TY - JOUR
T1 - Rapid control of severe neoplastic hypercortisolism with metyrapone and ketoconazole
AU - Corcuff, Jean Benoît
AU - Young, Jacques
AU - Masquefa-Giraud, Pauline
AU - Chanson, Philippe
AU - Baudin, Eric
AU - Tabarin, Antoine
N1 - Publisher Copyright:
© 2015 European Society of Endocrinology.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Context: Severe Cushing's syndrome elicited by ectopic ACTH syndrome (EAS) or adrenal carcinoma (ACC) can threaten life in the short term. The effectiveness of oral administration of the inhibitors of steroidogenesis ketoconazole and metyrapone in this situation is poorly described. Objective: To report the short-term effectiveness and tolerability of metyrapone and ketoconazole elicited either by EAS or by ACC in patients exhibiting severe hypercortisolism. Design: Retrospective analysis of data obtained for patients with urinary free cortisol (UFC) level estimated to be fivefold the upper limit of the normal range (ULN). Patients and settings: A total of 14 patients with EAS and eight with ACC treated in two tertiary-care university hospitals. Intervention: Metyrapone and ketoconazole treatment in combination (along with symptomatic treatments for co-morbidities). Main outcome: Evolution of clinically relevant endpoints (blood pressure, kalaemia and glycaemia) and biological intensity of hypercortisolism 1 week and 1 month after starting steroidogenesis inhibition. Results: After 1 week of treatment, median UFC fell from 40.0 to 3.2 ULN and from 16.0 to 1.0 ULN in patients with EAS and ACC respectively. Median UFC after 1 month of treatment was 0.5 and 1.0 ULN in patients with EAS and ACC respectively and UFC values were normal in 73 and 86% of patients respectively. Clinical status improved dramatically along with kalaemia, glycaemia and blood pressure, allowing a decrease in the relevant treatments. Side effects were minimal and only two patients (one EAS and one ACC) experienced plasma transaminase elevations necessitating ketoconazole withdrawal. Conclusion: Metyrapone-ketoconazole combination therapy is well tolerated and provides rapid control of endocrine cancer-related life-threatening hypercortisolism.
AB - Context: Severe Cushing's syndrome elicited by ectopic ACTH syndrome (EAS) or adrenal carcinoma (ACC) can threaten life in the short term. The effectiveness of oral administration of the inhibitors of steroidogenesis ketoconazole and metyrapone in this situation is poorly described. Objective: To report the short-term effectiveness and tolerability of metyrapone and ketoconazole elicited either by EAS or by ACC in patients exhibiting severe hypercortisolism. Design: Retrospective analysis of data obtained for patients with urinary free cortisol (UFC) level estimated to be fivefold the upper limit of the normal range (ULN). Patients and settings: A total of 14 patients with EAS and eight with ACC treated in two tertiary-care university hospitals. Intervention: Metyrapone and ketoconazole treatment in combination (along with symptomatic treatments for co-morbidities). Main outcome: Evolution of clinically relevant endpoints (blood pressure, kalaemia and glycaemia) and biological intensity of hypercortisolism 1 week and 1 month after starting steroidogenesis inhibition. Results: After 1 week of treatment, median UFC fell from 40.0 to 3.2 ULN and from 16.0 to 1.0 ULN in patients with EAS and ACC respectively. Median UFC after 1 month of treatment was 0.5 and 1.0 ULN in patients with EAS and ACC respectively and UFC values were normal in 73 and 86% of patients respectively. Clinical status improved dramatically along with kalaemia, glycaemia and blood pressure, allowing a decrease in the relevant treatments. Side effects were minimal and only two patients (one EAS and one ACC) experienced plasma transaminase elevations necessitating ketoconazole withdrawal. Conclusion: Metyrapone-ketoconazole combination therapy is well tolerated and provides rapid control of endocrine cancer-related life-threatening hypercortisolism.
UR - http://www.scopus.com/inward/record.url?scp=84927667885&partnerID=8YFLogxK
U2 - 10.1530/EJE-14-0913
DO - 10.1530/EJE-14-0913
M3 - Article
C2 - 25624013
AN - SCOPUS:84927667885
SN - 0804-4643
VL - 172
SP - 473
EP - 481
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 4
ER -