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The Journal of Clinical Endocrinology & Metabolism 90(6):3360 –3366
Copyright © 2005 by The Endocrine Society
doi: 10.1210/jc.2004-2187
Impact of Growth Hormone Supplementation on Adult
Height in Turner Syndrome: Results of the Canadian
Randomized Controlled Trial
The Canadian Growth Hormone Advisory Committee*
Background: 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.
Methods: 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䡠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.
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).
Conclusions: 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. (J Clin Endocrinol Metab 90: 3360 –3366,
2005)
Results: One hundred four patients completed the study (61 GH, 43
T
URNER SYNDROME OCCURS in one in 2000 –2500 live
female births and is associated with short stature, gonadal dysgenesis with sexual infantilism and infertility, and
a spectrum of dysmorphic features and malformations.
Without intervention, these patients attain a mean adult
height of 143 cm (4 ft 8 in.), approximately 20 cm below that
of the control female population (1). The standard replacement doses of GH used in small numbers of patients when
supplies of cadaveric GH were severely restricted did not
induce a clinically significant increase in height velocity (2).
The increased supply of GH made possible by recombinant
DNA technology allowed investigators to use higher doses
in larger groups of patients. Early enthusiasm for GH supplementation was based on studies that showed a short-term
increase in height velocity and predicted adult height (3).
More recently the adult height attained after GH supplementation was reported by numerous groups. Compared
with the height predicted or projected at the beginning of
treatment and/or to the height attained by historical control
groups of patients with Turner syndrome, GH supplementation was estimated to have no effect on adult height in some
studies (4, 5), a dramatic effect in others [mean ⫹16.9 cm in
a study in The Netherlands (6)], and a moderate effect in most
(7, 8). Factors contributing to wide variability in estimated
effectiveness include methodological difficulties in predicting or projecting adult height (9, 10), questionable appropriateness of using historical controls (11), patient selection
biases, and differences in treatment protocols (age of initiation of GH therapy, dosing regimen, adjuvant therapies).
Specifically, delaying estrogen replacement well beyond the
physiological age of thelarche was suggested as a way to
maximize any effect of GH on adult height (12).
A few protocols have included an untreated control group
for the first 12–18 months (3, 13), but maintenance of such a
group to adult height was not planned or was abandoned.
Therefore, the results from a randomized controlled study of
GH supplementation on adult height in Turner syndrome
have not been published. In 1989 a randomized, controlled
trial of GH supplementation combined with standardized
sex steroid replacement was initiated in Canada to examine
the effects of GH supplementation on adult height and psychosocial functioning in patients with Turner syndrome. We
report the results of an analysis of adult height in those
subjects who completed the core study protocol and in a
subset of those, who had at least 1 yr of follow-up beyond
protocol completion. Effects on psychosocial functioning will
be published separately.
Patients and Methods
First Published Online March 22, 2005
* A listing of The Canadian Growth Hormone Advisory Committee
appears in the Appendix.
Abbreviations: ANCOVA, Analysis of covariance; C, control group;
CI, confidence interval; SDS, sd score.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the endocrine community.
Institutional review board approval was obtained in all participating
centers across Canada. After informed consent, 154 prepubertal girls,
aged 7–13 yr, with a diagnosis of Turner syndrome documented by
peripheral blood karyotype, were enrolled. Phenotypic females with
identifiable Y chromosome material were eligible to participate if they
had undergone prior gonadectomy. Eligibility criteria included a height
less than the 10th percentile for chronological age on the growth charts
of the National Center for Health Statistics of the United States (14) and
3360
• Impact of GH Therapy on Adult Height in Turner Syndrome
an annualized height velocity less than 6.0 cm/yr during a 6-month
prerandomization period. A spontaneous or stimulated serum GH level
was 8.0 ␮g/liter or greater in all subjects. Patients with clinically significant chronic systemic illness, prior treatment with GH, anabolic
steroids, estrogens, craniospinal radiation, or inadequate thyroxine replacement for hypothyroidism were excluded. Midparental height was
ascertained where possible by measurement of biological parents.
