The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency.
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.


METHODS
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.
Deepak
D
D
Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospitals NHS Foundation Trust, Liverpool L9 7AL, UK. deepakd_s@yahoo.com
Daousi
C
C
Javadpour
M
M
Clark
D
D
Perry
Y
Y
Pinkney
J
J
Macfarlane
I A
IA
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001823:Body Composition / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D018836:Inflammation Mediators / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D018836:Inflammation Mediators; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I