Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity?

OBJECTIVE In order to explore the mechanism of obesity in long-term survivo rs of childhood leukaemia, fat mass, lean body mass and serum leptin were a ssessed in a cohort of 32 (17 males) adults who had received cranial irradi ation (XRT) in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL), and compared with 35 age and body mass index (BMI) matche d young adults (18 male), DESIGN Thirty-one patients and 18 controls had fat mass and lean body mass assessed by dual x-ray absorptiometry (DEXA), using a lunar DPX-L scanner, Serum leptin concentrations were also measured in 27 patients and all contr ols, Growth hormone status had previously been determined using an insulin tolerance test and arginine stimulation test, Nine patients were classified as severe growth hormone (GH) deficient (group 1), 12 patients as GH insuf ficient (group 2) and 11 patients as normal (group 3), RESULTS BMI and absolute fat mass were not significantly different between the patients and controls regardless of their gender (P=0.1 and P=0.14 resp ectively), In contrast, absolute lean mass was significantly reduced (P<0.0 1) and leptin concentrations were significantly increased (P<0.001) in pati ents compared with controls, BMI, fat mass and leptin concentrations but no t lean mass were significantly different between the three GH status groups (P<0.01, P<0.01, P= 0.004, and P= 0.67 respectively). When leptin concentr ations were expressed per unit of fat mass, they were increased in the pati ents compared with the controls (P=0.03) with significant differences betwe en the GH status groups (P=0.004), being significantly higher in the severe GH deficient group, CONCLUSIONS Young adults who receive cranial irradiation in childhood are p rone to GH deficiency and hyperleptinaemia. The pathophysiological signific ance of the hyperleptinaemia remains to be established but it has occurred either as a consequence of radiation induced hypothalamic damage or GH defi ciency.