10 research outputs found
Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency
To assess the effects of long-term continuous GH treatment on body
composition, blood pressure (BP), and lipid metabolism in children with
short stature born small for gestational age (SGA), body mass index (BMI),
skinfold thickness measurements, systemic BP measurements, and levels of
blood lipids were evaluated in 79 children with a baseline age of 3-11 yr
with short stature (height SD-score, < -1.88) born SGA (birth length
SD-score, < -1.88). Twenty-two of the 79 children were GH deficient (GHD).
All children participated in a randomized, double-blind, dose-response
multicenter GH trial. Four- and 6-yr data were compared between two GH
dosage groups (3 vs. 6 IU/m2 body surface/day). Untreated children with
short stature born SGA are lean (mean BMI SD-score, -1.3; mean SD-score
skinfolds, -0.8), have a higher systolic BP (SD-score, 0.7) but normal
diastolic BP (SD-score, -0.1), and normal lipids (total cholesterol, 4.7
mmol/L; low-density lipoprotein, 2.9 mmol/L; high-density lipoprotein, 1.3
mmol/L) compared with healthy peers. During long-term continuous GH
treatment, the BMI normalized without overall changes in sc fat compared
with age-matched references, whereas the BP SD-score and the atherogenic
index decreased significantly. Although the mean 6-yr increase in height
SD-score was significantly higher in the children receiving GH treatment
with 6 IU/m2 x day (2.7) than in those receiving treatment with 3 IU/m2
day (2.2), no differences in the changes in BMI, skinfold measurements,
BP, and lipids were found between the GH dosage groups. The pretreatment
SD-scores for BMI, skinfold, and BP, as well as the lipid levels, were not
significantly different between GHD and non-GHD children, but after 6 yr
of GH treatment the skinfold SD-score and BP SD-score had decreased
significantly more in the GHD than in the non-GHD children. Our data
indicate that GH treatment has at least up to 6 yr positive instead of
negative effects on body composition, BP, and lipid metabolism. In view of
the reported higher risk of cardiovascular diseases in later life in
children born SGA, further research into adulthood remains warranted
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
Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial
The growth-promoting effect of continuous GH treatment was evaluated over
5 yr in 79 children with short stature (height SD score, less than -1.88)
born small for gestational age (SGA; birth length SD score, less than
-1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage
groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an
exclusion criterium. After 5 yr of GH treatment almost every child had
reached a height well within the normal range for healthy Dutch children
and in the range of their target height SD score. Only in children who
remained prepubertal during the study period was the 5-yr increase in
height SD score (HSDS) for chronological age significantly higher in the
study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr
increment in HSDS for chronological age was not related to spontaneous GH
secretion, maximum GH levels after provocation, or baseline insulin-like
growth factor I levels. GH treatment was associated with an acceleration
of bone maturation regardless of the GH dose given. The HSDS for bone age
and predicted adult height increased significantly. GH treatment was well
tolerated. In conclusion, our 5-yr data show that long term continuous GH
treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA
results in a normalization of height during childhood followed by growth
along the target height percentile
Bone mineral density assessed by phalangeal radiographic absorptiometry before and during long-term growth hormone treatment in girls with Turner's syndrome participating in a randomized dose-response study
To assess bone mineral density (BMD) in girls with Turner's syndrome
before and during long-term treatment with GH, longitudinal measurements
using phalangeal radiographic absorptiometry were performed in 68 girls
with Turner's syndrome. These previously untreated girls, age 2-11 y,
participating in a randomized, dose-response trial, were randomly assigned
to one of three GH dosage groups: 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 (
approximately 0.0675 mg/kg/d); or group C, first year 4 IU/m(2)/d, second
year 6 IU/m(2)/d, thereafter 8 IU/m(2)/d ( approximately 0.090 mg/kg/d).
