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 glucocorticoid administration has been an issue of controversy. We investigated the effect of intravenous administration of methylprednisolone (500 mg/day × 3 days) on plasma levels of leptin in 16 patients (female/male = 11/5) with Graves' hyperthyroidism and active ophthalmopathy who received pulse therapy. Significant 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 ng/mL, p = 0.009), as compared with basal levels (8.8 ± 1.2 ng/mL). When methylprednisolone was replaced with oral prednisolone (10 mg three times per day × 2 weeks), no difference in plasma leptin levels was noted compared with basal measurement. Under methylprednisolone administration, a significant suppression of tumor necrosis factor-α 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 (12.5 ± 1.5 pg/mL). Compared 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 lasted 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 µU/mL, p = 0.006) and lasted until the end of prednisolone administration (2 weeks: 12 ± 2 µU/mL, p = 0.044), when compared with basal levels (14 ± 3 µU/mL). We concluded that the parental administration of pharmacological doses of methylprednisolone to patients with Graves' hyperthyroidism could acutely raise their plasma level of leptin.

Key words

Hyperinsulinemia - Hyperthyroidism - Leptin - Methylprednisolone - Tumor Necrosis Factor alpha