Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing's disease

Cushing's disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (p < 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (p = 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.