Eligible subjects were stratified for height relative to chronological
age at entry and randomly assigned to recombinant human GH (Humatrope, Eli Lilly Canada Inc., Toronto, Ontario, Canada) by daily sc injection six times weekly (0.30 mg/kg䡠wk, maximum weekly dose 15 mg)
(GH group) or no GH treatment [control group (C)[. Girls with primary
ovarian failure received standardized sex steroid replacement as follows: ethinyl estradiol (Schering Canada Inc., Montreal, Quebec, Canada) 2.5 ␮g/d at age 13 yr, 5.0 ␮g/d at age 14 yr, and 20 ␮g on d 1–24
with medroxyprogesterone acetate 10 mg on d 15–24 of each month at
age 15 yr and thereafter. Subjects returned for follow-up every 3 months
until study completion. Routine hematology, biochemistry, and thyroid
function studies were monitored every 3 months (every 6 months in
control subjects after the first year of study). Bone age, interpreted by a
central reader using the method of Greulich and Pyle (15), was obtained
annually. Protocol completion criteria required annualized height velocity less than 2 cm/yr and bone age 14 yr or greater.
An interim analysis performed in 1996 for regulatory purposes contributed to approval of GH for treatment of short stature due to Turner
syndrome in the United States and Canada. The Data Monitoring Board
for the study subsequently made recommendations that led to the following initiatives: 1) in 1997, in support of intent-to-treat analyses, an
attempt was made to contact and obtain height measurements on all
patients who had completed the protocol or had withdrawn (1997 follow-up data); 2) analyses of patients who had completed the protocol
were updated and were presented in abstract form in 1998 (16); and 3)
a formal addendum was initiated in 1998 to assess long-term safety and
efficacy (addendum follow-up data), requiring a visit at least 1 yr after
the last core protocol visit. The two sources of follow-up data allow
comparison of true adult height with protocol-defined adult height and
an assessment of the potential for bias due to differences between patients who completed the protocol vs. those who withdrew.
The main analyses presented here are of all patients who completed the
core protocol and patients who both completed the core protocol and
J Clin Endocrinol Metab, June 2005, 90(6):3360 –3366
3361
participated in the formal addendum follow-up. All patients are analyzed
as members of the group to which they were randomized, including 10
control patients who withdrew from the core protocol and received GH
before follow-up assessment. Data are reported as mean ⫾ 1 sd unless
stated otherwise. Differences between groups at baseline and end point for
characteristics such as age and duration of therapy were assessed by oneway ANOVA or Fisher’s exact test, as appropriate. Age-specific and adult
height sd scores (SDS; height sd score) and the change in height sd scores
at protocol completion and follow-up relative to baseline (⌬ height sd score)
were calculated according to published standards for girls with Turner
syndrome (1). At protocol completion and follow-up, differences in height
variables between groups were assessed using an analysis of covariance
(ANCOVA) model with explanatory variables of treatment, baseline height
SDS, baseline height SDS by treatment interaction, baseline age, and baseline age by treatment interaction. Explanatory variables were removed from
the model when not significant; design factors were always retained. This
is not the a priori model defined in the protocol but has greater explanatory
power. The a priori model and supportive analyses of protocol-complete
and intent-to-treat populations, including analyses of available follow-up
data on patients who withdrew from the protocol, led to very similar
efficacy estimates and statistical inferences.
Results
An outline of study participation is presented in Fig. 1. One
hundred four girls completed the protocol (GH 61, C 43) and
50 withdrew from participation (GH 15, C 35). A common
reason for withdrawal was by patient decision within 6
months of randomization (GH 3, C 16).
There were some observed differences between patients
who completed the protocol and those who withdrew when
treatment regimen is taken into account. Control patients
who stayed in the protocol had baseline height SDS of ⫺0.1,
compared with ⫺0.2 for patients who withdrew. GH patients
who stayed in the protocol had baseline height SDS of ⫺0.2,
compared with 0.3 for patients who withdrew.
FIG. 1. Outline of study participation.
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J Clin Endocrinol Metab, June 2005, 90(6):3360 –3366
Efficacy analysis
Baseline characteristics and efficacy results are summarized
in Table 1. There were no statistically significant differences
between the GH and C groups at baseline. At protocol completion and addendum follow-up, the GH and C groups were
comparable for bone age and duration of follow-up.
For those patients who completed the protocol, Fig. 2
depicts the individual heights at baseline, protocol completion, and follow-up. At protocol completion, 17 of 61 GH
recipients (27.9%) exceeded the 90th percentile for adult
women with Turner syndrome, compared with one of the 43
controls (2.3%). The corresponding numbers at follow-up
were 14 of 40 (GH, 35.0%) and 2 of 19 (C, 10.5%). At followup, 100% of GH recipients (40/40) had increased height SDS,
compared with 47.4% of controls (9/19).
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 from
the addendum follow-up, 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).
