Premium
Higher hydrocortisone dose increases bilirubin in hypopituitary patients‐ results from an RCT
Author(s) -
Werumeus Buning Jorien,
KootstraRos Jenny E.,
Brummelman Pauline,
Berg Gerrit,
Klauw Melanie,
Wolffenbuttel Bruce H. R.,
Beek André P.,
Dullaart Robin P. F.
Publication year - 2016
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12624
Subject(s) - bilirubin , alkaline phosphatase , medicine , endocrinology , hydrocortisone , glucocorticoid , chemistry , biochemistry , enzyme
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 NCT 01546992) 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 μM 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.