Adult Height In Turner Syndrome Research Articles

Adult Height in 299 Patients with Turner Syndrome with or without Growth Hormone Therapy: Results and Literature Review

Context: Treatment with growth hormone (GH) is considered effective in improving adult height (AH) in Turner syndrome (TS). However, there are few studies comparing AH between treated patients and a concurrent untreated group. Objective: To assess the efficacy of GH treatment in improving AH in TS and to review previous published studies with treated and untreated groups. Participants and Methods: We retrospectively analyzed clinical data and AH of a large cohort of GH-treated (n = 168) and untreated (n = 131) patients with TS. Data are shown as median and interquartile range (IQR). We assessed pretreatment variables related with AH and compared our results with 16 studies that also included an untreated group. Results: The GH-treated group was 6.2 cm taller than the untreated group (AH = 149 cm [IQR 144.5–152.5 cm] vs. 142.8 cm [IQR 139–148 cm], p < 0.001) after 4.9 years of GH treatment with a dose of 0.35 mg/kg/week. AH SDS corrected for target height (TH) was 7.2 cm higher in GH-treated patients. AH SDS ≥−2 was more frequent in GH-treated patients (43%) than in untreated patients (16%, p < 0.001). AH SDS was also more frequently within the TH range in the GH-treated group (52%) than in the untreated group (15%, p < 0.001). Height SDS at start of GH therapy and TH SDS were positively correlated with AH (p < 0.001; R² = 0.375). Considering the current result together with previous similar publications, a mean AH gain of 5.7 cm was observed in GH-treated (n = 696) versus untreated (n = 633) patients. Conclusions: Our study strengthens the evidence for efficacy of GH therapy in patients with TS from different populations.

Growth Hormone Supplementation and Psychosocial Functioning to Adult Height in Turner Syndrome: A Questionnaire Study of Participants in the Canadian Randomized Trial.

Despite the long-held belief that growth hormone supplementation provides psychosocial benefits to patients with Turner syndrome (TS), this assumption has never been rigorously tested in a randomized control trial. As a sub-study of the Canadian growth-hormone trial, parent-, and patient-completed standardized questionnaires were used to compare 70 girls with TS who received injections (GH group) and 61 similarly followed untreated TS controls (C) on multiple facets of psychosocial functioning. Questionnaires were given (i) at baseline (session 1, mean age = 10.4 y), (ii) before estrogen therapy for puberty induction (session 2, mean age = 13.0 y), (iii) after 1 year of estrogen therapy (session 3, mean age = 14.4 y), and (iv) when growth stopped (session 4, mean age = 16.3 y). Groups were compared for multiple facets of psychosocial function within social, behavioral, self-esteem, and academic domains. Results were also correlated with indices of adult height. We found no global (i.e., across-session) group differences on any scales or subscales of the four domains. In both GH and C groups, age-related improvements were seen for social problems, externalizing behavior problems, and school functioning and age-related declines for social competence and social relations. Both parents and patients claimed GH received less teasing than C but C had more friends than GH. Results from analyses conducted within individual sessions showed that while GH at early sessions claimed to be more popular, more socially engaged, better adapted, and to have higher self-esteem than C, C was reported to be less anxious, depressed, and withdrawn than GH at adult height. The correlation analyses revealed different effects of adult height and height gain on outcome for the two groups. In GH, both height parameters were correlated with multiple parent- and/or self-reported indices from the four psychosocial domains, whereas in C, only adult height and two indices (viz., total self-concept and school functioning), were correlated. The observed modest gains in psychosocial functioning for patients with TS treated with GH highlight the need for alternative approaches to assist them in coping with the challenges of their condition.

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. We conducted a national observational multicenter study. Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.

Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis.

