Discontinuation Of Growth Hormone Therapy Research Articles

Growth hormone deficiency in children and young adults.

Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

What happens when growth hormone is discontinued at completion of growth? Metabolic aspects.

Continuing growth hormone (GH) replacement therapy in patients with childhood-onset GH deficiency (GHD) that persists into adulthood is an emerging issue. The prospective, long-term metabolic consequences of discontinuing GH therapy in adolescent patients with childhood-onset GHD and short stature have only recently been reported. These studies demonstrate that serum concentrations of total cholesterol, low-density lipoprotein-cholesterol and apolipoprotein B are higher in adolescents in whom severe GHD continues into adulthood. Upon discontinuation of GH therapy, serum concentrations of high-density lipoprotein-cholesterol have been found to decrease in patients with severe GHD and increase in patients regarded as GH sufficient when retested for GHD. Furthermore, total body fat and truncal fat mass increase after discontinuation of GH in both these patient groups, but more markedly in the patients with severe GHD. In adolescents with severe GHD persisting into adulthood, the discontinuation of GH therapy produces, over a period of 2 years, the accumulation of important cardiovascular risk factors that are associated with GHD in adults. Continuing replacement therapy into adulthood should therefore be considered.

Unfavourable impact of growth hormone (GH) discontinuation on body composition and cholesterol profiles after the completion of height growth in GH-deficient young adults.

Growth hormone (GH) plays an important role in the regulation of body composition and metabolism. GH deficiency is associated with obesity and hypercholesterolemia, which respond to GH treatment. In this study we evaluated changes in body composition and cholesterol profiles after discontinuation of GH therapy to assess atherogenic risk factors in GH-deficient patients. We studied 18 male patients with GH deficiency 17-20 years of age at the time of discontinuing GH therapy. Body composition and cholesterol were measured 6 months before discontinuation of GH therapy with a weekly dose of 0.5 IU/kg (approximately 0.19 mg/kg), and immediately, 2 months, and 6 months after the end of GH therapy. Two months after termination of GH therapy the percentage of body fat and fat mass increased from 7.4% to 9.4% and from 3.8 kg to 5.0 kg, respectively, and remained high thereafter. Lean body mass decreased gradually, but the change was not significant. Lean body mass: fat mass ratio decreased from 14.7 at termination of GH therapy to 10.9 at the end of study. Total cholesterol (TC) showed a significant linear increase from 156 mg/dl immediately after discontinuation to 169 mg/dl 6 months after discontinuation of GH, whereas high-density lipoprotein cholesterol (HDLC) showed no change during the study. The TC to HDLC ratio showed a slight but insignificant trend toward an increase. There were no significant changes in any variables during the last 6 months of GH therapy. GH therapy in patients with GH deficiency can reduce risk factors for obesity-related diseases and atherosclerosis. These beneficial effects are reversed after discontinuation of GH therapy. Further long-term studies of the effects of the GH withdrawal on lipid profiles, adiposity and life expectancy must be performed.

Changes in Levels of Serum and Urinary Collagen-Related Substances in Growth Hormone Deficient Children Following Discontinuation of Growth Hormone Therapy

Changes in Levels of Serum and Urinary Collagen-Related Substances in Growth Hormone Deficient Children Following Discontinuation of Growth Hormone Therapy

Rapid decrease of urinary pyridinoline excretion in growth hormone deficient children following discontinuation of growth hormone therapy

In order to examine the effect of growth hormone on urinary pyridinoline excretion, 32 patients with complete or partial growth hormone deficiency had their urinary pyridinoline excretion measured while receiving growth hormone and for 14 days after it was discontinued. There was a significant positive correlation between increases in growth velocities during the first year of growth hormone administration compared to before it, and the ratio of the urinary pyridinoline excretion levels while receiving growth hormone to those after discontinuation. Therefore, urinary pyridinoline excretion rapidly decreased in patients with growth hormone deficiency when the administration of growth hormone was stopped. Exogenous growth hormone appears to stimulate bone resorption in these patients.

