Emma Jane Gault

Optimising management in Turner syndrome: from infancy to adult transfer

Turner syndrome can be defined as loss or abnormality of the second X chromosome in at least one cell line in a phenotypic female. The condition occurs in approximately 1 in every 2000 live female births,1 so that in the UK the prevalence for any year of life is in the region of 200 girls. The condition is much more common in utero, it being estimated that 1–2% of all conceptuses are affected, of whom only 1% will survive to term.2,3

Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial

Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14. Main outcome measure Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P=0.001, n=82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P=0.05, n=48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P<0.001). No cases of virilisation were reported. Conclusion Oxandrolone had a positive effect on final height in girls with Turner’s syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner’s syndrome. Trial registration Current Controlled Trials ISRCTN50343149.

Safety and Efficacy of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome: Evidence from Recent Studies and Recommendations for Use

There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3-4.6 cm. If Ox dosages <0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization (including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03-0.05 mg/kg/day starting from the age of 8-10 years onwards can be considered.

Improved final height in Turner's syndrome following growth-promoting treatment at a single centre.

Aims: To examine the final height (FH) outcome of girls with Turners syndrome (TS) treated at a single Scottish centre (Glasgow group), to compare it with an earlier national analysis (Scottish group) and to suggest reasons for any change. Methods: Retrospective growth and treatment data for 29 Glasgow patients were compared with those of 26 Scottish patients. Results: Age at GH start (mean ± SD) was 10.1 ± 2.6 vs 12.1 ± 1.7 y (p < 0.01) in the Glasgow versus Scottish groups, with overall duration of treatment 6.2 ± 2.4 vs 3.7 ± 1.1 y (p < 0.001) and years of GH treatment before pubertal induction 2.7 ± 2.8 vs 0.3 ± 0.8 y (p < 0.001), respectively. Pubertal induction was at a similar age: 12.7 ± 1.8 vs 12.8 ± 1.8 y (ns). FH was 151.1 ± 4.6 cm in the Glasgow group compared with 142.6 ± 5.6 cm in the Scottish group (p < 0.001), with FH ‐projected adult height (PAH) 5.7 ± 4.6 cm vs 0.6 ± 3.6 cm (p < 0.001), respectively. Univariate analysis of the Glasgow groups FH – PAH with a number of growth and treatment variables identified no statistically significant relationships.

Hormones and Genes of Importance in Bone Physiology and Their Influence on Bone Mineralization and Growth in Turner Syndrome

This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for Paediatric Endocrinology (ESPE) that was held on September 9, 2009, in New York.The program had been composed to give an update on hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome. This paper summarizes the data and highlights the main topics and discussions related to each presentation.

Cholesteatoma has a high prevalence in Turner syndrome, highlighting the need for earlier diagnosis and the potential benefits of otoscopy training for paediatricians

Girls with Turner syndrome are prone to cholesteatoma, a serious suppurative middle ear disease. We aimed to confirm its high prevalence in Turner syndrome, identify risk factors and suggest possible strategies for earlier detection.

Short Stature Screening by Accurate Length Measurement in Infants with a Birth Weight <9th Centile.

Background/Aims: Intrauterine growth restriction is an indication for growth hormone treatment. Birth length (BL) is needed to evaluate the influence of birth size on childhood short stature. However, BL is commonly measured only approximately, if at all. A single-centre study was undertaken to determine the value of measuring accurate and targeted BL and parental height (PH) for neonates with a birth weight (BW) ≤9th centile, identifying short [BL ≤-2 standard deviation scores (SDS)] and light newborns (BW ≤-2 SDS), and remeasuring short neonates at 2 years in order to detect those not showing catch-up growth. Methods: Information was collected on all live births (n = 3,798) in a single maternity unit during a 1-year period. Results: BW was ≤9th centile in 481 neonates (12.7%) of whom 47 were light but not short, 46 were short, and 60 were both light and short. Of 107 eligible infants, 57 (53%) attended the 2-year follow-up; failure of catch-up growth was identified in 6 infants (11%) of whom only 1 was already known to medical services. PH was measured in both parents of 52/153 (34%) light and/or short infants. Conclusion: Targeted and accurate BL measurement in newborns with a BW ≤9th centile is a promising alternative to the current practices. The feasibility of PH measurement after birth still requires further evaluation.