The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 12 4622-4628
Copyright © 1999 by The Endocrine Society
Body Proportions during Long-Term Growth Hormone Treatment in Girls with Turner Syndrome Participating in a Randomized Dose-Response Trial1
Theo C. J. Sas,
Willem-Jan M. Gerver,
Rob de Bruin,
Theo Stijnen,
Sabine M. P. F. de Muinck Keizer-Schrama,
Tim J. Cole,
Arne van Teunenbroek and
Stenvert L. Drop
Department of Pediatrics, Division of Endocrinology (Th.C.J.S.,
S.M.P.F.M.K.-S., A.T., S.L.S.D.) Sophia Children’s Hospital, 3015 GJ
Rotterdam, The Netherlands; Academic Hospital Maastricht (W.J.G., R.B.)
and the Department of Epidemiology and Biostatistics, Erasmus
University (T.S.), Rotterdam, The Netherlands; and the
Department of Epidemiology and Public Health, Institute of Child Health
(T.J.C.), London, United Kingdom
Address all correspondence and requests for reprints to: Theo C. J. Sas, M.D., Division of Endocrinology, Sophia Children’s Hospital, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
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Abstract
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To assess body proportions in girls with Turner syndrome (TS) during
long term GH treatment, height, sitting height (SH), hand (Hand) and
foot (Foot) lengths, and biacromial (Biac) and biiliacal (Biil)
diameters were measured in 68 girls with TS participating in a GH
dose-response trial. These previously untreated girls with TS, aged
2–11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4
IU/m2·day; group B, first year 4 and thereafter 6
IU/m2·day; group C, first year 4, second year 6, and
thereafter 8 IU/m2·day. Seven-year data were evaluated to
assess the effect of GH treatment on body proportions during childhood.
In addition, data from all girls who had reached adult height were
evaluated to determine the effect on the adult body proportions. All
results were adjusted for age and sex and expressed as SD
scores using reference values of healthy Dutch girls. To
describe the proportions of SH, Hand, Foot, Biac, and Biil to height,
these values were adjusted for the SD score of height and
were expressed as shape values, using the formula, e.g.
for SH: shape SH = (SH SD score - height
SD score)/
(2 - 2 x correlation coefficient
between SH and height in the reference population). Furthermore,
SD scores using references of untreated girls with TS were
calculated for height and SH. Values less than -2 or more than +2 were
considered outside the normal range.
At baseline, the shape values of all measurements were significantly
higher than zero, but most mean shape values were still within the
normal range. Seven-year data of 64 girls and adult height data of 32
girls showed that an increase in height was accompanied by an even
higher increase in Foot, resulting in mean SD scores above
zero and shape values of +2 and higher. The increase in the shape value
of Foot was significantly higher in groups B and C compared to that in
group A after 7 yr of GH treatment, but there were no significant
differences between the GH dosage groups in the girls who had reached
adult height. The shape values of SH had decreased to values closer to
zero after reaching adult height, especially in group A. A similar
pattern in the relationship of SH to height was seen using references
of girls with TS. No significant changes in the other proportions were
found after reaching adult height.
In conclusion, on the average, untreated girls with TS have
relatively large trunk, hands, and feet, and broad shoulders and pelvis
compared to height. The increase in height after long term GH treatment
is accompanied by an even higher increase in Foot and a moderate
improvement of the disproportion between height and SH. Recently
published reference data from untreated adults with TS and the results
of a different patient group receiving a comparable GH dosage suggest
that the disproportionate growth of feet has to be considered a part of
the natural development in TS, but might be influenced by higher GH
dosages. The development of large feet can play a role in the decision
of the girl to discontinue GH treatment in the last phase of growth.
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Introduction
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GROWTH FAILURE and subsequently short adult
stature are two of the main features in Turner syndrome (TS) (1, 2).
Although these girls are not clearly GH deficient (3), GH
administration accelerates growth in a dose-dependent way (4, 5, 6). In
addition, recent reports reported a considerable increase in adult
height in girls who started GH treatment at a relatively young age
(7, 8, 9).