Turner syndrome is a chromosomal abnormality in which there is complete or partial absence of the X chromosome. Turner syndrome effects 1 in every 2000 live births. Short stature is a cardinal feature of Turner Syndrome and the standard treatment is recombinant human growth hormone. When growth hormone is started at an early age a normal adult height can be achieved. With delayed diagnosis young women with Turner Syndrome may not reach a normal height. Adjuvant therapy with oxandrolone is used but there is no consensus on the optimal timing of treatment, the duration of treatment and the long term adverse effects of treatment. The objective of this review and meta-analysis is to examine the effect of oxandrolone on adult height in growth hormone treated Turner syndrome patients. Eligible trials were identified by a literature search using the terms: Turner syndrome, oxandrolone. The search was limited to English language randomized-controlled trials after 1980. Twenty-six articles were reviewed and four were included in the meta-analysis. A random effects model was used to calculate an effect size and confidence interval. The pooled effect size of 2.0759 (95 % CI 0.0988 to 4.0529) indicates that oxandrolone has a positive effect on adult height in Turner syndrome when combined with growth hormone therapy. In conclusion, the addition of oxandrolone to growth hormone therapy for treatment of short stature in Turner syndrome improves adult height. Further studies are warranted to investigate if there is a subset of Turner syndrome patients that would benefit most from growth hormone plus oxandrolone therapy, and to determine the optimal timing and duration of such therapy.

Prospective Study Confirms Oxandrolone-Associated Improvement in Height in Growth Hormone-Treated Adolescent Girls with Turner Syndrome

Background/Aims: Untreated girls with Turner syndrome (TS) have growth failure, and adult height is, on average, 20 cm less than predicted height. Treatment with growth hormone (GH) is now standard of care. The objective of this study was to investigate the benefit of adding oxandrolone (Ox) to GH in a long-term, randomized, placebo (Pl)-controlled prospective trial to near adult height in TS. Methods: Prospective, randomized, Pl-controlled study: 76 girls with TS (ages 10–14.9 years) were randomized to receive Ox (0.06 mg/kg/day) or Pl in combination with GH (0.35 mg/kg/week, daily) over 2 years. Auxologic data, breast and pubic hair Tanner stages, and hormone and lipid levels were measured. Subjects who chose to continue were followed in a 2-year double-blind extension, also received estrogen therapy (years 3, 4), and had dual-energy X-ray absorptiometry evaluation of bone density (years 3, 4). Results: At year 4, the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [26.2 ± 6.7 vs. 22.2 ± 5.1 cm, analysis of covariance (ANCOVA) p < 0.001; 1.8 ± 0.9 vs. 1.2 ± 0.7 standard deviation scores, ANCOVA p < 0.001]. Bone mineral density (BMD) of the wrist (0.51 ± 0.17 vs. 0.54 ± 0.05 g/cm²) and spine (0.91 ± 0.34 vs. 0.96 ± 0.13 g/cm²) in the GH/Ox versus GH/Pl groups was similar after 4 years. Breast development was slower in the GH/Ox versus GH/Pl group [year 4: Tanner stage 2.9 ±1.3 (Ox) vs. 4.1 ± 1.3 (Pl), p = 0.003], and menarche was approximately 1 year later. Conclusions: The addition of Ox to GH at mean age 12.0 ± 1.7 year augmented height gain after 4 years of treatment, slowed breast development and did not affect BMD in girls with TS. Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study.