Growth of short children during and after discontinuation of growth hormone therapy

Growth of short children during and after discontinuation of growth hormone therapy

Effects of Growth Hormone Replacement Therapy on Body Composition and Metabolic Indices in Patients with Growth Hormone Deficiency

Growth hormone (GH) is important in the regulation of fat, carbohydrate, and protein metabolism. These metabolic effects subsequently affect health risk factors, such as body composition, atherogenic risk factors, and glucose intolerance. GH deficiency is associated with obesity which reportedly responds to GH treatment. Children and adults with GH deficiency often have hypercholesterolemia and thus might be at increased risk of having atherosclerotic diseases in later life. In fact, adults with GH deficiency have been reported to have an increased mortality rate as a result of cardiovascular disease. On the other hand, the results of GH treatment in relation to carbohydrate metabolism are inconsistent in GH-deficient children. We evaluated the changes in health risk factors during GH replacement therapy in 40 children, 31 boys and 9 girls, with GH deficiency and compared our results with those in adult patients. In conclusion, GH replacement therapy in children and adults with GH deficiency can reduce health risk factors without altering glucose metabolism. These beneficial effects are reportedly reversed after the discontinuation of GH therapy. It therefore seems prudent to continue life-long GH replacement therapy in these patients.

Changes in body composition and bone density after discontinuation of growth hormone therapy in adolescence: an interim report

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual-energy X-ray absorptiometry in eight patients with GHD (age range, 13.8-17.5 years). Seven age-matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex-specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non-significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 +/- 11% (mean +/- SD) at baseline to 32 +/- 9.9% at 12 months (p = 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual-energy X-ray absorptiometry. The mean android:gynoid fat ratio increased, though non-significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Discontinuation of growth hormone therapy in growth-hormone-deficient patients: assessment of body fat mass using bioelectrical impedance.

The changes in body composition evaluated by the mean of bioelectrical impedance analysis (BIA) have been observed in a group of 16 male adolescents at the time of discontinuation of growth hormone (GH) therapy as well as at 6 and 12 weeks later. After reevaluation of their endocrine function, 6 patients (3 craniopharyngioma, 1 irradiation, 1 malformative, 1 idiopathic) had a profound persistent GH deficiency (maximum peak of GH under provocative tests < 5 ng/ml and low IGF-1 levels), while 10 patients had a normal somatotropic function. Both groups were comparable as far as age, weight and body mass index are concerned. Fat weight is significantly higher in the GH-deficient patients (9.9 +/- 2.6 kg) than in boys with a normal somatotropic function (6.0 +/- 1.1 kg) at the time of the discontinuation of GH therapy (p < 0.01). 3 months later, the increase in fat weight is significant only in the group of patients with severe GH deficiency (+4.1 +/- 2.2 kg; p < 0.05), the difference between the 2 groups (14.0 +/- 3.5 and 7.3 +/- 1.0 kg) becoming highly significant (p < 0.001). Lean body mass is lower in the GH-deficient patients and decreases slightly after GH discontinuation, while no significant variation is observed in the group of non GH-deficient boys. Although BIA assessment of body composition may be discussed when applied to GH-deficient subjects, these results show that such patients should be reevaluated after the discontinuation of GH therapy, including examination of the possible metabolic consequences of GH deficiency.

Limb regeneration following the discontinuation of growth hormone therapy in the hypophysectomized newt, Notophthalmus viridescens.

Untreated adult newts do not undergo normal limb regeneration following hypohysectomy. A fibrocellular dermal barrier (cicatrix) atypically forms between the apical epithelium and the underlying mesenchymal tissues. Historically, continuous administration of growth hormone or of prolactin in combination with thyroxine restored regenerative capacity to these newts. In a previous investigation, we demonstrated that the initial effect of these two hormone treatments, when administered on alternate days to hypophysectomized newts beginning eight days post-amputation, was to facilitate the erosion of the fibrocellular barrier and establish the epithelial mesenchymal interface that is observed in a regenerating limb. The present investigation was designed to evaluate the necessity of continuous hormone therapy to maintain limb regeneration in hypophysectomized newts. One, two, or three injections of growth hormone or of prolactin in combination with thyroxine was administered on successive alternate days to hypophysectomized newts either immediately following limb amputation (ID) or beginning eight days post-amputation (DD). The ID and DD newts receiving one, two, or three injections of growth hormone showed evidence of regeneration to the digitiform stage by day 30 post-amputation, while those receiving prolactin and thyroxine underwent wound healing. While both hormone treatments initially promoted a dermis-free apical epithelium, only hypophysectomized newts that had received growth hormone were able to continue regenerating. We have, therefore, concluded that discontinuous growth hormone therapy is sufficient to initiate and maintain the conducive environment for limb regeneration to advanced stages in the hypophysectomized newt. While initiating this process, prolactin and thyroxine therapy on a discontinuous regime does not maintain regeneration. The direct and indirect role of growth hormone in supporting limb regeneration in normal and hypophysectomized newts is discussed.