Peripheral fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with growth hormone deficiency.
BACKGROUND
Increased mortality due to cardiovascular disease has been described in adult patients with untreated GH deficiency (GHD). GH replacement has been demonstrate to improve vascular reactivity and reverse early atherosclerotic changes in adults with GHD.


OBJECTIVE
Assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GHD at baseline and 1 year after GH replacement therapy.


METHODS
We studied 10 patients with GHD (five men and five women; aged 45.6 +/- 10.4 years) at baseline and 1 year after GH replacement therapy compared with a control group (nine men and 16 women) matched for age and body mass index (BMI). All subjects, patients and controls, were life-long nonsmokers, normotensive and nondiabetic. The following variables were recorded: anthropometric and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin (TAT) fragments and fibrin degradation product D-dimer, which were determined by an enzyme-linked immunosorbent assay (ELISA); IGF-I by radioimmunoassay (RIA); C-reactive protein (CRP) by highly sensitive immunonephelometry; E-selectin, P-selectin, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) by ELISA. The assessment of endothelial function in vivo was measured with a Doppler device.


RESULTS
Patients with GHD without GH substitution had higher hip/waist ratio and body fat than controls. Insulin, C-peptide and triglyceride concentrations were also higher. Our results demonstrated no difference in fibrinogen and in TAT fragment concentrations among patients and controls. E-selectin concentrations were higher in patients than in controls (26.1 +/- 11 vs. 10.7 +/- 6.2 microg/l, P = 0.0001). P-selectin, sICAM-1, sVCAM-1, IL-6, MCP-1 and CRP were similar in the two groups. Vascular reactivity and carotid intima-media thickness (IMT) were also similar in patients and controls. After 1 year of GH treatment we found no changes in biochemical parameters, fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function.


CONCLUSIONS
Adults with GHD show some subtle changes in soluble adhesion molecules but our data suggest no beneficial effects of GH over these markers in relationship to endothelial function. Factors other than GH treatment, such as differences in age, degree of obesity, the presence of diabetes mellitus and arterial hypertension or tobacco consumption, could explain the observed increase in markers of vascular risk in GH-deficient patients.
Gómez
José Manuel
JM
Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jmgs@csub.scs.es
Sahún
Manel
M
Vila
Ramon
R
Domènech
Pere
P
Catalina
Pablo
P
Soler
Juan
J
Badimón
Lina
L
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001823:Body Composition; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D013997:Time Factors; D014463:Ultrasonography
D015415:Biomarkers; D013006:Growth Hormone