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.

Randomized Controlled Trial Evaluating the Use of Zoledronic Acid in Duchenne Muscular Dystrophy.

CONTEXT: Patients with glucocorticoid-dependent Duchenne muscular dystrophy (DMD) have increased fracture risk and reduced bone mineral density (BMD), often precipitating mobility loss. OBJECTIVE: To investigate use of zoledronic acid (ZA) in DMD in improving BMD. METHODS: Two arm, parallel, randomized controlled trial, set in pediatric hospitals across Australia and New Zealand. Sixty-two (31 per arm) boys with glucocorticoid-dependent DMD between 6 and 16 years were included. Five ZA infusions (0.025 mg/kg at months 0, and 3, and 0.05 mg/kg at months 6, 12, and 18), plus calcium and vitamin D, were compared with calcium and vitamin D alone. The main outcome measures were change in lumbar spine (LS) BMD raw and Z-score by dual energy absorptiometry x-ray (DXA) at 12 and 24 months, secondary outcomes assessing mobility, fracture incidence, bone turnover, peripheral quantitative computerized (pQCT) and pain scores. RESULTS: At 12 and 24 months, mean difference in changes of LS BMD Z-score from baseline was 1.2 SD (95% CI 0.9-1.5), higher by 19.3% (14.6-24.0) and 1.4 SD (0.9-1.9), higher by 26.0% (17.4-34.5) in ZA than control arms respectively (both P < .001). Five controls developed Genant 3 vertebral fractures, 0 in the ZA arm. Mobility, pain, and bone turnover markers were similar between arms at 12 and 24 months. Trabecular BMC and vBMD pQCT at radius and tibia were greater at 12 months in the ZA cohort than control; the evidence for this difference remained at 24 months for radius but not tibia. CONCLUSION: ZA improved BMD in glucocorticoid-dependent DMD boys. Although the small cohort precluded demonstrable fracture benefit, improved BMD might reduce incident vertebral fracture.

Hormone modeling in preterm neonates: establishment of pituitary and steroid hormone reference intervals.

CONTEXT: Reports suggest significant differences in serum levels of hormones in extremely preterm compared with late preterm and full-term infants. OBJECTIVES: The purpose of this study was to develop reference intervals (RIs) for 3 pituitary hormones and 5 steroid hormones in serum of preterm infants. DESIGN: Blood samples were collected from 248 (128 male and 120 female) preterm neonates born between 24 and 32 weeks' gestation. SETTING: PARTICIPANTS were recruited from 3 neonatal intensive care wards in Melbourne, Australia. PARTICIPANTS: No infant in this cohort had ambiguous genitalia or other endocrine abnormalities. All infants included in the RI determination survived beyond the equivalent of term. INTERVENTIONS: Serum was analyzed for prolactin, FSH, and LH by automated electrochemiluminescence immunoassay (Roche Cobas 8000-e601). Liquid chromatography coupled with tandem mass spectrometry was used for analysis of 17-hydroxyprogesterone, androstenedione, cortisol, cortisone, and testosterone. MAIN OUTCOME MEASURES: The robust method was applied to define the central 95% RI, after each hormone measure was transformed using a Box-Cox transformation to correct for asymmetry. RESULTS: RIs were established for 8 hormones. Gender-specific intervals were developed for FSH, LH, and testosterone. Cortisone and 17- hydroxyprogesterone required division based on gestational age, with neonates born at <30 weeks' gestation demonstrating higher levels than their older counterparts. Androstenedione, cortisol, and prolactin did not require any division within this cohort for RI assignment. CONCLUSIONS: This report provides the first characterization of serum steroids measured by mass spectrometry in preterm neonates, with the additional characterization of 3 pituitary hormones in infants born at ≤32 weeks' gestation. Use of these data allows for correct interpretation of results for very preterm neonates and reduces the risk of incorrect diagnosis due to misinterpretation of data.