Use of ketoconazole in the treatment of a virilizing adrenocortical carcinoma.
Ketoconazole, an oral antimycotic agent, is known to have a potent inhibitory effect on adrenal steroid production. It was given at a dose of 1200 mg/day to a 52-year-old female patient with a virilizing adrenocortical carcinoma in order to achieve better metabolic control pre-operatively. Together with a rapid normalisation of hypertension and hyperglycemia, a dramatic fall was noticed in serum and urinary adrenal steroids after a few days. Levels of total testosterone (20 nmol/l), androstenedione (greater than 35 nmol/l) and DHEA-sulphate (greater than 28 nmol/l) fell to normal levels in 6 days. By contrast, levels of 17-OH-progesterone (30 nmol/l) and progesterone (2.45 nmol/l) increased slightly, indicating inhibition of adrenal 17,20-lyase. Cortisol (620 nmol/l at 08.00 h) fell to very low levels (50 nmol/l) on day 6 of the trial. We conclude that ketoconazole is very effective in suppression of adrenal tumoural steroidogenesis and merits consideration in pre-operative use. We warn against dangerous hypoadrenalism which seems to occur earlier in tumoural than in normal adrenal metabolism.
Department of Endocrinology, Middleheim Hospital, Antwerp, Belgium.
J A
JA
Verhelst
P
P
Druwé
P
P
van Erps
L J
LJ
Denis
C
C
Mahler
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006628:Hirsutism / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use*; D008875:Middle Aged
D000305:Adrenal Cortex Hormones; D012739:Gonadal Steroid Hormones; D007654:Ketoconazole