title: Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer.
abstract: OBJECTIVE
  Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane-treated ACC patients yet.
  
  
  OBJECTIVE
  Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone.
  
  
  METHODS
  Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40-20-0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included.
  
  
  METHODS
  Serum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol.
  
  
  RESULTS
  Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l; P = 0·03) resulting in a generally lower AUC (98 ± 21 vs 149 ± 37 nmol h/l; P = 0·02).
  
  
  CONCLUSIONS
  40-20-0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment.
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Weigel
authors.affiliation: Endocrinology and Diabetes Unit, Department of Internal Medicine I, University Hospital of Wuerzburg, Wuerzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.affiliation: Department of Endocrinology and Diabetes, Adelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sherlock
authors.affiliation: Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland.
authors.forename: Amar
authors.initials: A
authors.lastname: Agha
authors.affiliation: Department of Endocrinology and Diabetes, Adelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin, Ireland.|Department of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland.
authors.forename: Lucy Ann
authors.initials: LA
authors.lastname: Behan
authors.affiliation: Department of Endocrinology, University of Leeds, Leeds, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.affiliation: Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.|Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.affiliation: Endocrinology in Charlottenburg, Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Beier
authors.affiliation: Endocrinology and Diabetes Unit, Department of Internal Medicine I, University Hospital of Wuerzburg, Wuerzburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Frey
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zopf
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany.|Endocrinology in Charlottenburg, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy*; D000309:Adrenal Insufficiency / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000627:therapeutic use*
chemical_list: D008939:Mitotane; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone