Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486.
A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.
Nieman
L K
LK
Chrousos
G P
GP
Kellner
C
C
Spitz
I M
IM
Nisula
B C
BC
Cutler
G B
GB
Merriam
G R
GR
Bardin
C W
CW
Loriaux
D L
DL
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy*; D004963:Estrenes / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D015735:Mifepristone; D013256:Steroids / Q000097:blood; D013739:Testosterone / Q000097:blood
D001786:Blood Glucose; D002352:Carrier Proteins; D004963:Estrenes; D013256:Steroids; D015735:Mifepristone; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D006854:Hydrocortisone