and differences across specialties; (3) Differences in treatment recommendations across specialties; (4) Factors associated with recommendation for metformin and hormonal contraceptives. RESULTS: Thirteen percent of PEndo patients did not meet diagnostic criteria for PCOS; 20% of AMed and PGyn patients did not meet criteria. There were significant differences in rates of screening for obesity, insulin resistance, and Type 2 diabetes. There were significant differences in treatment recommendations for lifestyle changes, metformin, and anti-androgen therapy across specialties. Specialty and obesity were significant predictors of metformin recommendation; specifically PEndo predicted metformin recommendation. PGyn and AMed specialties predicted hormonal contraceptive recommendation. CONCLUSIONS: The variability observed among specialties may be due to differences in training, accounting for a range of comfort with aspects of PCOS. Formulation of consensus guidelines for diagnosis and management of PCOS are needed, along with broad educational efforts. By correctly diagnosing, screening for comorbidities, and managing PCOS appropriately during adolescence, providers may reduce the risk for long-term consequences.

Endocrine changes after pediatric traumatic brain injury.

Traumatic brain injury (TBI) is a very common occurrence in childhood, and can lead to devastating long term consequences. Recent research has focused on the potential endocrine consequences of TBI in adults. The research in children is less robust. This paper reviews current literature regarding TBI and possible hypothalamic and pituitary deficiencies in childhood. Acute endocrine changes are commonly found after TBI in pediatric patients, which can include changes in hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release. In the long term, both temporary and permanent alterations in pituitary function have been found. About 30% of children have hypopituitarism up to 5 years after injury. Growth hormone deficiency and disturbances in puberty are the most common, but children can also experience ACTH deficiency, diabetes insipidus, central hypothyroidism, and elevated prolactin. Every hormonal axis can be affected after TBI in children, although growth hormone deficiency and alterations in puberty are the most common. Because transient and permanent hypopituitarism is common after TBI, survivors should be screened serially for possible endocrine disturbances. These children should undergo routine surveillance at least 1 year after injury to ensure early detection of deficiencies in hormonal production in order to permit normal growth and development.