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

OBJECTIVE GH deficiency (GHD) is usually associated with a higher incidence of cardiovascular disease (CVD). The aim of this study was to establish wh ether patients with GHD, like those with CVD, show an increase in fibrinoge n (FBG), type-1 plasminogen activator inhibitor (PAI-1), acute phase respon se proteins (APR), and soluble adhesion molecules. The effect of recombinan t human GH (rhGH) replacement, on these parameters was also investigated. PATIENTS AND DESIGN Concentrations of PAI-1 antigen (Ag), adhesion molecule s(s)E-selectin,P-s-selectin, and intercellular adhesion molecule-1 ((s)ICAM -1), FBG and levels of APR orosomucoid (ORM), and 'negative APR' transferri n (TRF) were established in 11 panhypopituitary (PHP) patients (eight men a nd three women, age median 39.0 years, body mass index (BMI) 27.49 +/- 3.89 kg/m(2)) before and after 12-month replacement with rhGH. Control values w ere obtained by examination of 33 healthy age and sex matched subjects (24 men and nine women with BMI 24.16 +/- 1.99 kg/m(2)). RESULTS 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 mu g/l; P = 0.001), E-s-selectin (72.42 +/- 28.35, vs. 42.80 +/- 12.60 mu g/l; P = 0.004), P-s -selectin (221.26 +/- 75.12, vs. 104.79 +/- 26.01 mu g/l; P = 0.001) (s)ICA M-1 (409.75 +/- 137.78, vs. 228.10 +/- 37.54 mu g/l; P =0.001), and lower l evels of TRF (2.14 +/- 0.40, vs. 2.76 +/- 0.39 g/l; P = 0.001) than control s. 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 (E -s-selectin 57.98 +/- 27.04 mu g/l, P = 0.01, P-s-selectin 121.74 +/- 50.42 mu g/l, P = 0.007; and (s)ICAM-1 279.95 +/- 88.32 mu g/l, P = 0.005), whic h 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. CONCLUSION rhGH replacement led to modulation of the 'inflammatory response ' in panhypopituitary patients. This modulation occurred locally at vascula r endothelium level where after rhGH replacement, E-s-selectin, P-s-selecti n and (s)ICAM-1 concentrations decreased, a similar effect as in the system ic inflammatory response, as was also apparent from the changes in acute ph ase response protein levels.