Management of Cushing's syndrome due to ectopic adrenocorticotropin secretion with 1,ortho-1, para'-dichloro-diphenyl-dichloro-ethane: findings in 23 patients from a single center.
BACKGROUND
Effective treatment for the ectopic ACTH secretion syndrome (EAS) remains a therapeutic challenge. Immediate curative surgery of the responsible nonpituitary tumor is often not possible.


OBJECTIVE
The objective of the study was to evaluate 1,ortho-1, para'-dichloro-diphenyl-dichloro-ethane (O,p'DDD) therapy in EAS.


METHODS
Patients included 36 consecutive patients with EAS from a single center treated between 1990 and 2006. Twenty-three of these patients, including 18 women aged 53.7 +/- 12.9 yr (mean +/- sd), were treated with O,p'DDD. Patient follow-up was 8.04 +/- 9.6 yr.


RESULTS
A mean daily O,p'DDD dose of 3.3 +/- 1.2 g Lysodren equivalent was given for a mean duration of 1.8 +/- 2.1 yr. Urinary cortisol decreased from 2603 +/- 3443 microg/d before treatment to 79 +/- 169 microg/d at the time of maximal O,p'DDD efficacy. Urinary cortisol was normalized in 21 of the 23 patients. Adrenal insufficiency was observed in 20 patients. This was associated with clinical improvement of Cushing's syndrome manifestations, including diabetes, hypertension, and hypokalemia. O,p'DDD plasma levels were 10.4 +/- 6.5 microg/ml in the 12 patients tested at the time of adrenal insufficiency. Side effects were observed during the first 6 months in seven of 15 patients (46%). National Cancer Institute-Classification Common Toxicity Criteria grade 1 or 2 digestive or neurologic toxicity resolved after withdrawal or reduction of O,p'DDD. Careful monitoring was essential to long-term control, clinical improvement, and good tolerability. Medical control of the disease allowed the subsequent characterization of tumors in eight of 13 patients with initially occult tumors.


CONCLUSIONS
With close monitoring, O,p'DDD could be a potent medical treatment for long-term control and management of EAS.
Donadille
Bruno
B
Department of Endocrinology, Cochin Hospital, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France.
Groussin
Lionel
L
Waintrop
Charlotte
C
Abbas
Halim
H
Tenenbaum
Florence
F
Dugué
Marie-Annick
MA
Coste
Joël
J
Bertagna
Xavier
X
Bertherat
Jérôme
J
D000182:ACTH Syndrome, Ectopic / Q000150:complications*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012189:Retrospective Studies; D012463:Saliva / Q000737:chemistry
D008939:Mitotane; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone