Higher hydrocortisone dose increases bilirubin in hypopituitary patients- Results from an RCT

Background Bilirubin has anti-oxidative and anti-inflammatory properties, which may explain its proposed protective effects on the development of cardiometabolic disorders. Glucocorticoids affect heme oxygenase regulation in vitro, which plays a key role in bilirubin production. Effects of variations in glucocorticoid exposure on circulating bilirubin levels in humans are unknown. Here we tested whether a higher hydrocortisone replacement dose affects circulating bilirubin in hypopituitary patients.

Materials and methods A randomized double-blind cross-over study (ClinicalTrials.gov, number NCT01546992) was performed in 47 patients with secondary adrenal failure [10-week exposure to a higher hydrocortisone dose (0.4-0.6 mg/kg body weight) vs. 10 weeks of a lower hydrocortisone dose (0.2-0.3 mg/kg body weight)].

Results Plasma total bilirubin was increased by 10% from 7 to 8 mu M in response to the higher hydrocortisone dose (P = 0.033). This effect was inversely related to age (P = 0.042), but was unaffected by sex, obesity and (replacement for) other hormonal insufficiencies. The higher hydrocortisone dose also resulted in lower alkaline phosphatase (P = 0.006) and aspartate aminotransferase activities (P = 0.001).

Conclusion Bilirubin is modestly increased in response to higher glucocorticoid exposure in humans, in conjunction with lower alkaline phosphatase and aspartate aminotransferase activities, which are supposed to represent biomarkers of a pro-inflammatory state and enhanced liver fat accumulation.