The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition

108

Objective: Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro. Ghrelin is mainly produced in and released from the stomach but it is probably also produced in the hypothalamic arcuate nucleus. Whether pituitary GH release is under the control of ghrelin from the stomach and/or from the arcuate nucleus is not known. Moreover, no data on the feedback of GH on systemic ghrelin concentrations are available. It has recently been suggested that ghrelin may induce obesity. Design: In this study, we addressed the following two questions: a) are circulating ghrelin levels increased in human GH deficiency (GHD), and b) does GH treatment modify ghrelin levels in human GHD? Methods: The study group consisted of 23 patients with GHD. Eighteen had developed adult-onset GHD and five had developed GHD in their childhood (childhood-onset GHD). Ghrelin was measured with a commercially available radioimmunoassay. All measurements were performed twice, first at baseline, before the start of GH replacement therapy, and then again after one year of therapy. GH doses were adjusted every 3 months, targeting serum total IGF-I levels within the normal gender-and age-related reference values for the healthy population. Maintenance doses were continued once the target serum total IGF-I levels were reached. Results: The sum of skinfolds and body water increased significantly, body fat mass and percentage body fat decreased significantly and body mass index and waist-hip ratio were not significantly changed by one year of GH replacement therapy.Before the start of GH replacement therapy, mean value and range for fasting ghrelin in the studied GHD subjects tended to be lower in comparison with healthy subjects in the control group although the difference did not reach significance (GHD ghrelin mean 67.8 pmol/l, range 37.6-116.3 pmol/l; control mean 83.8 pmol/l, range 35.4 -132 pmol/l; P ¼ 0:11).One year of GH replacement therapy did not modify circulating ghrelin levels (ghrelin before GH therapy: 67.8 pmol/l, range after GH therapy: 65.3 pmol/l,; P ¼ 0:56). Conclusions: We did not observe elevated ghrelin levels in adult GHD subjects and GH replacement therapy did not modify circulating ghrelin levels, despite significant decreases in body fat mass and percentage body fat. It is conceivable that the lack of ghrelin modifications after long-term GH therapy was due to the reduction of adiposity and insulin on one hand, and increased GH secretion on the other. However, it is still possible that systemic ghrelin is involved in the development of obesity, both in normal and GHD subjects.

Section: Discussionmentioning

confidence: 99%

Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy

Janssen

Toorn

Hofland

et al. 2001

108

“…This approval was based on studies showing that GHD in adults is associated with adverse clinical symptoms such as an abnormal body composition with increased fat mass and reduced lean body mass, reduced muscle strength and physical performance, decreased bone mineral density, an adverse lipid profile and an impaired quality of life (4,5). Treatment with GH was reported to have beneficial effects in GHD adults (4)(5)(6)(7)(8)(9). Although data on mortality were very limited at that time, a study in adults with hypopituitarism showed that life expectancy was reduced due to cardiovascular disease, and the authors suggested that this was possibly a result of GHD (10).…”

Section: Introductionmentioning

confidence: 99%

Dutch National Registry of GH Treatment in Adults: patient characteristics and diagnostic test procedures

Nieuwpoort

Bunderen

Arwert

et al. 2011

Objective: The Dutch National Registry of GH Treatment in Adults was established in 1998 as an initiative of the Ministry of Health. The main goals were to gain more insight into long-term efficacy, safety, and costs of GH therapy (GHT) in adult GH-deficient (GHD) patients in The Netherlands. Methods: Baseline patient characteristics and diagnostic test procedures were evaluated. Results: Until January 2009 in roughly 10 years, 2891 patients (1475 men and 1416 women, mean age 43.5G16.5 years) were registered. GHD was of childhood-onset (CO) in over 20% of the patients and of isolated in 11%. The most common causes of GHD were pituitary tumors and/or their treatment, craniopharyngiomas, and idiopathic GHD. In 85% of the patients, a GH stimulation test was performed, in the majority an insulin tolerance test (ITT) (49%) or a combined GHRH-arginine test (25%). In 12% of the patients, IGF1 levels were %K2 S.D. combined with two or more additional pituitary hormone deficits, and in 2%, it concerned patients with CO-GHD continuing GHT in adulthood. Over the years, the test of first choice shifted from ITT toward GHRH-arginine test. Conclusion: Nearly, 2900 patients were included in the nationwide surveillance database of the Dutch National Registry of GH Treatment in Adults until January 2009. Baseline patient characteristics are comparable to that reported previously. In 85% of these patients, the diagnosis of GHD was established by provocative testing, particularly an ITT or a combined GHRH-arginine test, with an evident increase in the percentage of GHRH-arginine tests being performed in the last years.

“…However, it is well known that clinical response to GH varies greatly in both children and adults with GHD (1,2). In children, the primary efficacy of therapy is usually evaluated by growth velocity, whereas, in adults, the end points to define responses to GH therapy are variable and include serum insulin-like growth factor 1 (IGF1), body composition (BC), cardiovascular risk factors, and quality of life (QoL) (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

Barbosa

Korányi²,

Filipsson³

et al. 2010

Objective: Clinical response to GH therapy in GH-deficient (GHD) adults varies widely. Good predictors of treatment response are lacking. The aim of the study was to develop mathematical models to predict changes in serum IGF1 and body composition (BC) in response to GH therapy in GHD adults. Design and methods: One hundred and sixty-seven GHD patients (103 men, median age 50 years) were studied before and after 12 months of GH treatment. GH dose was tailored according to serum IGF1 concentrations. Good responders (GR) and poor responders (PR) to GH therapy were defined as patients with a response O60th and !40th percentile respectively, for changes in serum IGF1 levels (adjusted for GH cumulative dose) and in BC (lean body mass (LBM) and body fat determined using dual-energy X-ray absorptiometry). A logistic regression model was used to predict the probability of being a GR or PR. Results: In the IGF1 prediction model, men (odds ratio (OR) 5.62: 95% confidence interval 2.59-12.18) and patients with higher insulin levels (OR 1.06: 1.00-1.12) were more likely to be GR. The accuracy of the prediction model was 70%. In the BC model, men ) and GHD patients with lower LBM (OR 0.82: 0.73-0.92) and greater height (OR 1.23: 1.08-1.40) at baseline were more likely to be GR. The accuracy of the prediction model was 80%. Conclusion: Accurate mathematical models to predict GH responsiveness in GHD adults were developed using gender, body height, baseline LBM, and serum insulin levels as the major clinical predictors.