Efficacy and Safety of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome

GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. A randomized, placebo-controlled, double-blind, dose-response study was performed in 10 centers in The Netherlands. One hundred thirty-three patients with TS were included in age group 1 (2-7.99 yr), 2 (8-11.99 yr), or 3 (12-15.99 yr). Patients were treated with GH (1.33 mg/m(2) . d) from baseline, combined with placebo (Pl) or Ox in low (0.03 mg/kg . d) or conventional (0.06 mg/kg . d) dose from the age of 8 yr and estrogens from the age of 12 yr. Adult height gain (adult height minus predicted adult height) and safety parameters were systematically assessed. Compared with GH+Pl, GH+Ox 0.03 increased adult height gain in the intention-to-treat analysis (mean +/- sd, 9.5 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.02) and per-protocol analysis (9.8 +/- 4.9 vs. 6.8 +/- 4.4 cm, P = 0.02). Partly due to accelerated bone maturation (P < 0.001), adult height gain on GH+Ox 0.06 was not significantly different from that on GH+Pl (8.3 +/- 4.7 vs. 7.2 +/- 4.0 cm, P = 0.3). Breast development was slower on GH+Ox (GH+Ox 0.03, P = 0.02; GH+Ox 0.06, P = 0.05), and more girls reported virilization on GH+Ox 0.06 than on GH+Pl (P < 0.001). In GH-treated girls with TS, we discourage the use of the conventional Ox dosage (0.06 mg/kg . d) because of its low benefit to risk ratio. The addition of Ox 0.03 mg/kg . d modestly increases adult height gain and has a fairly good safety profile, except for some deceleration of breast development.

Predicting adult height in Turner syndrome

Like Wasniewska et al. (1) we also have an interest in the effect of growth hormone (GH) on growth and final adult height in Turner syndrome. Predicting final adult height in any individual is far from an exact science, but we believe that Wasniewska’s calculations are flawed; first due to the inappropriate use of height standard deviation scores (SDS), and secondly due to the fact that the girls in their study, after their initial measurement, were being treated with GH. Wasniewska et al. calculated height SDS in their patients using the data of Sempe et al. 1979 (2). These data, as stated by Wasniewska and colleagues, are from ‘normal girls’. This SDS is then used in the equation published by Lyon et al. (3) to derive a predicted adult SDS, which is then converted back into a height via reference to the data of Sempe et al. (2). The important point to note is that the Lyon equation is based on SDS calculated using data derived from children with Turner syndrome.

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

A randomized, controlled trial of GH supplementation to adult height in girls with short stature due to Turner syndrome was conducted in Canada. We report results in subjects who completed the protocol and subjects who participated in follow-up. One hundred fifty-four girls with Turner syndrome, aged 7-13 yr, were randomly assigned to one of two groups: 1) GH by sc injection six times per week (0.30 mg/kg.wk), and 2) control (C), no GH treatment. Both cohorts received standardized sex steroid replacement starting at a chronological age of 13 yr. Subjects were followed until protocol completion, defined as height velocity less than 2 cm/yr and bone age 14 yr or greater. A subsequent protocol addendum requested follow-up safety and efficacy assessment in all patients at least 1 yr after the last core protocol visit. One hundred four patients completed the study (61 GH, 43 C), and 50 withdrew (15 GH, 35 C). At protocol completion, mean heights were 147.5 +/- 6.1 (GH) and 141.0 +/- 5.4 cm (C), respectively (P < 0.001). Of those who completed the protocol, 59 (40 GH, 19 C) had height data at least 1 yr after protocol completion; in that group, mean heights were 149.0 +/- 6.4 (GH) and 142.2 +/- 6.6 cm (C), respectively (P < 0.001). At protocol completion and follow-up, the mean height gain due to GH, estimated by analysis of covariance, was +7.2 cm (confidence interval 6.0, 8.4) and +7.3 cm (confidence interval 5.4, 9.2), respectively (both P < 0.001). This is the first evidence from a randomized, controlled trial to adult height that GH supplementation with induction of puberty at a near physiological age increases the adult height of girls with Turner syndrome.

Final Height in Girls with Turner Syndrome after Growth Hormone Treatment. Experience at National Children's Hospital.