Estimates of efficacy, based on ANCOVA models, were
consistent at protocol completion and follow-up. The difference in adult height due to GH, estimated by ANCOVA, was
• Impact of GH Therapy on Adult Height in Turner Syndrome
⫹7.2 cm [95% confidence interval (CI) 6.0 – 8.5 cm] at protocol
completion and ⫹7.3 cm (95% CI 5.3–9.2 cm) at follow-up,
each P ⬍ 0.001, compared with control patients. Expressed
in adult height SDS, this height difference was ⫹1.1 sd (95%
CI 0.9 –1.3 sd at protocol completion, 0.7–1.4 sd at follow-up,
each P ⬍ 0.001, compared with control patients).
Figure 3 shows, at most recent available height for all
patients who completed the protocol, the change in agespecific height SDS from baseline vs. baseline age. In the
ANCOVA model of Table 1, applied to most recent height
data of all patients who completed the protocol, the benefit
of each year of earlier GH initiation on height SDS was ⫹0.22
sd (P ⬍ 0.001, 95% CI 0.10 – 0.33 sd) or ⫹1.5 cm/yr, i.e. girls
who began GH at an earlier age had greater increase in
height, although this age effect is highly variable between
patients.
At protocol completion and follow-up, the GH group consistently achieved greater height gain from baseline than
control subjects, regardless of height SDS at baseline. The
impact of baseline height SDS on change in height SDS was
assessed using regression models that also included baseline
age, and results were inconclusive.
Of patients who reached age 13 yr during the core protocol
(71 GH, 52 C), 13 patients (9 GH, 4 C) were noted by inves-
TABLE 1. Patient characteristics and efficacy analysis
Treatment group (mean ⫾
Baseline characteristicsb
Protocol complete (n)
Baseline age (yr)
Baseline bone age (yr)
Baseline height (cm)
Baseline height SDS (age-specific Turner)
Adjusted midparental height (cm)c
45, X Karyotype (%)
Completion characteristics
Protocol complete (n)
Time since randomization (y)
Age (yr)
Bone age (yr)
Height (cm)
Height SDS (age-specific Turner)
Height SDS (adult Turner)
Change in height (cm)
Change in height SDS (age-specific Turner)
Addendum follow-up characteristics
Protocol complete with addendum follow-up (n)
Time since randomization (yr)
Age (yr)
Bone age (yr)
Height (cm)
Height SDS (age-specific Turner)
Height SDS (adult Turner)
Change in height (cm)
Change in height SDS (age-specific Turner)
SD)
GH
C
GH effecta
[mean (95% CI)]
61
10.3 ⫾ 1.8
8.8 ⫾ 1.4
119.1 ⫾ 8.5
⫺0.2 ⫾ 0.9
160.7 ⫾ 6.2
62.3
43
10.9 ⫾ 1.7
8.9 ⫾ 1.3
122.0 ⫾ 7.8
⫺0.1 ⫾ 0.8
159.3 ⫾ 5.8
58.1
–
–
–
–
–
–
–
61
5.7 ⫾ 1.6
16.0 ⫾ 0.8
14.4 ⫾ 0.8
147.5 ⫾ 6.1
1.4 ⫾ 1.0
0.7 ⫾ 0.9
28.3 ⫾ 8.9
1.6 ⫾ 0.6
43
5.7 ⫾ 1.6
16.5 ⫾ 0.9
14.5 ⫾ 0.9
141.0 ⫾ 5.4
0.2 ⫾ 0.9
⫺0.3 ⫾ 0.8
19.0 ⫾ 6.1
0.3 ⫾ 0.4
–
–
–d
⫺0.1 (⫺0.5, 0.3)
7.2 (6.0, 8.4)e
1.2 (1.0, 1.5)e
1.1 (0.8, 1.3)e
7.2 (6.0, 8.3)e
1.3 (1.1, 1.5)e
40
10.6 ⫾ 1.7
20.7 ⫾ 2.5
15.1 ⫾ 1.0
149.0 ⫾ 6.4
0.9 ⫾ 0.9
0.9 ⫾ 0.9
30.3 ⫾ 8.3
1.1 ⫾ 0.5
19
10.7 ⫾ 1.4
21.2 ⫾ 2.0
15.2 ⫾ 1.0
142.2 ⫾ 6.6
⫺0.1 ⫾ 1.0
⫺0.1 ⫾ 1.0
21.6 ⫾ 6.2
0.0 ⫾ 0.5
–
–
–
0.0 (⫺0.6, 0.6)
7.3 (5.4, 9.2)e
1.1 (0.8, 1.4)e
1.1 (0.8, 1.4)e
7.3 (5.4, 9.1)e
1.1 (0.8, 1.4)e
a
ANCOVA model with treatment, baseline height SDS, baseline height SDS by treatment interaction, baseline age, and baseline age by
treatment interaction. Explanatory variables were removed from the model when not significant. GH effect is estimated by differences of
least-squares means for treatment.