The general clinical impression of body proportions of untreated girls
with TS is that these girls have a more coarse and stocky figure
compared to healthy girls. This is confirmed by earlier studies
describing relatively short lower extremities and relatively broad
shoulders and pelvis (10, 11, 12). Little is known about the effects of
supraphysiological GH dosages given for a long time during childhood.
The most remarkable reported changes in body proportions in TS after 2
yr of GH treatment were an increase in pelvic width and an increased
length and breadth of hands and feet compared to the increase in height
(10, 13). Four-year data on height and sitting height (SH) were
described by Rongen et al., demonstrating no change in
proportion (14).
To determine the body proportions before, during, and after long term
GH treatment, we measured height, SH, hand length (Hand), foot length
(Foot), biacromial diameter (Biac), and biiliacal diameter (Biil) in 68
girls with TS participating in a randomized dose-response study. The
effect on height was described previously (15). We now report body
proportions during childhood, comparing 7-yr data from 3 GH dosage
groups. Data from all girls who have reached adult height have been
evaluated as well.
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Subjects and Methods
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Sixty-eight previously untreated girls with TS were enrolled in
a multicenter GH dose-response study. The diagnosis was confirmed by
lymphocyte chromosomal analysis. Inclusion criteria were a
chronological age between 2–11 yr, height below the 50th percentile
for healthy Dutch girls (16), and normal thyroid function. Exclusion
criteria were associated endocrine and/or metabolic disorders, growth
failure caused by other disorders or emotional deprivation,
hydrocephalus, previous use of drugs that could interfere with GH
treatment, and spontaneous puberty (17). Written informed consent was
obtained from the girls and their parents or custodians. The study
protocol was approved by the ethics committee of each participating
center.
Sixty-eight girls were approached, and after the randomization all
girls started GH treatment. After stratification for chronological age
and height SD score for chronological age girls were
randomly assigned to the following groups: group A (n = 23),
receiving 4 IU/m2 body surface·day (equivalent
to 0.045 mg/kg); group B (n = 23), receiving 4
IU/m2·day in the first year, followed by 6
IU/m2·day; and group C (n = 22), receiving
4 IU/m2·day in the first year, 6
IU/m2·day in the second year, and thereafter 8
IU/m2·day.
Biosynthetic human GH (Norditropin, Novo Nordisk A/S,
Bagsvaerd, Denmark) was given sc once daily at bedtime using a pen
injection system. Every 3 months the total GH dose was adjusted to the
calculated body surface. According to study protocol, treatment was
stopped when subjects had grown less than 1 cm over 6 months. After the
first 4 yr of the study period, girls started estrogen therapy when
they had reached the age of 12 yr. In the first 2 yr of estrogen
therapy, the girls received 5 µg 17ß-estradiol/kg BW·day, in the
third year they received 7.5 µg/kg·day, and thereafter they were
given 10 µg/kg·day.
Height, SH, Hand (left), Foot (left), Biac, and Biil were measured at
baseline and subsequently every 6 months by two trained observers.
Measurements were taken according to the procedure of Cameron (18).
Height and SH were obtained using a Harpenden stadiometer and SH table.
The other measurements were taken with the Harpenden anthropometer. Two
measurements per visit were made, and the mean was used for the
analysis. The results of each measurement were adjusted for age and sex
and expressed as a SD score. When GH treatment was stopped,
the last available measurements at discontinuation of GH treatment were
considered the definite values, assuming that no change in body
proportions will take place after stopping GH treatment. For the
evaluation of body proportions in the girls after reaching adult
height, the reference values at the age of 18 yr were used for
calculating the SD scores. The data of the Oosterwolde
Study were used as references for healthy Dutch girls (19). This
reference population consisted of 1093 Dutch girls, ranging from birth
to 18 yr of age. To calculate SD scores, data from the
reference population were transformed using the LMS method (20, 21).
This method transforms the reference data at each age to a normal
distribution. In addition, the SD scores of the
measurements of SH, Hand, Foot, Biac, and Biil were adjusted for the
height SD score and expressed as the shape value. The shape
value, in this example defined as the SH SD score adjusted
for the height SD score, was calculated using the formula
(10, 22): shape SH = (SH SD score - height
SD score)/(2 - 2r), in which r is the correlation
coefficient between height and SH in the reference population. Values
less than -2 or more than +2 were considered outside the normal
range.