Twenty-four patients with Turner syndrome were treated with human growth hormone (GH) and reached their final height. Mean age was 11.7 years and mean height SDS was 0.28 SD for Japanese Turner standard at the start of GH treatment. Mean duration of GH treatment was 6.6 years and mean age at discontinuation of GH treatment was 18.6 years. Final height of all the patients was 146.9 ± 4.2 cm (140.5∼153.9 cm). Since predicted adult height (PAH) was 139.4 ± 5.8 cm (131.8∼155.0 cm), the benefit from growth-promoting therapy (final height - PAH) was 7.5 ± 4.6 cm (-1.4∼+15.2 cm). The final height in 10 patients (42%) exceeded the -2.0 SD value (147.9 cm) for normal girls. It can be concluded that the adult height in Turner syndrome was improved by GH treatment. However, final height was improved by starting pubertal induction later in addition to GH treatment in Japan. Early diagnosis and initiation of treatment with a higher dose of GH is important for adequate pubertal induction and final height.

Adult height in Turner syndrome: results of a multinational survey 1993.

Under the auspices of ESPE/LWPES, a survey on spontaneous adult height in patients with Turner syndrome was conducted in 12 European countries. A total of 661 patients (45,X = 51%) with a median age of 23.6 years (range: 16-63) who had never received any growth-promoting treatment until the age of 14 had reached a mean height of 144.3 +/- 6.7 cm. There was no height difference between those (n = 220) who had received oxandrolone and/or estrogen after the age of 14 years and those (n = 441) who never received any treatment until the age of 20. On average, there was no major gain in height after an age of 16 years. The height achieved was positively associated with the height of normal women in the underlying population. There was a high positive correlation (r = 0.436; p < 0.0001) between adult height and target height in adults never treated. A positive correlation of these parameters was present irrespective of karyotype (45,X vs. 'others') or treatment with oxandrolone/estrogen. The findings strengthen the observations on height development from national studies.

Prediction of Adult Height in Turner Syndrome

Prediction of Adult Height in Turner Syndrome

PEDICTION OF ADULT HEIGHT IN TURNER SYNDROME

Predictions of adult height in girls with Turner Syndrome using established methods, projected height (PROJ), predicted height (PRED), and index of potential height (IPH), were compared to a novel method (KIGS):KIGS (as ht SDS) = ht SDS (using Ranke standards) - BA SDS for CA. BA SDS for CA was calculated from Greulich and Pyle BAs of 640 untreated girls with Turner Syndrome entered into the KabiPharmacia International Growth Study. Adult height predictions for 245 girls at onset of GH treatment (mean ± SD) were 145.5 cm ± 6.0 (PROJ), 144.9 cm ± 6.4 (PRED), 153.7 cm ± 7.2 (IPH), and 143.5 cm ± 6.4 (KIGS). 26 girls treated for 3 years with growth hormone alone had increases in height prediction of 8.7 cm ± 4.3 (PROJ), 5.6 cm ± 5.1 (PRED), 7.2 cm ± 6.0 (IPH), and 3.3 cm ± 6.4 (KIGS). Height predictions for 15 girls treated with combinations of growth hormone, oestrogen and oxandrolone were then compared to their own achieved adult heights: at 2 years into treatment, PROJ, PRED, and IPH already overestimated adult height by 1.8 cm ± 2.5, 2.5 cm ± 1.3, and 13.8 cm ± 1.6, respectively, and KIGS underpredieted by 2.5 ± 1.5 cm. We conclude that the established methods, especially IPH, tend to overpredict adult height in Turner Syndrome, and that the KIGS method is more conservative.

Adult height in Turner syndrome with and without androgen therapy

Adult heights of 66 individuals with karyotype documentation of Turner syndrome were analyzed. The mean adult height of 29 individuals given growth-promoting hormones, oxandrolone or fluoxymesterone, did not differ significantly from that of 37 untreated subjects (148.1 +/- 4.7 vs 146.3 +/- 5.5 cm, respectively). The type of X chromosome abnormality did not influence the mean adult height. No significant deleterious effect on height was seen with earlier induction of puberty with estrogens. Parental heights did not appear to influence final adult height. Based on this study, the use of androgens to increase adult height in Turner syndrome cannot be recommended and there appears to be no benefit in delaying induction of puberty with exogenous hormones beyond the mid-teens (14 to 16 years).