b
Baseline for patients who completed the protocol. Baseline data for patients who also had follow-up are very similar. No baseline
characteristics differed at P ⬍ 0.05.
c
Adjusted midparental height ⫽ [(Father height ⫺ 13 cm) ⫹ Mother height]/2.
d
Age at protocol completion was significantly different between control and GH, P ⫽ 0.002. This reflects the similar numerical difference
at baseline and completion, and the lower SD at completion due to the narrower age range.
e
P ⬍ 0.001 based on least-squares means differences in ANCOVA model. Other entries not significant.
• Impact of GH Therapy on Adult Height in Turner Syndrome
J Clin Endocrinol Metab, June 2005, 90(6):3360 –3366
3363
FIG. 2. Height at baseline, protocol completion, and addendum follow-up (at least 1 yr after completion) vs. age, plotted with 10th, 50th, and
90th percentile growth curves for Turner syndrome (1) for patients who completed the core protocol. Horizontal dashed line, Height of 5 feet
(152.4 cm); open circles, control subjects; solid circles, GH-treated subjects.
tigators to have secondary sexual characteristics without hormone replacement. Change in height SDS from baseline to
latest available height for patients with such findings was
⫹1.1 sd (GH) and ⫹0.2 sd (C) and for those without ⫹1.2 sd
(GH) and ⫹0.1 sd (C). The small sample size of this population precludes any formal conclusions regarding differential effect of GH supplementation in girls with sufficient
ovarian function to enter puberty without sex steroid replacement therapy.
It is naturally a concern whether those patients who completed both the protocol and the follow-up addendum are
representative of the overall study population. In addition to
follow-up data collected for patients who completed the protocol, follow-up data beyond the discontinuation visit were
obtained for 70% of patients who withdrew from the protocol
(from Fig. 1, 13 of 15 GH, 22 of 35 C). Figure 4 summarizes
the latest available data on all 154 patients randomized in the
study. The available data on patients who had addendum
follow-up, 1997 follow-up only, or core protocol data only
suggest that there is no inherent difference in these groups,
aside from nature of follow-up. Two GH patients lost height
sd by the time of follow-up but in both cases had participated
in the study for less than 7 months. Seven control patients
who withdrew from the study had height gain at follow-up
of more than ⫹1 sd; in all but one case, these patients had
received GH therapy after leaving the study.
To verify robustness of results, numerous supportive analyses of patients who withdrew from study, and intent-totreat analyses, were undertaken. For instance, one support-
ive analysis assumed, for patients with no follow-up data,
that all GH patients (n ⫽ 2) lost 0.5 sd, whereas all control
patients (n ⫽ 13) gained 0.5 sd after they were last observed.
Even under this conservative assumption, the mean difference in height gain between the GH and control groups was
greater than 0.7 sd (P ⬍ 0.001). This analysis, in particular,
addresses concerns about preferential dropout of shorter
control patients. This and similar analyses demonstrate that
the impact of differential withdrawal from the two treatment
groups was insufficient to change the overall efficacy
conclusions.
Adverse events and safety
In 138 patients for whom postbaseline data are available,
a significant difference in treatment emergent adverse events
between GH (n ⫽ 74) and C (n ⫽ 64) subjects was noted as
follows: 1) surgical procedures (37 GH, 17 C, P ⫽ 0.005); 2)
otitis media (35 GH, 17 C, P ⫽ 0.014); 3) ear disorder (15 GH,
4 C, P ⫽ 0.024); 4) joint disorder (10 GH, 2 C, P ⫽ 0.036); 5)
respiratory disorder (8 GH, 1 C, P ⫽ 0.037); 6) sinusitis (14
GH, 4 C, P ⫽ 0.041); and 7) goiter (0 GH, 4 C, P ⫽ 0.044). Death
from ruptured aortic aneurysm occurred in a single control
subject. Two GH recipients withdrew because of an adverse
event, one because of elevated transaminase levels and one
because of intracranial hypertension. After protocol completion, there was no significant difference in auditory acuity
(conductive or neurosensory) between groups (data not
shown). There were no significant between-group differ-
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J Clin Endocrinol Metab, June 2005, 90(6):3360 –3366
• Impact of GH Therapy on Adult Height in Turner Syndrome
FIG. 3. Change in age-specific height SDS for Turner syndrome (1) at most recent available height vs. age at baseline for all patients who
completed the core protocol. Horizontal dashed line, No change in height SDS; open circles, control patients; solid circles, GH-treated patients.
ences in change from baseline to end point in fasting blood
glucose, hemoglobin A1c, serum T4, or TSH (data not shown).
