Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

Ezzat, Shereen; Fear, Simon; Rc, Gaillard; Gayle, C.; Marcovitz, Sorana; Mattioni, Thomas A.; Nussey, Stephen; Rees, A.; Svanberg, Elisabeth

doi:10.1530/eje.0.1490499

Cited by 14 publications

(18 citation statements)

References 30 publications

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“…Ezzat et al (26) have found in a group of GHD adults that the effects of GH on lipoproteins, cardiac function, and quality of life could not be predicted by changes in IGF-I levels, which were only associated with alterations in LBM, in line with the findings of our study. In a short-term study with a low GH dose (0.5 IU or 0.17 mg/day), Gillberg et al (16) have shown marked biological effects despite the fact that IGF-I levels did not normalize in many of their patients.…”

Section: Discussionsupporting

confidence: 92%

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

Boguszewski¹,

Meister²,

Zaninelli³

et al. 2005

eur j endocrinol

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Objective: We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone (GH), 0.6 IU (0.2 mg)/day, administered for 12 months to GH-deficient (GHD) adults. Design and methods: Prospective open-label study, using 18 GHD patients (11 women, 7 men; aged 21 -58 years). All investigations were performed at baseline and after 12 months. Body composition was determined by dual energy X-ray absorptiometry. Results: Total body fat decreased (2 1.74^2.87%) and lean body mass (LBM) increased (1.27^2.08 kg) after therapy (P , 0.05). Changes in truncal fat did not reach statistical significance, but a decrease varying from 0.72 to 2.78 kg (1 to 8.7%) was observed in 13 (72%) patients. Bone mineral density (BMD) increased at lumbar spine, total femur and femoral neck (P , 0.05). Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy (P , 0.05), and their changes were directly associated with values at baseline. Insulin levels increased and the insulin resistance index worsened at 12 months (P , 0.05). Median IGF-I S.D. score was 2 4.30 (range, 2 11.03 to 20.11) at baseline and 21.73 (range, 2 9.80 to 2.26) at 12 months. Normal ageadjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline. Changes in IGF-I levels were not correlated with any biological end point, except changes in LBM (r ¼ 0.53, P ¼ 0.02). Side effects were mild and disappeared spontaneously. Conclusions: One-year of a fixed low-dose GH regimen in GHD adults resulted in a significant reduction in body fat, total cholesterol and LDL-cholesterol, and a significant increase in LBM and BMD at lumbar spine and femur, regardless of normalization of IGF-I levels. This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index.European Journal of Endocrinology 152 67-75

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Section: Discussionsupporting

confidence: 92%

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

Boguszewski¹,

Meister²,

Zaninelli³

et al. 2005

eur j endocrinol

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“…Lower BMI at baseline predicted good response in LBM. This finding is in agreement with a previous study, which also demonstrated that patients with the lowest baseline BMI (below the lower quartile, 24.4 kg/m 2 ) benefited the most in terms of progressive and significant increases in LBM (38). Higher BF at baseline was also a weak predictor of good response in LBM.…”

Section: Predictorssupporting

confidence: 92%

“…With the cut-off values at the 60th and 40th percentiles, we had a higher degree of differentiation between the GR and PR response values. Consistent with other studies (37,38), the increase in LBM and decrease in BF were sustained after 12 months of GH replacement. Gender, baseline BMI, and BF were the most important predictors of LBM response to GH therapy.…”

Section: Predictorssupporting

confidence: 91%

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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

European Journal of Endocrinology

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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.

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“…To date, no data are available to quantify risk of under-treatment of such patients. Moreover, the optimal target IGF-I during GH replacement remains unclear (22,23). In our study, IGF-I levels rose in all patients and three of the four patients who failed to achieve IGF-I levels into the normal range nonetheless achieved substantial increments in IGF-I SDS of between þ 2.53 and þ 7.39 (Fig.…”

Section: Discussionmentioning

confidence: 57%

Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults

Mukherjee

Adams²,

Smethurst³

et al. 2005

eur j endocrinol

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Lean body mass (LBM) and total body water (TBW) are reduced in GH-deficient (GHD) adults and alter with GH replacement. Whether these parameters are interdependent and whether alterations in their homeostasis contribute to the perceived quality of life (QOL) deficit in GHD remains unclear. In this study, IGF-I, body composition by whole-body dual-energy X-ray absorptiometry, TBW by deuterium dilution (D 2 O) and two validated QOL instruments -psychological general well-being schedule (PGWB, generic, 6 domains; lower score worse QOL) and assessment of GH deficiency in adults (AGHDA, disease orientated; higher score worse QOL) were studied at baseline and after 3 and 6 months of GH replacement in thirty GHD adults. Patients with diabetes insipidus, and cardiac and renal failure were excluded. Median age-adjusted IGF-I standard deviation score increased from 2 3.40 (26.40 to 2 1.60) to 2 0.2 (2 1.88 to 0.78) (P , 0.0001) at a median daily GH dose of 0.4 mg. During treatment, LBM increased from 47.4^10.7 kg at baseline to 49.5^10.8 kg at 6 months (P ¼ 0.0008), and fat mass decreased from 28.0^12.1 kg at baseline to 27.2^12.6 kg at 6 months (P ¼ 0.0004). A non-significant trend towards an increase in TBW was observed (mean 1.7 kg, P ¼ 0.08). The PGWB score increased from 62.9^20.6 to 73.7^21.7 (P ¼ 0.0006). The AGHDA score decreased from 13.7^7.3 to 8.75^7.75 (P ¼ 0.0002). At each time point, a linear correlation between LBM and TBW was demonstrated, defined by TBW ¼ (0.972 £ LBM)-10.6. However, only a weakly positive correlation existed between the percentage changes in these variables (R ¼ 0.40, P ¼ 0.04). No correlations were demonstrated between QOL measures and body composition. The change in LBM with physiological GH replacement correlates weakly with change in TBW, therefore factors other than TBW may also contribute to the LBM changes. Improved QOL with GH replacement is not explained by favourable changes in body composition.European Journal of Endocrinology 153 661-668

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Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

Cited by 14 publications

References 30 publications

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults

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

Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults

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