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The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency.
Growth Horm IGF Res. 2010 Jun; 20(3):220-5.GH

Abstract

BACKGROUND

Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited.

OBJECTIVE

To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease.

DESIGN

Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR.

RESULTS

GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR.

CONCLUSIONS

Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population.

Authors+Show Affiliations

Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospitals NHS Foundation Trust, Liverpool L9 7AL, UK. deepakd_s@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

20185347

Citation

Deepak, D, et al. "The Influence of Growth Hormone Replacement On Peripheral Inflammatory and Cardiovascular Risk Markers in Adults With Severe Growth Hormone Deficiency." Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, vol. 20, no. 3, 2010, pp. 220-5.
Deepak D, Daousi C, Javadpour M, et al. The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Growth Horm IGF Res. 2010;20(3):220-5.
Deepak, D., Daousi, C., Javadpour, M., Clark, D., Perry, Y., Pinkney, J., & Macfarlane, I. A. (2010). The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, 20(3), 220-5. https://doi.org/10.1016/j.ghir.2010.02.002
Deepak D, et al. The Influence of Growth Hormone Replacement On Peripheral Inflammatory and Cardiovascular Risk Markers in Adults With Severe Growth Hormone Deficiency. Growth Horm IGF Res. 2010;20(3):220-5. PubMed PMID: 20185347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. AU - Deepak,D, AU - Daousi,C, AU - Javadpour,M, AU - Clark,D, AU - Perry,Y, AU - Pinkney,J, AU - Macfarlane,I A, Y1 - 2010/02/24/ PY - 2009/10/14/received PY - 2010/01/27/revised PY - 2010/02/01/accepted PY - 2010/2/27/entrez PY - 2010/2/27/pubmed PY - 2010/9/21/medline SP - 220 EP - 5 JF - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JO - Growth Horm. IGF Res. VL - 20 IS - 3 N2 - BACKGROUND: Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited. OBJECTIVE: To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease. DESIGN: Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR. RESULTS: GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR. CONCLUSIONS: Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population. SN - 1532-2238 UR - https://www.unboundmedicine.com/medline/citation/20185347/The_influence_of_growth_hormone_replacement_on_peripheral_inflammatory_and_cardiovascular_risk_markers_in_adults_with_severe_growth_hormone_deficiency_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-6374(10)00019-5 DB - PRIME DP - Unbound Medicine ER -