Methylprednisolone increases plasma leptin levels in Graves' hyperthyroidism patients with active Graves' ophthalmopathy

Whether leptin, a product of the ob gene, can be stimulated by glucocortico id administration has been an issue of controversy. We investigated the eff ect of intravenous administration of methylprednisolone (500 mg/day x 3 day s) on plasma levels of leptin in 16 patients (female/male = 11/5) with Grav es' hyperthyroidism and active ophthalmopathy who received pulse therapy. S ignificant elevation of plasma leptin levels started at the eighth hour (13 .9 +/- 1.8 ng/mL, p = 0.042) and lasted until the 72nd hour (21.2 +/- 5.0 n g/mL, p = 0.009), as compared with basal levels (8.8 +/- 1.2 ng/mL). When m ethylprednisolone was replaced with oral prednisolone (10 mg three times pe r day x 2 weeks), no difference in plasma leptin levels was noted compared with basal measurement. Under methylprednisolone administration, a signific ant suppression of tumor necrosis factor-oc began at the 24th hour (8.1 +/- 1.3 pg/mL, p = 0.004) and lasted until the 48th hour (8.1 +/- 1.0 pg/mL, p = 0.008), as compared with basal measurement (121.5 +/- 1.5 pg/mL). Compar ed with basal levels (93 +/- 2 mg/dL), significant elevation in the plasma glucose level started at the third hour (135 +/- 10 mg/dL, p = 0.000) and l asted until the 72nd hour (110 +/- 4 mg/dL, p = 0.019). The timing of serum insulin elevation approximated that of plasma glucose (3 hours: 14 +/- 3 m u U/mL, p = 0.006) and lasted until the end of prednisolone administration (2 weeks: 12 +/- 2 mu U/mL, p = 0.044), when compared with basal levels (14 +/- 3 mu U/mL). We concluded that the parental administration of pharmacol ogical doses of methylprednisolone to patients with Graves' hyperthyroidism could acutely raise their plasma level of leptin.