3 research outputs found
Added Centimetres and Their Repercussions: How effective and safe is growth hormone in the treatment of short stature in girls with Turner syndrome and in children born small for gestational age?
The most common clinical characteristic of Turner syndrome (TS) is short
stature. Although girls with TS are not growth hormone (GH) deficient,
studies show that long-term GH treatment in TS leads to normalisation of
height during childhood. In this chapter the results and conclusions are
summarised of the multi-centre randomised dose-response growth hormone
(GH) trial evaluating the efficacy, safety and psychosocial effect of long-term
GH treatment on girls with TS. The TS trial was an open trial consisting of 68
untreated girls, aged between 2 and 11 years, with TS. The girls were
randomly assigned to a group using 4 IU GH/m2/day, to a group using 4 IU
GH/m2/day in the first year, and 6 IU GH/m2/day in the years thereafter, or
to a group using 4 IU GH/m2/day in the first, 6 IU GH/m2/day in the second,
and 8 IU GH/m2/day in the years thereafter (~ 0.045, 0.067, or 0.090
mg/kg/day). After at least 4 years of GH treatment, at a minimum age of 12
years, a low dose of micronised oestradiol was given to induce puberty
Effect of discontinuation of long-term growth hormone treatment on carbohydrate metabolism and risk factors for cardiovascular disease in girls with Turner syndrome
GH treatment increases insulin levels in girls with Turner syndrome (TS),
who are already predisposed to develop diabetes mellitus and other risk
factors for developing cardiovascular disease. Therefore, in the present
study, we investigated carbohydrate metabolism and several other risk
factors that may predict development of cardiovascular disease in girls
with TS after discontinuation of long-term GH treatment. Fifty-six girls,
participating in a randomized dose-response study, were examined before,
during, and 6 months after discontinuing long-term GH treatment with doses
of 4 IU/m(2).d ( approximately 0.045 mg/kg.d), 6 IU/m(2).d, or 8
IU/m(2).d. After a minimum of 4 yr of GH treatment, low-dose micronized
17beta-estradiol was given orally. Mean (SD) age at 6 months after
discontinuation of GH treatment was 15.8 (0.9) yr. Mean duration of GH
treatment was 8.8 (1.7) yr. Six months after discontinuation of GH
treatment, fasting glucose levels decreased and returned to pretreatment
levels. The area under the curve for glucose decreased to levels even
lower than pretreatment level (P < 0.001). Fasting insulin levels and the
area under the curve for insulin decreased to levels just above
pretreatment level (P < 0.001 for both), although being not significantly
different from the control group. No dose-dependent differences among GH
dosage groups were found. At 6 months after discontinuation, impaired
glucose tolerance was present in 1 of 53 girls (2%), and none of the girls
developed diabetes mellitus type 1 or 2. Compared with pretreatment, the
body mass index SD-score had increased (P < 0.001), and the systolic and
diastolic blood pressure SD-score had decreased significantly at 6 months
after discontinuation of GH treatment (P < 0.001 for both) although
remaining above zero (P < 0.001, P < 0.05, and P < 0.005, respectively).
Compared with pretreatment, total cholesterol (TC) did not change after
discontinuation of GH treatment, whereas the atherogenic index [AI =
TC/high-density lipoprotein cholesterol (TC/HDL-c)] and low-density
lipoprotein cholesterol (LDL-c) had decreased; and both HDL-c and
triglyceride levels increased (P < 0.001 for AI, LDL-c, and HDL-c; P <
0.05 for triglyceride). Compared with the control group, AI, serum TC, and
LDL-c levels were significantly lower (P < 0.001 for all), whereas HDL-c
levels were significantly higher (P < 0.05). In conclusion, after
discontinuation of long-term GH treatment in girls with TS, the GH-induced
insulin resistance disappeared, blood pressure decreased but remained
higher than in the normal population, and lipid levels and the AI changed
to more cardio-protective values
Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens
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