Unfortunately, no reference values from untreated girls with TS were
available, except for height (Dutch-Swedish-Danish Turner references)
(2) and SH (Dutch Turner references) (12). Because the reference
populations for height and SH were not totally identical, and the
correlation coefficient between height and SH in girls with TS was not
known, only SD scores of both measurements were calculated
using the reported means and SDS per yr. For the evaluation
of body proportions in the girls after reaching adult height, the
Turner reference values at maximum ages of 21 and 23 yr were used for
calculating the Turner SD scores of height and SH,
respectively. Seven girls were of non-Caucasian origin (3 in group A, 3
in group B, and 1 in group C). Although reference values for body
proportions of non-Caucasian girls might be somewhat different compared
to our Caucasian references, all girls were included in the statistical
analysis. Pubertal stages were assessed according to the method of
Tanner (17).
Results are expressed as the mean (SD), unless indicated
otherwise. At baseline, after 7 yr, and after reaching adult height,
SD scores and shape values were compared with zero using
Student’s one-sample t tests. SD
scores or shape values after 7 yr of GH treatment or after reaching
adult height were compared to baseline using paired Student’s
t tests. Differences in change in shape values between the
GH dosage groups were first tested by a linear trend test to assess a
possible dose-dependent effect. In case of a significant result, this
was followed by comparisons with Student’s two-sample t
tests. An intention to treat analysis was performed based on all
available data. P < 0.05 was considered
significant.
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Results
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The trial started in 1989. In October of 1997, all girls had been
followed for 7 yr. At the end of August 1998, 32 patients had
discontinued GH treatment. In each group 1girl dropped out of the study
long before reaching adult height for the following reasons:
noncompliance, presumed increase in muscle mass and decline in school
performance, and desire to initiate estrogen therapy before the fourth
year of GH treatment. In another girl in group B no measurements of
body proportions were available after 4 yr of treatment. Therefore,
analysis of body proportions during long term GH treatment was not
possible in these four girls. Table 1
lists the baseline clinical data of the remaining 64 girls as well as
those of the 32 girls who had discontinued GH treatment after reaching
(near) adult height. The 3 groups of patients had similar initial
characteristics.
7-yr evaluation
Figure 1 shows the SD
scores of the measurements at baseline and during 7 yr of GH treatment
in groups A, B, and C, respectively. At the start of GH treatment, all
mean SD scores were significantly lower than zero,
indicating stunted growth in several body parts. However, the baseline
SD score of height was lower than the SD scores
of the other measurements. After 7 yr of GH treatment all
SD scores had increased significantly compared to baseline.
The SD scores of height, SH, Biac, and Biil showed an
increase, especially in the first 4 yr of treatment, whereas the
SD scores of Hand and Foot demonstrated a sustained
increase throughout the entire study period up to values higher than
zero in the higher GH dosage groups.
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Figure 1. Mean (SD) SD scores
using reference values from healthy Dutch girls at baseline and during
7 yr of GH treatment in groups A (black bars), B
(gray bars), and C (white
bars), respectively. Significant differences from zero
(1, P < 0.001; 2, P < 0.005;
3, P < 0.05) and significant changes from baseline
to 7 yr of GH treatment (a, P < 0.001) are
indicated.
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The SD scores of height and SH using the Turner references
are presented in Fig. 2. At the start of
treatment, height and SH were not different from those in Turner
controls, except for SH in group B. After 7 yr, height and SH showed
similar increases, suggesting no obvious change in body proportion
between height and SH.
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Figure 2. Mean (SD) SD scores
of height and SH using the Turner references at baseline and during 7
yr of GH treatment in groups A (black bars), B
(gray bars), and C (white bars),
respectively. Significant differences from zero (1,
P < 0.001) and significant changes from baseline
to 7 yr of GH treatment (a, P < 0.001) are
indicated.
