Impact of Growth Hormone Supplementation on Adult Height in Turner Syndrome: Results of the Canadian Randomized Controlled Trial

908

1,259

Turner syndrome affects 25-50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and Summary of recommendationsThe recommendations (R) are worded as recommend (strong recommendation) and suggest (weak recommendation). We formally graded only the evidence underlying recommendations for therapeutic choices. The quality of evidence behind the recommendations is classified as very low (⨁◯◯◯), low (⨁⨁◯◯), moderate (⨁⨁⨁◯) and strong (⨁⨁⨁⨁). See further section 'Summary of methods used for guideline development'. Diagnosis and geneticsR 1.1. We recommend considering a diagnosis of TS in phenotypic females with a karyotype containing one X chromosome and complete or partial absence of the second sex chromosome, associated with one or more typical clinical manifestations of TS (⨁⨁⨁⨁). R 1.2. We recommend against considering a diagnosis of TS in females with one X chromosome and a deletion distal to Xq24 on the other X chromosome, and in women over the age of 50 years with less than 5% 45,X mosaicism (⨁⨁◯◯). R 1.3. We suggest that the new general surveillance management guideline applies to TS patients with any karyotype (⨁⨁◯◯). R 1.4. We recommend to consider testing for Turner syndrome (TS) in a female with typical signs (Table 2) (⨁⨁⨁⨁). R 1.5. We ...

Section: Efficacy Of Gh Treatmentmentioning

confidence: 97%

Section: Efficacy Of Gh Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

Gravholt¹,

Andersen

Conway

et al. 2017

908

1,259

“…Without GH treatment, adult women with TS are on average 20 cm shorter than women without TS (2). Although TS is not associated with GH deficiency, supraphysiological GH doses increase adult height by 5-12 cm (3,4,5). Differences in efficacy of GH treatment can be explained by age at initiation and duration of therapy, compliance, estrogen therapy regimen, and several, partly unknown, genetic factors (4,6,7).…”

Section: Introductionmentioning

confidence: 99%

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Freriks

Sas

Traas

et al. 2013

Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixtyeight women (Pl, nZ23; Ox 0.03, nZ27; and Ox 0.06, nZ18) participated in the double-blind followup study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 G4.9 cm, Ox 0.06 9.7G4.4 cm vs Pl 8.0G4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe.European Journal of Endocrinology 168 91-99

“…In past years it had been demonstrated that, in childhood, GH treatment with doses higher than those employed in GH deficiency can improve adult height (AH) in these patients (1,2,3). Therefore, it was widely accepted for many years that children with TS should be regularly treated with GH.…”

Section: Introductionmentioning

confidence: 99%

Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose

Wasniewska¹,

Aversa

Mazzanti

et al. 2013

Objective: To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0G1.7 years with a fixed GH dose of 0.33 mg/kg per week. Patients and design: After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement. Results: Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9G1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9G0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P!0.0001), with a mean H-SDS change of 0.9G0.9. However, the prevalence of patients with AH !K2 SDS (according to Sempé standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty. Conclusions: We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment.