Corticotroph tumor progression after adrenalectomy in Cushing's Disease: A reappraisal of Nelson's Syndrome.

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.

The Nelson's syndrome... revisited.

Adrenalectomy is a radical therapeutic approach to control hypercortisolism in some patients with Cushing's disease. However it may be complicated by the Nelson's syndrome, defined by the association of a pituitary macroadenoma and high ACTH secretion after adrenalectomy. This definition has not changed since the end of the fifties. Today the Nelson's syndrome must be revisited with new to criteria using more sensitive diagnostic tools, especially the pituitary magnetic resonance imaging. In this paper we will review the pathophysiological aspects of corticotroph tumor growth, with reference to the impact of adrenalectomy. The main epidemiological data on the Nelson's syndrome will be presented. More importantly, we will propose a new pathophysiological and practical approach to this question which attempts to evaluate the Corticotroph Tumor Progression after adrenalectomy, rather than to diagnose the Nelson's syndrome. We will discuss the consequences for the management of Cushing's disease patients after adrenalectomy, and will also draw some perspectives.