Alterations of haemostatic and fibrinolytic markers in adult patients withgrowth hormone deficiency and with acromegaly

Alterations of coagulation and fibrinolytic systems might contribute to the increased cardiovascular and cerebrovascular mortality observed in patient s with both chronic growth hormone (GH) excess (acromegaly) and deficiency (GHD). However, contrasting results have been so far reported. To assess th e importance of GH in modulating haemostatic system, several haemostatic va riables in patients with GHD and acromegaly were measured. Twenty-four adul t patients with GHD (8 childhood- and 16 adult-onset: age: 41+/-12 years, i nsulin like growth factor-I, IGF-I: 6.7+/-4 nmol/L), 10 non-diabetic acrome galic patients (age: 39 +/- 15 years; IGF-I: 109+/-37 nmol/L) and 64 health y volunteers age and sex-matched with cases were studied. The plasma levels of tissue-type plasminogen activator antigen (t-PA), prothrombin fragment 1+2(F1+2) and thrombin-antithrombin complex (TAT) were measured by ELISA. P lasminogen activator inhibitor type 1 (PAI-1) was measured by an immunoacti vity assay and fibrinogen by von Clauss method. GH levels were measured by IFMA and IGF-I by RIA. GHD patients had higher PAI-1 (12.7+/-16.7 vs 4.8 +/ -5.3 U/ml, p<0.01), fibrinogen (363+/-104 vs 291+/-71 mg/dL, p<0.05) and TA T levels (6.8+/-9 vs 3.6+/-2.8ng/ml, p<0.05) than controls. Taking the 95th percentile of the normal distribution in the control group as the cut-off point for normal plasma levels of the haemostatic variables, high PAI level s were found in 25% of patients with GHD (P<0.01) while high fibrinogen and TAT levels were observed in 21% (P<0.05). The alterations were mostly pres ent in patients with adult-onset GHD, with the exception of hyperfibrinogen aemia which was equally present in adult- and childhood-onset patients. Acr omeyalic patients had higher mean fibrinogen levels than controls (398+/-11 1 vs 291+/-71 mg/dL, p<0.05), 40% having hyperfibrinogenaemia (P<0.01, vs c ontrols). They also had t-PA levels lower than controls and GHD. No correla tions between hormonal and haemostatic variables were found. Body mass inde x and waist to hip ratio correlated positively with PAI-1 levels in GHD pat ients only. In conclusion, this study shows that several abnormalities of c oagulation variables (increased PAI-I, fibrinogen and TAT levels) are prese nt in patients with GHD. while only hyperfibrinogenaemia is found in patien ts with acromegaly. These changes do not appear to be directly related to I GF-I levels or to the degree of GH deficiency/excess. However, these abnorm alities may be an additional trigger for the development of coronary heart disease and thromboembolic complications mostly in patients with GHD.