Lancet. 1989 Jun
3;1(8649):1221-5.
Jørgensen JO, Pedersen SA,
Thuesen L, Jørgensen J, Ingemann-Hansen T,
Skakkebaek NE, Christiansen JS.
Second University Clinic of Internal
Medicine, Aarhus Kommunehospital, Denmark.
A double-blind, placebo-controlled, crossover
study on the effects of 4 months' growth hormone (GH) treatment was
carried out in 22 GH-deficient adults (8 women, 14 men; mean [SEM]
age 23.8 [1.2] years). 1 patient was withdrawn because of oedema.
Mean total body weight of the other 21 did not change, whereas mean
muscle volume of the thigh, estimated by computerised tomography
(CT), was significantly higher after GH than after placebo (70.0
[3.7] vs 66.3 [3.1] ml/0.8 cm cross-sectional slice). The mean
adipose tissue volume of the thigh and subscapular skinfold
thickness fell significantly during GH treatment. Growth hormone
caused a small increase in the isometric strength of the quadriceps
muscles and a significant rise in exercise capacity (60.8 [7.2] vs
54.2 [6.6] kJ). The heart rate both at rest and after maximum
exercise was low during the placebo period and increased
significantly during GH treatment. Blood pressure and
echocardiographic wall mass of the left ventricle did not change
during the study. Growth hormone increased both mean glomerular
filtration rate and renal plasma flow from a subnormal level on
placebo to a level comparable with that of an age-matched control
group. The filtration fraction did not change. Urinary albumin
excretion was in the low normal range and was not affected by GH
treatment. Finally, GH treatment normalised mean circulating levels
of insulin-like growth factor 1 (IGF-1), which were low after the
placebo period (96 [9] micrograms/l placebo; 224 [28] micrograms/l
GH). These findings suggest that GH, in a conventional replacement
dose, has several potentially beneficial effects in GH-deficient
adults and therefore encourage future long-term trials.
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Eur J Endocrinol. 1994 Mar;130(3):224-8.
-
Jørgensen JO, Thuesen L,
Müller J, Ovesen P, Skakkebaek NE,
Christiansen JS.
Medical Department M (Diabetes and
Endocrinology), Aarhus Kommunehospital, Denmark.
Growth hormone (GH) replacement therapy in
several controlled short-term trials have shown unanimous
beneficial effects on body composition and other features. To
evaluate more long-term effects we report data from 3 years of
uninterrupted GH therapy in 10 GH-deficient adults who had all
completed a previous double-blind placebo-controlled study and
who also had been studied after 16 months of open GH therapy. No
further increase in linear height was observed. The initial
increase in thigh muscle volume was maintained after 3 years of
GH therapy. A slight increase in body weight and thigh fat
volume was recorded. Exercise capacity and isometric muscle
strength were increased significantly compared to the initial
placebo period. This was associated with stabilized levels of
resting heart rate and blood pressure. Glycosylated haemoglobin
levels were normal and did not change during the study. A
standard oral glucose tolerance test performed at the end of the
study revealed no evidence of glucose intolerance. No
side-effects were reported. Compared to an age- and sex-matched
group of healthy untreated subjects, thigh muscle volume,
exercise capacity and isometric muscle strength had become
normalized from subnormal levels after 3 years of GH therapy. We
conclude that long-term GH replacement therapy in GH-deficient
adults is associated with preserved beneficial effects on body
composition and physical performance, resulting in a near
normalization of several previously abnormal features and adding
new merits to this treatment modality.
-
-
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Clin
Endocrinol (Oxf). 1999 Jul;51(1):53-60.
Rodríguez-Arnao J, Jabbar A,
Fulcher K, Besser GM, Ross RJ.
Department of Endocrinology, St Bartholomew's
Hospital, London, UK.
OBJECTIVES: Adults with GH deficiency complain
frequently of low energy levels resulting in a low perceived quality
of life. Body composition is altered, with increased fat mass and
decreased lean body mass, and muscle strength is reduced. The aims
of this study were to determine the effects of GH replacement on
physical performance and body composition in GH deficient (GHD)
adults. STUDY DESIGN: The study consisted of a 6-month randomised,
double-blind, placebo controlled study of the administration of GH
(0.25 IU/Kg/week (0.125 IU/kg/week for the first four weeks))
followed by a 6-month open phase of GH therapy. PATIENTS:
Thirty-five GHD adults (17F), mean age 39.8 years (range 21.1-59.9),
on conventional replacement therapy as required. METHODS: Maximum
aerobic capacity was measured using an incremental walking test to
volitional exhaustion on a motorized treadmill. Quadriceps muscle
strength was assessed by measuring maximum voluntary contractions
and body composition by dual energy X-ray absorptiometry (DEXA).
