176 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
Vreemde ogen dwingen niet altijd
Je zou op basis van het algemene principe "vreemde ogen dwingen" verwachten dat accountantscontrole leidt tot getrouwe jaarrekeningen. Wat betreft accountantscontrole geldt echter dat het begrip "vreemde ogen" meerdere facetten omvat, en daarom genuanceerd moet worden bezien. In dit artikel onderzoeken wij de invloed van de onafhankelijkheid van één paar vreemde ogen (variërend in mate van onafhankelijkheid/vreemdheid) en de invloed van twee paar ogen (joint audit) op de continuïteitsinschatting. Uit dit onderzoek blijkt dat – vreemd genoeg – bij vreemdere ogen (ten gevolge van verlaagde non-audit dienstverlening en joint audit) juist minder continuïteitsparagrafen worden afgegeven. De uitkomsten geven – voor regelgevende instanties – aanleiding om nader onderzoek hiernaar te doen
Puberty in growth hormone-treated children born small for gestational age (SGA)
Seventy-five small for gestational age (SGA) children were studied in a
randomized, double-blind, dose-response GH trial with either 1 or 2 mg
GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data
were compared with Dutch reference data. In SGA boys, mean (SD) age at
onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was
10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d,
respectively. SGA boys treated with the lower GH dose started puberty
later than the appropriate for gestational age (AGA) controls; for the
other GH-dosage groups there was no significant difference in age at onset
of puberty compared to AGA controls. The age at menarche and the interval
between breast stage M2 and menarche were not significantly different for
GH-treated SGA girls compared to their peers. The duration of puberty and
pubertal height gain of GH-treated SGA boys and girls were not
significantly different between the two GH-dosage groups and were
comparable with untreated short children born SGA. In conclusion,
long-term GH therapy in short SGA children has no influence on the age at
onset and progression of puberty compared to AGA controls, regardless of
treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and
pubertal height gain were not significantly different between the
GH-dosage groups
Psychosocial functioning after discontinuation of long-term growth hormone treatment in girls with Turner syndrome
Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestational age.
Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestational age
Hyperlipidemia, diabetes mellitus type 2, and coronary heart disease have
been associated with being born small for gestational age (SGA). It has
been reported that GH treatment induced higher insulin levels, which has
led to concern regarding the long-term effect of GH treatment in
predisposed individuals such as children born SGA. In this study, we
assessed the effect of discontinuation of long-term GH treatment in 47
adolescents born SGA on oral glucose tolerance tests, blood pressure (BP),
and serum lipid levels for two GH dosage groups (3 vs. 6 IU/m2 x d). At 6
months after discontinuation of GH treatment mean (SD) age was 16.0 (2.1)
yr. Mean duration of GH treatment had been 6.9 (1.5) yr. Fasting glucose
levels and 120-min area under the curve for glucose 6 months after
discontinuation of GH treatment showed no difference from pretreatment
levels for both GH dosage groups. After discontinuation of GH treatment,
fasting insulin levels returned to pretreatment levels (8.4 mU/liter),
whereas the 120-min area under the curve for insulin decreased, compared
with 6-yr levels (P < 0.01), regardless of GH dosage group. No significant
difference was found when levels were compared with a control group. In
addition, for both GH dosage groups, no significant changes in systolic
and diastolic BP SD score, total cholesterol, and atherogenic index (total
cholesterol/high-density lipoprotein cholesterol) were seen from 6 yr of
GH until 6 months after discontinuation of GH treatment. In conclusion, in
children born SGA, the GH-induced insulin insensitivity disappeared after
discontinuation of GH, even after long-term GH treatment. Furthermore, the
beneficial effect of GH on BP was not changed after discontinuation of GH,
and most children had normal lipid levels
Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial
The GH dose-response effect of long-term continuous GH treatment on adult
height (AH) was evaluated in 54 short children born small for gestational
age (SGA) who were participating in a randomized, double-blind,
dose-response trial. Patients were randomly and blindly assigned to
treatment with either 3 IU (group A) or 6 IU (group B) GH/m(2).d (
approximately 0.033 or 0.067 mg/kg.d, respectively). The mean (+/-SD)
birth length was -3.6 (1.4), the age at the start of the study was 8.1
(1.9) yr, and the height SD score (SDS) at the start of the study -3.0
(0.7). Seventeen of the 54 children were partially GH deficient
(stimulated GH peak, 10-20 mU/liter). Fifteen non-GH-treated,
non-GH-deficient, short children born SGA, with similar inclusion
criteria, served as controls [mean (+/-SD) birth length, -3.3 (1.2); age
at start, 7.8 (1.7) yr; height SDS at start, -2.6 (0.5)]. GH treatment
resulted in an AH above -2 SDS in 85% of the children after a mean (+/-SD)
GH treatment period of 7.8 (1.7) yr. The mean (SD) AH SDS was -1.1 (0.7)
for group A and -0.9 (0.8) for group B, resulting from a mean (+/-SD) gain
in height SDS of 1.8 (0.7) for group A and 2.1 (0.8) for group B. No
significant differences between groups A and B were found for AH SDS (mean
difference, 0.3 SDS; 95% confidence interval, -0.2, 0.6; P > 0.2) and gain
in height SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.1,
0.7; P > 0.1). When corrected for target height, the mean corrected AH SDS
was -0.2 (0.8) for group A and -0.4 (0.9) for group B. The mean (+/-SD) AH
SDS of the control group [-2.3 (0.7)] was significantly lower than that of
the GH-treated group (P < 0.001). Multiple regression analysis indicated
the following predictive variables for AH SDS: target height SDS, height
SDS, and chronological age minus bone age (years) at the start of the
study. GH dose had no significant effect. In conclusion, long-term
continuous GH treatment in short children born SGA without signs of
persistent catch-up growth leads to a normalization of AH, even with a GH
dose of 3 IU/m(2).d ( approximately 0.033 mg/kg.d)
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
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