Endocrine Abstracts

Introduction: Long-term survivors of childhood-onset brain tumours have increased risk of premature vascular disease by mechanisms that remain unclear. We hypothesised that a thrombotic fibrin network profile is one mechanism for the increased vascular risk in this population.

Methods: We undertook a cross-sectional study in 33 patients with previous history of brain tumours and 33 age and sex-matched healthy controls. We performed clot structure analysis using a validated turbidimetric assay and also assessed plasma levels of thrombotic and inflammatory vascular markers including fibrinogen, C-reactive protein (CRP) and complement C3.

Results: Thirty-three patients (19 males, mean age 31.5±14.2 years), treated for primary brain tumours, were studied. All patients received cranial radiotherapy, while 75.8% and 39.4% had additional surgery and chemotherapy, respectively. 94% of patients had growth hormone deficiency, whereas gonadotrophin, ACTH and TSH deficiency was evident in 18%, 12% and 6%, respectively). The time from brain tumour diagnosis to the time of the study was 8.9±6.2 years. Patients had raised clot maximum absorbance (a measure of clot density) compared with controls (0.412±0.10 and 0.277±0.09 arbitrary units (AU) respectively; P<0.001), increased clot lysis time (an indicator of fibrinolysis potential) (3695±731 and 2720±636 seconds, respectively; P<0.001) and larger lysis area (1949±1390 and 906±704 AU, respectively; P<0.001). Despite differences in fibrin network characteristics, fibrinogen levels were similar in patients and controls (3.38±0.95 and 3.28±1.15 mg/ml, respectively; P=0.473). In contrast, plasma CRP was higher in patients (3.08±4.25 and 0.78±1.08 mg/l, respectively; P=0.006) with similar findings for C3 (0.75±0.13 and 0.67±0.13 mg/ml; P=0.027).

Conclusions: We demonstrate, for the first time, that survivors of brain tumours with hypopituitarism display a thrombotic fibrin network profile, providing one mechanism for increased vascular risk in this population. Further longitudinal studies are required to clarify whether optimisation of the hormonal profile results in amelioration of the thrombotic environment in this population.