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Corticotroph Tumor Progression after Adrenalectomy in Cushing’s Disease: A Reappraisal of Nelson’s Syndrome

Departments of Endocrinology (G.A., F.K., J.B., X.B.), Biophysics and Hormonology (M.-A.D.), and Digestive and Endocrine Surgery (B.D.), Cochin Hospital, Faculté René Descartes, Paris 5 University, Centre de Référence des Maladies Rares de la Surrénale, and Department of Radiology A (H.B., S.S., P.L.), Statistics and Medical Informatics (J.C.), and Department of Endocrinology-Metabolism-Cancer (G.A., J.B., X.B.), Institut National de la Santé et de la Recherche Médicale U567 and Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Cochin Institute, 75014 Paris, France; and Department of Neuropathology (M.K.), Laboratoire R. Escourolle, Pitié Salpétrière Hospital, Paris 6 University, 75013 Paris, France

Address all correspondence and requests for reprints to: Xavier Bertagna, Department of Endocrinology, Cochin Hospital, 27, rue du Fg St. Jacques, 75014 Paris, France. E-mail: xavier.bertagna{at}cch.aphp.fr.

Context: Adrenalectomy is a radical treatment for hypercortisolism in Cushing’s disease. However, it may lead to Nelson’s syndrome, originally defined by the association of a pituitary macroadenoma and high plasma ACTH concentrations, a much feared complication.

Objective: The objective of the study was to reconsider Nelson’s syndrome by investigating corticotroph tumor progression based on pituitary magnetic resonance imaging scan and search for predictive factors.

Design: This was a retrospective cohort study.

Setting: The complete medical records of Cushing’s disease patients at Cochin Hospital were studied.

Patients: Patients included 53 Cushing’s disease patients treated by adrenalectomy between 1991 and 2002, without previous pituitary irradiation.

Measurements: Clinical data, pituitary magnetic resonance imaging data, and plasma ACTH concentrations for all patients and pituitary gland pathology data for 25 patients were recorded. Corticotroph tumor progression-free survival was studied by Kaplan-Meier, and the influence of recorded parameters was studied by Cox regression.

Intervention: There was no intervention.

Results: Corticotroph tumor progression ultimately occurred in half the patients, generally within 3 yr after adrenalectomy. A shorter duration of Cushing’s disease (adjusted hazard ratio: 0.884/yr), and a high plasma ACTH concentration in the year after adrenalectomy [adjusted hazard ratio per 100 pg/ml (22 pmol/liter): 1.069] were predictive of corticotroph tumor progression. In one case, corticotroph tumor progression was complicated by transitory oculomotor nerve palsy. During follow-up, corticotroph tumor progression was associated with the increase of corresponding ACTH concentrations (odds ratio per 100 pg/ml of ACTH variation: 1.055).

Conclusion: After adrenalectomy in Cushing’s disease, one should no longer wait for the occurrence of Nelson’s syndrome: modern imaging allows early detection and management of corticotroph tumor progression.

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