Bruno Donadille, Lionel Groussin, Charlotte Waintrop, Halim Abbas, Florence Tenenbaum, Marie-Annick Dugué, Joël Coste, Xavier Bertagna, and Jérôme Bertherat*
Reference Center for Rare Adrenal Diseases and Departments of Endocrinology (B.D., L.G., C.W., X.B., J.B.), Toxicology (H.A.), Biophysics and Hormonology (F.T., M.-A.D.), and Biostatistics (J.C.), Assistance Publique-Hôpitaux de Paris, Cochin Hospital, and Institut National de la Santé et de la Recherche Médicale Unité 567 (L.G., X.B., J.B.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut Cochin, Paris 75014, France; and Faculté de Médecine (B.D., L.G., C.W., F.T., M.-A.D., J.C., X.B., J.B.), Paris Descartes University 75005 Paris, France
* To whom correspondence should be addressed. E-mail: email@example.com.
Context: 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.
Design and Patients: 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 ?g/d before treatment to 79 ± 169 ?g/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 ?g/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.
Conclusion: With close monitoring, O,p'DDD could be a potent medical treatment for long-term control and management of EAS.