Endocrine Abstracts (2008) 16 P382

Residual adverse vascular risk and oxidative stress in treated adult panhypopituitarism

Annice Mukherjee1, Val Charlton-Menys2, Peter Trainer1, Jelena Chobotova2, Paul Durrington1 & Stephen Shalet1

1Christie Hospital, Manchester, UK; 2University of Manchester, Manchester, UK.

Background: Adult hypopituitarism is associated with premature vascular mortality for which the underlying mechanisms are unknown but untreated GH deficiency is proposed as a potential contributor.

Objectives: To characterise vascular risk, including paraoxonase-1 (PON1; an antioxidant enzyme which preserves LDL against oxidation), in adults with treated panhypopituitarism.

Study subjects: The study had full ethics approval. Data are presented as mean±S.D. or median (quartiles). Twenty-one panhypopituitary adults (group 1, aged 45±15 years), on stable pituitary replacement (>9 months), including GH and 43 controls of similar age (group 2, age 49±11 years) were studied.

Results: IGF-I SDS pre-GH replacement was −4.9 (−7.3, −2.95) and on stable GH replacement was 0.2 (−0.68, 1.03) in group 1 (normal range −2 to +2). Nine patients (5 female, age 52±15 years) from group 1 had prolactin levels persistently below 50 mU/l. Median total daily glucocorticoid replacement was hydrocortisone 20 mg or equivalent. Triglycerides were higher in group 1 compared with group 2 (2.02 (0.98–5.1) vs 1.09 (0.48–5.7) mmol/l; P<0.001, as were CRP levels (3.0 (1.7–6.8) vs 1.1 (0.1–11.0) mg/l; P<0.005). HDL levels were lower in group 1 (1.17±0.28 vs 1.51±0.43 mmol/l; P<0.005) as was PON1 activity (60 (27–278) vs 129 (27–438) nmol/ml per min; P<0.005). Total cholesterol, calculated LDL, ApoB, ApoB/A1, Lp(a), adiponectin were similar between groups. BMI (32±6 vs 25±4 kg/m2; P<0.001) and insulin levels (26.5 (1–123.7) vs 15.9 (5.6–25.8) mU/ml; P<0.05) were significantly higher in group 1. Within group 1, insulin levels were lower in the prolactin deficient subgroup (21.3±19.9 vs 53.1±38.1 mU/ml, P=0.03) but prolactin levels correlated strongly with BMI (r=0.78; P<0.005) only in prolactin non-deficient subjects.

Conclusions: Treated adult hypopituitarism is associated with residual adverse vascular risk during stable optimised conventional pituitary replacement, including GH. The observations may relate to the presence of associated obesity. Lower PON1 activity in panhypopituitarism is of interest because reduced PON1 activity is associated with oxidative stress and increased cardiovascular risk.

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