In the first 4 y of GH treatment, no estrogens for pubertal induction were
prescribed to the girls. Thereafter, girls started with 17beta-estradiol
(5 microg/kg body weight/d, orally) when they had reached the age of 12 y.
BMD results were adjusted for bone age and sex, and expressed as SD scores
using reference values of healthy Dutch girls. At baseline, almost every
individual BMD value of bone consisting predominantly of cortical bone, as
well as that of bone consisting predominantly of trabecular bone, was
within the normal range of healthy girls and the SD scores were not
significantly different from zero [mean (SE) 0.38 (0.22) and -0.04
(0.13)]. During 7 y of GH treatment, BMD SD scores showed a significant
increase to values significantly higher than zero [mean (SE) 0.87 (0.15)
and 0.95 (0.14)]. The increment in BMD SD score of bone consisting
predominantly of cortical bone was significantly higher in group C
compared with that of the other two GH dosage groups. The pretreatment
bone age was significantly negatively related to the increment in BMD SD
score. We found no significant influence of spontaneous puberty or the use
of low-dose estrogens in the last 3 y of the study period on the increment
in BMD SD score during 7 y of GH treatment. In conclusion, most untreated
young girls with Turner's syndrome have a normal volumetric BMD. During 7
y of GH treatment with 4, 6, or 8 IU/m(2)/d, the BMD SD score increased
significantly
Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children
Prenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is
associated with changes in the T-cell lymphocyte population in healthy
Dutch infants. We investigated whether these changes persist into later
childhood and whether background exposure to PCBs and dioxins is
associated with the prevalence of infectious or allergic diseases and
humoral immunity at preschool age. The total study group consisted of 207
healthy mother-infant pairs. We estimated prenatal exposure to PCBs and
dioxins by the sum of PCBs 118, 138, 153, and 180 (sigmaPCB) in maternal
and cord plasma and in breast-fed infants by the dioxin, planar, and
mono-ortho PCB toxic equivalent (TEQ) levels in human milk. At 42 months
of age, current body burden was estimated by the PCB in plasma. We
assessed the prevalence of infectious and allergic diseases by parent
questionnaire, and measured humoral immunity by antibody levels for mumps,
measles, and rubella after primary vaccination. We performed immunologic
marker analyses of lymphocytes in a subgroup of 85 children. Prenatal PCB
exposure was associated with an increased number of lymphocytes, T-cells,
and CD3CD8(+) (cytotoxic), CD4(+)CD45RO(+) (memory), T-cell receptor (TcR)
[alpha]ss(+), and CD3(+)HLA-DR(+) (activated) T cells and lower antibody
levels to mumps and measles at preschool age. Adjusted for confounders,
prenatal PCB exposure was associated with less shortness of breath with
wheeze, and current PCB body burden was associated with a higher
prevalence of recurrent middle-ear infections and of chicken pox and a
lower prevalence of allergic reactions. A higher dioxin TEQ was associated
with a higher prevalence of coughing, chest congestion, and phlegm. We
conclude that in Dutch preschool children the effects of perinatal
background exposure to PCBs and dioxins persist into childhood and might
be associated with a greater susceptibility to infectious diseases. Common
infections acquired early in life may prevent the development of allergy,
so PCB exposure might be associated with a lower prevalence of allergic
diseases
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
Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations
Context: Most girls with Turner syndrome (TS) have hypergonadotropic hypogonadism and need hormonal replacement for induction of puberty and then for maintaining secondary sex characteristics, attaining peak bone mass, and uterine growth. The optimal estrogen replacement regimen is still being studied. Evidence Acquisition: We conducted a systematic search of PubMed for studies related to TS and puberty. Evidence Synthesis: The goals of replacement are to mimic normal timing and progression of physical and social development while minimizing risks. Treatment should begin at age 11 to 12 years, with dose increases over 2 to 3 years. Initiation with low-dose estradiol (E2) is crucial to preserve growth potential. Delaying estrogen replacement may be deleterious to bone and uterine