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Figure 3 shows the shape values at
baseline and during 7 yr of treatment for groups A, B, and C. At the
start of the treatment all mean shape values were significantly higher
than zero, indicating a relatively large trunk, relatively large hands
and feet, and relatively broad shoulders and pelvis compared to height.
However, most shape values were within the normal range. The shape
values of SH and Biac had not significantly changed over the 7 yr,
whereas the shape value of Biil had significantly decreased. The mean
shape values of Hand showed a decrease in the first years of the study
followed by an increase up to values around +2; however, they were only
statistically significant from baseline in group C. The shape values of
Foot increased significantly during treatment up to values +2 or
greater in all three GH dosage groups. Only the increase in shape value
of Foot was significantly higher in groups B and C compared to that in
group A, without a significant difference between groups B and C.
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Figure 3. Mean (SD) shape values at
baseline and during 7 yr of treatment for groups A (black
bars), B (gray bars), and C (white
bars), respectively. Significantly differences from zero (1,
P < 0.001; 2, P < 0.005) and
significant changes from baseline to 7 yr of GH treatment (a,
P < 0.001; b, P < 0.005; c,
P < 0.05) are indicated. Significant differences
in the changes in shape value from baseline to 7 yr of GH treatment in
this GH dosage group compared to group A were also indicated (*,
P < 0.05; **, P < 0.005).
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Girls who remained prepubertal throughout the entire study period
(n = 24) showed similar patterns in shape values as the whole
study group (data not shown).
Body proportions after reaching adult height
Thirty-two patients (groups A, B, and C; n = 10, 10, and 12,
respectively) have discontinued GH treatment after a mean duration of
treatment of 7.3 yr (1.1) (range, 5.0–8.5 yr). Twenty girls had
discontinued GH treatment because of a height velocity less than 1 cm
over 6 months, and 12 girls stopped GH treatment in the last phase of
growth because they were satisfied with their attained height.
The baseline clinical data of these 32 girls were, except for age,
comparable with the baseline data of the total group of 64 girls (Table 1
). At the last measurements, the mean (SD) age was 15.6
(0.7) yr in group A, 15.2 (1.3) yr in group B, and 15.2 (0.9) yr in
group C. Although, the duration of the GH treatment (from baseline to
the last measurement) seemed to be shorter in groups B [6.7 (1.3)]
and C [7.1 (1.2)] than in group A [7.6 (0.7)], the linear trend
test showed no significant dose-dependent effect.
Table 2 shows the SD scores
and shape values at the start of treatment and at discontinuation of GH
treatment. Baseline values of these 32 girls were similar to those of
the total group of 64 girls. Except for the SD score of SH
in group A, all SD scores had significantly increased
compared to baseline. The largest increase in SD scores was
seen in Hand and Foot. In group C, Foot had increased to a mean value
significantly higher than that in healthy women. The shape values of
Biac and Biil showed no change compared to baseline, whereas the shape
value of SH had significantly decreased. The decrease in the shape
value of SH was significant less in groups B and C than in group A. The
mean shape values of Hand deviated more toward abnormal high values;
however, these changes were not statistically significant. The shape
value of Foot had increased significantly to values outside the normal
range, without significant differences between the GH dosage
groups.
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Table 2. Mean (SD) SD scores and
shape values at baseline and after reaching adult height in 32 girls
who have reached adult height
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The SD scores of height using the Turner references had
significantly increased by 1.7 (0.5) in group A, 1.9 (0.6) in group B,
and 2.2 (0.7) in group C compared to baseline (P <
0.001). The increase in the SD score of SH using
Turner references increased by 0.6 (0.5) in group A, 0.9 (0.4) in group
B, and 1.3 (0.7) in group C compared to baseline (P =
0.004 for group A; P < 0.001 for groups B and C).
Thus, the increase in the Turner SD score for
height seems to be higher than that in the SD
score for SH.
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Discussion
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The present study showed that untreated girls with TS, between
2–11 yr of age, are short and have smaller hands and feet and narrow
shoulders and pelvis compared to healthy peers. As height is more
affected than other parts of the body, untreated girls have, on the
average, a relatively large trunk, relatively large hands and feet, and
relatively broad shoulders and pelvis compared to height. Most shape
values, however, were within the normal range. Our data are in line
with the results reported by Gerver et al., describing
higher mean shape values in somewhat older girls (6–19 yr) with TS
(10). Zellner et al. demonstrated higher
SD scores of Hand and Foot than of height,
indicating relatively large hands and feet (13). Rongen et
al. reported that especially younger girls with TS have relatively
short legs compared to trunk height (12).
During GH treatment all measured parts of the body increased in size to
values close to those in healthy peers or even higher. The 7-yr data
showed that the increase in SH and Biac was comparable with that in
height, resulting in no change in shape values. Although we do not have
shape values for SH based on Turner references, our 7-yr Turner
SD scores also suggest no change in the proportion of SH to
height. The shape value of the Biil had decreased during the 7 yr to
values more appropriate for height. Hand and Foot showed a sustained
increase in size throughout the entire study period, resulting in mean
SD scores above zero and shape values approximately +2 or
higher. Only the increase in the shape value of Foot was dose
dependent. Other studies in girls with TS also reported a higher
increase in the SD scores of hand and foot than in that of
height after 2 yr of GH treatment (10, 13). Rongen et al.
demonstrated, as we did, no change in the preexisting disproportion
between height and SH during childhood after 4 ys of GH treatment (14).
However, the biggest change in body proportions in the study of Gerver
et al. was the increased Biil compared to height after 2 yr
of GH treatment (10). In our study, the shape value of Biil decreased
during 7 yr of GH treatment and was not changed in the subgroup of
girls who had reached adult height. The discrepancy between the
previously published data and our data concerning Biil compared to
height may be caused by the good catch-up in height and the lesser
increase in Biil. Compared to the other measurements, the measurement
of Biil is higher influenced by the increase in body fat, which is seen
especially in adolescents and adults with TS.
Thirty-two girls had reached their adult stature after long term GH
treatment. For the present study, we made the assumption that no change
in body proportions will take place after stopping GH treatment. Our
clinical impression is that only some additional millimeters to a
centimeter in height can be achieved in the years after discontinuation
of treatment after reaching (near) final height. However, we assumed
that the possible additional millimeters in height will be accompanied
by a similar increase in size of other parts of the body after stopping
GH treatment. Preliminary data for older girls with TS obtained by our
group seem to confirm this assumption; however, follow-up of the girls
in the present study is required to substantiate this. The data from
the 32 girls showed no change in shape values of Biac and Biil.
Although the shape value of Hand had deviated more from normal compared
to baseline, the change was not significant. In contrast, Foot had
increased to mean values equal to or higher than the mean value for
healthy women and shape values outside the normal range. However, no
significant differences between the GH dosage groups were found. The
shape value of SH showed a decrease to values close to zero, especially
in group A. The SD scores for height and SH using Turner
references showed the same pattern: a higher increase in height than in
SH. Thus, in the girls who had reached adult height after long term GH
treatment, the disproportion between SH and height had improved, but
the proportion of Foot to height had worsened.