Discussion
In the present study of patients with Turner syndrome,
after a mean of 5.7 yr of treatment, the effect of GH supplementation on adult height, estimated by ANCOVA, was ⫹7.2
cm (95% CI 6.0 – 8.5 cm) at protocol completion and ⫹7.3 cm
(95% CI 5.3–9.2 cm) at follow-up, each P ⬍ 0.001, compared
with control patients. Whereas this estimate is similar in
direction and magnitude to that of most nonrandomized
studies, it should be emphasized that this is the first demonstration of the efficacy of GH supplementation by a trial
that maintained a parallel control group to adult height. As
found in many GH studies, there is high individual variability in the magnitude of response to GH, although in our
study all GH-supplemented patients who completed the protocol had a higher Turner-specific height SDS at last available
measurement than at start of treatment (Fig. 4). Even in the
nonrandomized studies that have reported very positive
mean outcomes, a small proportion of patients were found
not to respond to GH supplementation at all (12). The reason
for the uniformly positive height outcome in the present study
is unclear but may relate to greater adherence to treatment in
patients who complete randomized, controlled trials (17).
The pubertal induction protocol allowed thelarche and
menarche to occur about 2 sd beyond the mean age of oc-
currence of these important milestones of adolescence. This
sex steroid replacement protocol may have a positive impact
on psychosocial adaptation and bone health, two important
challenges for patients living with Turner syndrome (18, 19).
Whereas we began sex steroid replacement at a younger age
than in some other published studies (4 –9), our patients experienced similar magnitude of height gain from GH therapy. Our
results and those of a recent observational study (20) with a very
low initial dose of ethinyl estradiol do not support the practice
of delaying pubertal induction further, especially in those girls
who request age-appropriate feminization.
The GH recipients had significantly more ear disorders,
otitis media, and surgical procedures (mostly ear, nose, and
throat surgeries) than the control patients. Possible explanations for these observations could include an increase in
the size of tonsils and adenoids with GH treatment (21) or a
reporting bias due to the unblinded design of the present
study. Given the heavy burden that hearing loss represents
for many adult women with Turner syndrome (22), formal
audiometry was undertaken in this study starting in 1998;
there were no differences in auditory acuity between GH and
control patients. The increase in joint disorders observed in
the GH group has also been observed in dose-titration studies in GH-deficient adults (23).
The impact of age at initiation of GH treatment on adult
height remains controversial, with some studies suggesting
that earlier is better (13, 24) and some finding no effect (20).
• Impact of GH Therapy on Adult Height in Turner Syndrome
J Clin Endocrinol Metab, June 2005, 90(6):3360 –3366
3365
FIG. 4. Change in age-specific height SDS for Turner syndrome (1) at most recent available height vs. time on core protocol for all 154 randomized
patients. Horizontal dashed line, No change in height SDS; open circles, control patients; solid circles, GH-treated patients; asterisk, control
patients who received GH after leaving core protocol.
Our own results show a significant, although variable advantage to starting at 7– 8 yr rather than at 12–13 yr (Fig. 3).
Our study design cannot distinguish between an effect of age
of initiation, total duration of GH therapy, or duration of GH
therapy before starting sex steroid replacement. Whether
starting earlier than age 7 yr would result in a greater gain
in adult height remains to be demonstrated. In one study (25),
GH accelerated bone maturation in very young children with
Turner syndrome. In addition, young children with Turner
syndrome do not yet perceive their height as a problem and
may not easily accept daily injections (26). Analyses of the
effect of baseline height SDS on change in height SDS due to
GH therapy were inconclusive.
