OBJECTIVES: Cushing’s disease (CD), a rare pituitary disorder, is associated with significant morbidity and mortality, but the economic impact is unknown. This study assessed the annual healthcare costs and utilization of CD patients. METHODS: Administrative claims from 2004-2008 of a large population with commercial or Medicare-supplemental insurance in the US were analyzed. CD patients were those with medical claims for Cushing’s syndrome (ICD-9-CM: 255.0) and either benign pituitary adenoma (227.3) or hypophysectomy (07.6). Each CD patient was age- and gender-matched to four patients with non-functioning pituitary adenoma (NFPA) and ten population controls (PC). NFPA was identified as benign pituitary adenoma without Cushing’s syndrome, acromegaly (253.0) or hyperprolactinemia (253.1). Comorbid conditions and annual direct healthcare costs were compared between cohorts by calendar year. RESULTS: The study identified 877 CD patients (79% female; average age 43 years). Hypertension (43% [CD] vs. 24% [NFPA] vs. 17% [PC]), diabetes (29% vs. 13% vs. 7%) and hyperlipidemia (27% vs. 21% vs. 14%) were the most common comorbidities in CD patients and more prevalent than in NFPA patients and PC (all p<0.05). CD patients had significantly higher total healthcare costs than NFPA patients and PC in 2004-2008; the difference between cohorts increased over time. In 2008, average healthcare costs were $26,440 among CD patients, compared to $13,708 in NFPA patients and $5,954 in PC (both p<0.05). Approximately one-third of total costs among CD patients were attributable to CD-related services. CD patients were more likely to have inpatient admissions (20.7% vs. 15.8% [NFPA] vs. 7.1% [PC], both p<0.01), had more frequent outpatient hospital visits (6.5 vs. 3.8 vs. 1.8, both p<0.01), and received more medications than NFPA patients and PC (means: 10.0 vs. 7.4 vs. 4.7, both p<0.01). CONCLUSIONS: CD patients had more comorbidities than NFPA patients and PC, and incurred significantly higher annual healthcare costs.