Details

Autor(en) / Beteiligte

• Weigel, Marianne
• Hahner, Stefanie
• Sherlock, Mark
• Agha, Amar
• Behan, Lucy Ann
• Stewart, Paul M.
• Arlt, Wiebke
• Beier, Daniela
• Frey, Kathrin
• Zopf, Kathrin
• Quinkler, Marcus

Titel

Immediate versus modified release hydrocortisone in mitotane‐treated patients with adrenocortical cancer

Ist Teil von

• Clinical endocrinology (Oxford), 2017-04, Vol.86 (4), p.499-505

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary 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. Aim 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. Design 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.