T. Vulsma
http://repub.eur.nl/ppl/2417/
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RePub, Erasmus University RepositoryFinal height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens
http://repub.eur.nl/pub/10108/
Wed, 01 Jan 2003 00:00:01 GMT<div>Y.K. van Pareren</div><div>H.M. Reeser</div><div>S.M.P.F. de Muinck Keizer-Schrama</div><div>Th. Stijnen</div><div>T.C.J. Sas</div><div>S.L.S. Drop</div><div>M. Jansen</div><div>B.J. Otten</div><div>J.J. Hoorweg-Nijman</div><div>C. Rongen-Westerlaken</div><div>T. Vulsma</div><div>W.H. Stokvis-Brantsma</div><div>J.J. Gosen</div><div>C.W. Rouwé</div><div>W.J. Gerver</div>
Although GH treatment for short stature in Turner syndrome is an accepted
treatment in many countries, which GH dosage to use and which age to start
puberty induction are issues of debate. This study shows final height (FH)
in 60 girls with Turner syndrome treated in a randomized dose-response
trial, combining GH treatment with low dose estrogens at a relatively
young age. Girls were randomly assigned to group A (4 IU/m(2).d;
approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter
6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6
IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH
treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized
17beta-estradiol was given orally. After a mean duration of GH treatment
of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH,
expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in
group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or
-0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected
for height SD score and age at start of treatment, was significant between
groups A and B [regression coefficient, 4.1; 95% confidence interval (CI),
1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3,
7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI,
-1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD
score, more than -2). After starting estrogen treatment, the decrease in
height velocity (HV) changed significantly to a stable HV, without
affecting bone maturation (change in bone age/change in chronological
age). The following variables contributed significantly to predicting FH
SD score: GH dose, height SD score (ref. normal girls), chronological age
at start of treatment, and HV in the first year of GH treatment. GH
treatment was well tolerated. In conclusion, GH treatment leads to a
normalization of FH in most girls, even when puberty is induced at a
normal pubertal age. The optimal GH dosage depends on height and age at
the start of treatment and first year HV.Final height in girls with Turner's syndrome treated with once or twice daily growth hormone injections. Dutch Advisory Group on Growth Hormone
http://repub.eur.nl/pub/9094/
Fri, 01 Jan 1999 00:00:01 GMT<div>T.C.J. Sas</div><div>T. Vulsma</div><div>W.J. Gerver</div><div>S.L.S. Drop</div><div>H.M. Reeser</div><div>M. Jansen</div><div>S.M.P.F. de Muinck Keizer-Schrama</div><div>Th. Stijnen</div><div>A. van Teunenbroek</div><div>A.C.S. Hokken-Koelega</div><div>J.J.J. Waelkens</div><div>G.G. Massa</div><div>H.A. Delemarre-van de Waal</div>
OBJECTIVES: To study final height in girls with Turner's syndrome treated
with once or twice daily injections of growth hormone (GH) in combination
with low dose ethinyl oestradiol. DESIGN: Until final height was reached,
the effect of fractionated subcutaneous injections given twice daily was
compared with once daily injections of a total GH dose of 6 IU/m2/day.
Twice daily injections were given as one third in the morning and two
thirds at bedtime. All girls concurrently received low dose oestradiol
(0.05 microgram ethinyl oestradiol/kg/day, increased to 0.10
microgram/kg/day after 2.25 years). PATIENTS: Nineteen girls with Turner's
syndrome aged > or = 11 years (mean (SD) 13.6 (1.7) years). MEASUREMENTS:
To determine final height gain, we assessed the difference between the
attained final height and the final height predictions at the start of
treatment. These final height predictions were calculated using the
Bayley-Pinneau (BP) prediction method, the modified projected adult height
(mPAH), the modified index of potential height (mIPHRUS), and the Turner's
specific prediction method (PTSRUS). RESULTS: The gain in final height
(mean (SD)) was not significantly different between the once daily and the
twice daily regimens (7.6 (2.3) v 5.1 (3.2) cm). All girls exceeded their
adult height prediction (range, 1.6-12.3 cm). Thirteen of the 19 girls had
a final height gain > 5.0 cm. Mean (SD) attained final height was 155.5
(5.4) cm. A "younger bone age" at baseline and a higher increase in height
standard deviation score for chronological age (Dutch-Swedish-Danish
references) in the first year of GH treatment predicted a higher final
height gain after GH treatment. CONCLUSIONS: Division of the total daily
GH dose (6 IU/m2/day) into two thirds in the evening and one third in the
morning is not advantageous over the once daily GH regimen with respect to
final height gain. Treatment with a GH dose of 6 IU/m2/day in combination
with low dose oestrogens can result in a significant increase in adult
height in girls with Turner's syndrome, even if they start GH treatment at
a relatively late age.Normalization of height in girls with Turner syndrome after long-term growth hormone treatment: results of a randomized dose-response trial
http://repub.eur.nl/pub/9212/
Fri, 01 Jan 1999 00:00:01 GMT<div>T.C.J. Sas</div><div>B.J. Otten</div><div>J.J. Hoorweg-Nijman</div><div>T. Vulsma</div><div>S.L.S. Drop</div><div>G.G. Massa</div><div>C.W. Rouwé</div><div>C. Rongen-Westerlaken</div><div>H.M. Reeser</div><div>J.J. Gosen</div><div>W.J. Gerver</div><div>S.M.P.F. de Muinck Keizer-Schrama</div><div>Th. Stijnen</div><div>M. Jansen</div>
Short stature and ovarian failure are the main features in Turner syndrome
(TS). To optimize GH and estrogen treatment, we studied 68 previously
untreated girls with TS, age 2-11 yr, who were randomly assigned to one of
three GH dosage groups: group A, 4 IU/m2 day (approximately 0.045 mg/kg x
day); group B, first yr 4, thereafter 6 IU/m2 x day (approximately 0.0675
mg/kg/day); group C, first yr 4, second yr 6, thereafter 8 IU/m2 x day
(approximately 0.090 mg/kg x day). In the first 4 yr of GH treatment, no
estrogens for pubertal induction were given to the girls. Thereafter,
girls started with 17beta-estradiol (5 microg/kg bw x day, orally) when
they had reached the age of 12 yr. Subjects were followed up until
attainment of adult height or until cessation of treatment because of
satisfaction with the height achieved. Seven-year data of all girls were
evaluated to compare the growth-promoting effects of three GH dosages
during childhood. After 7 yr, 85% of the girls had reached a height within
the normal range for healthy Dutch girls. The 7-yr increment in height
SD-score was significantly higher in groups B and C than in group A. In
addition, we evaluated the data of 32 of the 68 girls who had completed
the trial after a mean duration of treatment of 7.3 yr (range, 5.0 -
8.75). Mean (SD) height was 158.8 cm (7.1), 161.0 cm (6.8), and 162.3 cm
(6.1) in groups A, B, and C, respectively. The mean (SD) difference
between predicted adult height before treatment and achieved height was
12.5 cm (2.1), 14.5 cm (4.0), and 16.0 cm (4.1) for groups A, B, and C,
respectively, being significantly different between group A and group C.
GH treatment was well tolerated in all three GH dosage groups. In
conclusion, GH treatment starting in relatively young girls with TS
results in normalization of height during childhood, as well as of adult
height, in most of the individuals. With this GH and estrogen treatment
regimen, most girls with TS can grow and develop much more in conformity
with their healthy peers.