The cause and mechanism of the change in body proportions after long
term GH treatment in girls with TS are not clear-cut. In our study,
girls in group A received the usual GH dose, but higher GH doses were
given in groups B and C. The 7-yr increase in shape value of Foot was
dose dependent, suggesting a GH-induced abnormality. In adults,
excessive GH secretion can lead to acromegalic features, including big
hands and feet, which are caused by thickening of the bone and
surrounding soft tissue. Less is known about the effects of high GH
levels during childhood. Although we did not include systematic
radiographic measurements of bone length and soft tissue in our study,
we saw no obvious soft tissue thickening on the standardized x-rays of
the hand. This suggests that in girls with TS the increase in the size
of the hands is caused by longitudinal growth of bone and does not seem
to be part of the acromegalic changes. In addition, it has been
reported that high GH levels in children during the growth phase
(gigantism; most common cause is an autonomously functioning pituitary
adenoma) result in proportional growth in length and width of the bones
(23). As in most other studies, we did not include a randomized control
group receiving no GH treatment until adult height. Unfortunately, no
reference values for TS were available for Hand, Foot, Biac, and Biil
during the growth phase. Therefore, we do not know the natural
development of those body proportions in untreated girls with TS during
childhood. However, recent reference values were reported for adult
women with TS, who had received no GH therapy in childhood (24). To
compare those data with ours, we calculated the mean shape values from
the SD scores of that study, because the same reference
population was used as in our study. It was shown that untreated adult
women with TS have no disproportion between height and SH, but shape
values of Hand were even higher than those in our 32 girls who had
reached adult height. The mean shape value of Foot in these women was
as high as that in group A, but was lower than those in groups B and C
in our analysis of adult data. The shape values for Biac and Biil were
considerably higher than our adult shape values. These reference data
suggest that the decrease in shape SH and the increase in shape values
for Hand and Feet found in our study are partly due to the natural
development of these body proportions in girls with TS. As observed in
forms of skeletal dysplasia, body proportions may change during
childhood. One might speculate that GH exaggerates this naturally
occurring disproportionate growth in girls with TS while they reach
a normal height. Remarkably, our data from a different patient
group receiving 6 IU GH/m2·day showed no
abnormal growth of hands and feet (Sas, T. C., W. J. Gerver, R. de
Bruin, et al., submitted for publication). Because the
increments in shape values of Hand and Foot appeared mainly after the
fourth year, estrogen therapy was thought to be one of the causes of
the abnormal development of Hand and Foot. However, the same pattern
was seen in the girls without pubertal signs and estrogen therapy
throughout the study. Therefore, the changes in body proportions could
not be attributed to puberty or estrogen therapy.
As described in previous reports, long term GH treatment results in a
height within the normal range in most girls with TS (7, 15). In the
present study we showed that the increase in height is accompanied by
abnormal growth of the feet, resulting in relatively large feet for
height as well as for age. Especially in the last phase of growth, some
girls in our study complained about big feet. The possibility of
additional foot growth may have influenced their decision to
discontinue GH treatment before adult height was reached.
In conclusion, girls with TS have, on the average, a relatively large
trunk, hands, and feet, and broad shoulders and pelvis compared to
height. The increase in height after long term GH treatment is
accompanied by an even greater increase in the size of the feet and a
moderate improvement of the disproportion between height and SH. Recent
published reference data for adults with TS and results of a different
GH-treated patient group suggest that the disproportionate growth of
feet is part of the natural development in TS, but might be influenced
by higher GH dosages.
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Acknowledgments
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Mrs. Ingrid van Slobbe, research -nurse, is gratefully
acknowledged for her assistance.
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Footnotes
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1 This work was supported by Novo Nordisk A/S (Bagsvaerd,
Denmark). 
Received July 14, 1999.
Revised September 17, 1999.
Accepted September 20, 1999.
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References
|
|---|
-
Ranke MB, Pflüger H, Rosendahl W, et al. 1983 Turner syndrome: spontaneous growth in 150 cases and review of the
literature. Eur J Pediatr. 141:81–88.[CrossRef][Medline]
-
Karlberg J, Albertsson-Wikland K, Naeraa RW,
Rongen-Westerlaken C, Wit JM. 1993 Reference values for
spontaneous growth in Turner girls and its use in estimating treatment
effects. In: Hibi I, Takano K, eds. Basic and clinical approach to
Turner syndrome. Amsterdam: Elsevier Science; 83–92.
-
Wit JM, Massarano AA, Kamp GA, et al. 1992 Growth
hormone (GH) secretion in Turner girls as determined by time series
analysis. Acta Endocrinol (Copenh). 127:7–12.[Medline]
-
Stahnke N, Stubbe P, Attanasio A, Reinhardt D, Partsch
CJ, Sippell WG. 1993 GH therapy alone or together with oxandrolone
in 212 patients with Turner syndrome (TS): the German experience. In:
Hibi I, Takano K, eds. Basic and clinical approach to Turner syndrome,
Amsterdam: Elsevier Science; 315–322.