health. For adults who have undergone pubertal development, we suggest transdermal estrogen and oral progestin and discuss other approaches. We discuss linear growth, lipids, liver function, blood pressure, neurocognition, socialization, and bone and uterine health as related to hormonal replacement. Conclusion: Evidence supports the effectiveness of starting pubertal estrogen replacement with low-dose transdermal E2. When transdermal E2 is unavailable or the patient prefers, evidence supports use of oral micronized E2 or an intramuscular preparation. Only when these are unavailable should ethinyl E2 be prescribed. We recommend against the use of conjugated estrogens. Once progestin is added, many women prefer the ease of use of a pill containing both an estrogen and a progestin. The risks and benefits of different types of preparations, with examples, are discussed
Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone
To assess possible side-effects of GH treatment with supraphysiological
doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS)
during long term GH treatment and after discontinuation of GH treatment,
the results of oral glucose tolerance tests and hemoglobin A1c
measurements were analyzed in 68 girls with TS participating in a
randomized dose-response trial. These previously untreated girls, aged
2-11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4
IU/m2 x day (-0.045 mg/kg x day); group B, first year ,4 IU/m2 day;
thereafter, 6 IU/m2 x day (approximately 0.0675 mg/kg x day); group C,
first year, 4 IU/m2 x day; second year, 6 IU/m2 x day; thereafter, 8 IU/m2
x day (approximately 0.090 mg/kg x day). After the first 4 yr, girls 12 yr
of age or older started with 5 microg/kg BW-day 17beta-estradiol for
induction of puberty. To assess the effects of long term high dose GH
treatment on CH metabolism, the 7-yr data from the oral glucose tolerance
tests in 9 girls of group C were evaluated (group C1). To determine
whether the changes in CH metabolism during GH treatment would persist
after discontinuation of GH treatment, the data for 28 girls who had
reached adult height (group A, n = 9; group B, n = 10; group C, n = 9)
were evaluated at baseline, after 4 yr of GH treatment, and 6 months after
discontinuation of GH. Seven-year data for group C1 showed that glucose
levels did not significantly change during GH treatment, whereas fasting
insulin levels as well as glucose-induced insulin levels increased
significantly. The data for the 28 girls who were treated with GH for a
mean (SD) period of 85.3 (13.3) months demonstrated that the GH-induced
higher insulin levels decreased to values close to or equal to
pretreatment values after discontinuation of GH treatment. Changes in CH
variables were not significantly related to the GH dose. Hemoglobin A1c
levels never showed an abnormal value. The prevalence of impaired glucose
tolerance was low, and none of the girls developed diabetes mellitus. In
conclusion, long term GH treatment with dosages up to 8 IU/m2 x day in
girls with TS has no adverse effects on glucose levels, but induced higher
levels of insulin, indicating relative insulin resistance. The increased
insulin levels during long term GH treatment decreased after
discontinuation of GH treatment to values close to or equal to
pretreatment values. Although the reversibility of the effects of long
term GH is reassuring, the consequence of long term hyperinsulinism is
still unknown
[Mauriac syndrome--a rare complication of type 1 diabetes mellitus].
The treatment of children with type 1 diabetes mellitus has improved dramatically over the last few decades. The maintenance of acceptable metabolic control, nevertheless, remains challenging because the success of treatment is so dependent on patient compliance. Children with type 1 diabetes and poor metabolic control are at risk of developing Mauriac syndrome, a condition characterised by hepatomegaly, growth retardation and cushingoid features. A similar complication may occur in type-1 or type-2 adult diabetics; namely, glycogenic hepatopathy. We describe two children, a 12-year-old girl and a 16-year-old boy, who presented with classic symptoms of Mauriac syndrome. After metabolic control was achieved, reduction of hepatomegaly and the disappearance of cushingoid features were observed, proving the reversibility of the syndrome. Awareness that this syndrome still exists despite improved insulin therapy is crucial for earlier recognition and treatment