RESULTS: There were no statistically significant changes in
quadriceps muscle strength between the GH and placebo groups. In
both groups, there was a significant increase in quadriceps muscle
strength compared to baseline during the double-blind period (GH
group: P = 0.016; placebo group: P = 0.048). Compared to baseline,
muscle strength was further improved in the GH treatment group after
12 months of treatment (P = 0.007). No further improvement was noted
in the placebo group after 6 months on open GH treatment. In the
placebo group, maximum aerobic capacity decreased during the placebo
period (P = 0.017). No significant change was observed in the GH
group. During open GH treatment the previously placebo treated group
had a significant increase of maximum aerobic capacity (P < 0.049)
whereas no significant improvement could be seen in the GH group. In
the GH group there was a significant increase in lean body mass (P =
0.001) and a significant decrease in fat mass (P < 0.001). No
statistically significant changes were noted in the placebo group:
the differences in these changes between treatment groups were
statistically significant (lean body mass: P = 0.009; fat mass: P <
0.001). The changes in body composition in the GH group during the 6
month placebo-controlled period were maintained during continued
open treatment. Similar changes in body composition to those
observed in the GH group during the 6 month placebo-controlled
period were also seen in the placebo group once the patients
received GH treatment. CONCLUSIONS: Our data show that GH
replacement in GH deficient adults is associated with favourable
changes in body composition, which could be important in the long
term health outcome and physical activity of GH deficient patients.
Our data support the concept that GH therapy alone, in the absence
of some form of exercise programme, may increase the amount of lean
tissue but not the quality or functional capacity of this tissue and
it may be that training, in addition to GH therapy, may be necessary
to significantly increase physical performance in these patients. We
suggest that future trials with GH therapy and general approaches to
the treatment of GH deficiency should include a planned activity
programme as an approach to health improvement in these patients.
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J Clin Endocrinol Metab. 2000 Oct;85(10):3762-9.
Chrisoulidou A, Beshyah SA,
Rutherford O, Spinks TJ, Mayet J, Kyd P,
Anyaoku V, Haida A, Ariff B, Murphy M,
Thomas E, Robinson S, Foale R, Johnston
DG.
Department of Clinical Physics, Imperial
College School of Medicine, St. Mary's Hospital, London, United
Kingdom.
Short-term studies of GH replacement in adult
hypopituitarism have usually demonstrated beneficial effects on body
composition and circulating lipids, with neutral or occasionally
adverse effects on glucose tolerance. Fasting hyperinsulinemia has
been reported. GH effects on cardiac function have been variable.
The effects of long-term GH therapy, taking into account the
consequences of increasing age, are not fully known. Thirty-three
hypopituitary, initially middle-aged adults were studied over a 7-yr
period; 12 patients took GH therapy (mean, 0.7 mg daily)
continuously (group A); 11 took GH for only 6-18 months, a minimum
of 5 yr previously (group B); and 10 patients never received GH
therapy (group C). Other pituitary replacement was maintained.
Effects on anthropometry, body composition (by bioimpedance
analysis, total body potassium, and dual energy x-ray absorptiometry),
circulating lipids, glucose and insulin concentrations, cardiac
2-dimensional and Doppler echocardiography, and exercise tolerance
were assessed before and after the treatment period. Continuous GH
therapy had no significant effect on body weight, but it prevented
the increase in waist circumference and waist to hip ratio that
occurred in the patients without GH substitution (waist to hip
ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group
B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH
effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P <
0.005 for GH effect). A GH-induced decrease in subscapular skinfold
thickness was also observed. By bioimpedance analysis, GH therapy
caused an increase in total body water and fat-free mass, and a
decrease in the percent body fat. Although changes occurred with
time in all groups, no significant additional GH therapy effects
were observed on glucose tolerance, insulin concentrations, lipid
levels, cardiac dimensions, echocardiographic diastolic function, or
exercise tolerance. In conclusion, prolonged GH substitution in
middle-aged hypopituitary adults causes a sustained improvement in
body composition. Other benefits, e.g. on lipid levels and exercise
tolerance, were not apparent at 7 yr when comparisons were made with
GH-untreated hypopituitary controls. Potentially adverse effects on
glucose tolerance and insulinemia did not develop with prolonged GH
therapy.
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