-
Teunenbroek van A, Muinck Keizer-Schrama de SMPF,
Stijnen T, et al. 1996 Yearly stepwise increments of the growth
hormone dose results in a better growth response after four years in
girls with Turner syndrome. J Clin Endocrinol Metab. 81:4013–4021.[Abstract/Free Full Text]
-
Carel JC, Mathivon L, Gendrel C, Ducret JP, Chaussain
JL. 1998 Near normalization of final height with adapted doses of
growth hormone in Turner’s syndrome. J Clin Endocrinol Metab. 83:1462–1466.[Abstract/Free Full Text]
-
Rosenfeld RG, Attie KM, Frane J, et al. 1998 Growth hormone therapy of Turner’s syndrome: Beneficial effect on
adult height. J Pediatr. 132:319–324.[CrossRef][Medline]
-
Haeusler G, Schmitt K, Blümel P, Plöchl E,
Waldhör T, Frisch H. 1996 Growth hormone in combination with
anabolic steroids in patients with Turner syndrome: effect on bone
maturation and final height. Acta Paediatr. 85:1408–1414.[Medline]
-
Nilsson KO, Albertsson-Wikland K, Alm J, et al. 1996 Improved final height in girls with Turner’s syndrome treated
with growth hormone and oxandrolone. J Clin Endocrinol Metab. 81:635–40.[Abstract]
-
Gerver WJM, Drayer NM, van Es A. 1992 Does growth
hormone treatment of patients with Turner’s syndrome cause an abnormal
body shape? Acta Paediatr. 81:691–694.[Medline]
-
Neufeld ND, Lippe BM, Kaplan SA. 1978 Disproportionate growth of the lower extremities. Am J Dis Child. 132:296–298.[Abstract]
-
Rongen-Westerlaken C, Rikken B, Vastrick P. 1993 Body proportions in individuals with Turner syndrome. Eur J
Pediatr. 152:813–817.[Medline]
-
Zellner K, Keller E, Kromeyer K, Jaeger U. 1997 Acromegaloidal changes in Ullrich-Turner syndrome after treatment with
growth hormone. Acta Med Auxol. 29:125- 133.
-
Rongen-Westerlaken C, Nienhuis HE, Wit JM, et al. 1993 The effect of four years of growth hormone therapy on body stature
and proportions in patients with Turner syndrome. In: Hibi I, Takano K,
eds. Basic and clinical approach to Turner syndrome. Amsterdam:
Elsevier Science; 83–92.
-
Sas TC, Muinck Keizer-Schrama de SMPF, Stijnen T, et
al. Normalization of height in girls with Turner’s syndrome after
long-term growth hormone treatment: results of a randomized
dose-response trial. In press.
-
Roede MJ, Wieringen JC. 1985 Growth diagrams 1980.
Netherlands third nationwide survey. Tijdschr Soc Gezondh.
63(Suppl):1–34.
-
Tanner JM, Whitehouse R. 1976 Clinical longitudinal
standards for height, weight, height velocity, weight velocity and
stages of puberty. Arch Dis Child. 51:170–179.[Abstract]
-
Cameron N. 1987 The methods of auxological
anthropometry. In: Falkner F, Tanner JM eds. Human growth, vol 2.
London: Tindall.
-
Gerver WJM, de Bruin R. 1996 Paediatric
morphometrics, a reference manual. Utrecht: Bunge.
-
Cole TJ. 1989 The British, American NCHS, and Dutch
weight standards compared using the LMS method. Am J Hum Biol. 1:397–408.[CrossRef]
-
Cole TJ. 1989 Using the LMS method to measure
skewness in the NCHS and Dutch National height standards. Ann Hum Biol. 16:407–419.[CrossRef][Medline]
-
Tanner JM. 1952 The assessment of growth and
development in children. Arch Dis Child. 27:10–33.
-
Chew FS. 1991 Radiologic manifestations in the
musculoskeletal system of miscellaneous endocrine disorders. Radiol
Clin North Am. 29:135–147.[Medline]
-
Gravholt CH, Naeraa RW. 1997 Reference values for
body proportions and body composition in adult women with
Ullrich-Turner syndrome. Am J Med Genet. 72:403- 408.[CrossRef][Medline]
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Abstract
Introduction
