Endocrine Abstracts (2011) 26 P255

Quality of life and cortisol diurnal rhythm after 3 months of medical treatment for Cushing's disease

R van der Pas1, C de Bruin1, A Pereira2, J Romijn2, R Netea3, A Hermus3, P Zelissen4, F de Jong1, A van der Lelij1, W de Herder1, S Webb5, S Lamberts1, L Hofland1 & R Feelders1

1Erasmus Medical Center, Rotterdam, The Netherlands; 2LUMC, Leiden, The Netherlands; 3Radboud UMCN, Nijmegen, The Netherlands; 4Utrecht UMC, Utrecht, The Netherlands; 5Hospital Sant Pau, Barcelona, Spain.

Introduction: Cushing’s disease (CD) is characterized by various symptoms, amongst which fatigue, muscle weakness and depression. The chronic state of hypercortisolism severely impairs quality of life (QoL). In addition, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. Transsphenoidal surgery is the primary treatment for CD, but long-term remission rates are disappointing. We performed a prospective trial in which stepwise medical treatment was applied with the somatostatin-analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. We now report the effect of this regimen on QoL and CDR.

Methods: Seventeen patients with CD were treated for 80 days with pasireotide monotherapy or combination therapy with cabergoline and, if necessary, ketoconazole. Hereafter, patients continued medical therapy or underwent surgery. Using five questionnaires, QoL was assessed at baseline, day 80 and in the extension period and compared to literature-derived healthy controls.

Results: At baseline, QoL was significantly reduced compared to healthy controls according to 8/20 subscales. After 80 days, 15/17(88%) had normalized urinary free cortisol excretion. However, emotional reaction was the only QoL-related parameter that improved according to the Nottingham health profile (P<0.05). According to the RAND-36 questionnaire, patients reported more pain at day 80 (P<0.05), which might be a sign of steroid-withdrawal. QoL significantly improved in 8 patients after 764 days (mean) of biochemical remission after medical (n=3) or medical and surgical (n=5) treatment. In 7/17 patients, we observed a trend towards recovery of CDR, without any correlation with QoL.

Discussion: QoL in patients with untreated CD is significantly impaired compared to healthy controls from literature references. While no effect on QoL was found after 80 days of successful medical treatment, it seems to improve after a sustained period of biochemical remission. Finally, medical therapy for CD that blocks tumor secretory activity may initiate recovery of cortisol diurnal rhythm.