Statistical modeling leads to consistent estimation, at protocol completion and follow-up, of height gain due to GH
therapy. However, patients continued to grow after protocol
completion. Accordingly, age-specific height SDSs and adult
height SDSs differ at time of completion. The follow-up data
resolve this issue by examining patients when growth has
either ceased or is extremely slow. At follow-up, we see that
the age-specific and adult SDSs are the same. Moreover, our
control patient population was very similar to the standards
established by Lyon et al. (1) in attained height SDS (⫺0.1 ⫾
1.0, Turner adult) and the mean; control patients attained
their projected height sd (⌬ ⫽ 0.0 ⫾ 0.5). This is one reason
we believe that the patients who participated in the addendum follow-up accurately represent the overall study pop-
ulation. These observations show that, for the most accurate
evaluation of the impact on adult height of therapies for short
stature, studies should follow patients until cessation of
growth, even if treatment is stopped earlier.
In summary, we report the first conclusive evidence, based
on a randomized, controlled trial to adult height, of a positive
impact of GH supplementation on the adult height of Turner
syndrome patients. The benefits of GH supplementation
need to be balanced against the cost of therapy and the need
for daily sc injections over a period of many years. The
differences in the magnitude of the height gain observed in
our study and those reported by others may reflect differences in study design, patient selection, duration of GH supplementation, GH dosage, concurrent anabolic steroid administration, or timing and dosage of estrogen replacement.
The impact of GH on psychosocial adaptation and adult
health outcomes in these patients requires further study. In
conclusion, GH supplementation with induction of secondary sexual characteristics at a near physiological age increased the mean adult height of girls with Turner syndrome.
Patients and parents should establish with their physician
realistic expectations of GH supplementation. The results of
the present analysis provide a strong justification to offer the
option of GH supplementation to school-age girls with
Turner syndrome and an accurate estimate of what can be
expected from this intervention.
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• Impact of GH Therapy on Adult Height in Turner Syndrome
Appendix
Steering and Writing Committees: D. K. Stephure (Chairman and Principal Investigator 1994 to present) (University of Calgary); G. Anglin
(Statistics) (Eli Lilly Canada Inc.); J. Chipman (Eli Lilly & Co.); D. Daneman (University of Toronto); H. J. Dean (University of Manitoba); H. J.
Guyda (McGill University); F. J. Holland (Principal Investigator 1989 –
1994) (McMaster University); C. Quigley (Eli Lilly & Co.); G. Van Vliet
(University of Montreal).
Writing Committee: D. K. Stephure (University of Calgary), G. Anglin
(Eli Lilly Canada Inc.), G. Van Vliet (University of Montreal).
Data Monitoring Board: J. G. Hall (Chairman) (University of British
Columbia); M. A. Preece (Institute of Child Health); W. Taylor (McMaster University).
Bone Age Interpretation: A. Daneman, B. Riley (University of Toronto).
The following investigators and academic institutions also participated in this research: S. R. Salisbury (Dalhousie University); J. A. Curtis
(Memorial University); F. Szots (Laval University); R. D. Barnes, L.
Legault, C. Polychronakos, C. Rodd (McGill University); A. B. MacMillan, J. A. Vander Meulen (McMaster University); D. S. Alexander
(Queens University); R. M. Couch, E. E. McCoy (University of Alberta);
D. Metzger, H. F. Kitson, L. L. Stewart, W. J. Tze (University of British
Columbia); S. P. Taback (University of Manitoba); R. Collu, C. L. Deal,
C. Huot (University of Montreal); K. A. Faught, M. L. Lawson, S. E.
Muirhead (University of Ottawa); T. B. Best, G. A. Bruce (University of
Saskatoon); K. Khoury (University of Sherbrooke); J. D. Bailey, R. M.
Ehrlich, K. Perlman, J. Rovet (University of Toronto); B. C. Boulton
(University of Victoria); C. L. Clarson, M. R. F. Jenner (University of
Western Ontario).
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Acknowledgments
17.
We thank the patients and their families for their commitment to the
study and many other individuals in a variety of roles who contributed
to the conduct of this study over the course of 15 yr.
18.
Received November 8, 2004. Accepted March 14, 2005.
Address all correspondence and requests for reprints to: David K.
Stephure, M.D., Department of Pediatrics, University of Calgary, Alberta Children’s Hospital, 1820 Richmond Road SW, Calgary, Alberta,
Canada T2T 5C7. E-mail: [email protected].
This work was supported by Eli Lilly Canada, Inc.
19.
20.
21.
References
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syndrome. Arch Dis Child 60:932–935
2. Tanner JM, Whitehouse RH, Hughes PC, Vince FP 1971 Effect of human
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