Increase of adhesion molecules, fibrinogen, type-1 plasminogen activator inhibitor and orosomucoid in growth hormone (GH) deficient adults and their modulation by recombinant human GH replacement.

Abstract

GH deficiency (GHD) is usually associated with a higher incidence of cardiovascular disease (CVD). The aim of this study was to establish whether patients with GHD, like those with CVD, show an increase in fibrinogen (FBG), type-1 plasminogen activator inhibitor (PAI-1), acute phase response proteins (APR), and soluble adhesion molecules. The effect of recombinant human GH (rhGH) replacement, on these parameters was also investigated. Concentrations of PAI-1 antigen (Ag), adhesion molecules sE-selectin, sP-selectin, and intercellular adhesion molecule-1 (sICAM-1), FBG and levels of APR orosomucoid (ORM), and 'negative APR' transferrin (TRF) were established in 11 panhypopituitary (PHP) patients (eight men and three women, age median 39.0 years, body mass index (BMI) 27. 49 +/- 3.89 kg/m2) before and after 12-month replacement with rhGH. Control values were obtained by examination of 33 healthy age and sex matched subjects (24 men and nine women with BMI 24.16 +/- 1.99 kg/m2). PHP patients had higher concentrations of ORM (0.80 +/- 0.25, vs. 0.61 +/- 0.20 g/l; P = 0.05), FBG (3.22 +/- 0.48, vs. 2.57 +/- 0.47 g/l; P = 0.001), PAI-1 Ag (97.12 +/- 33.23, vs. 44.11 +/- 21.40 microgram/l; P = 0.001), sE-selectin (72.42 +/- 28.35, vs. 42. 80 +/- 12.60 microgram/l; P = 0.004), sP-selectin (221.26 +/- 75.12, vs. 104.79 +/- 26.01 microgram/l; P = 0.001) sICAM-1 (409.75 +/- 137.78, vs. 228.10 +/- 37.54 microgram/l; P = 0.001), and lower levels of TRF (2.14 +/- 0.40, vs. 2.76 +/- 0.39 g/l; P = 0.001) than controls. After 12-month rhGH replacement the patients showed an increase of TRF (2.64 +/- 0.84 g/l, P = 0.037) and decrease of soluble adhesion molecules (sE-selectin 57.98 +/- 27.04 microgram/l, P = 0.01, sP-selectin 121.74 +/- 50.42 microgram/l, P = 0.007; and sICAM-1 279.95 +/- 88.32 microgram/l, P = 0.005), which then, similarly to the ORM (0. 67 +/- 0.12 g/l) and FBG level (2.82 +/- 0.51 g/l), did not statistically differ from the values in the control group. rhGH replacement led to modulation of the 'inflammatory response' in panhypopituitary patients. This modulation occurred locally at vascular endothelium level where after rhGH replacement, sE-selectin, sP-selectin and sICAM-1 concentrations decreased, a similar effect as in the systemic inflammatory response, as was also apparent from the changes in acute phase response protein levels.