OBJECTIVES: Hypercortisolism in Cushing’s Disease (CD) is associated with significant comorbidities, which improve and in some cases are reversed with biochemical control (BC). The purpose of this study was to capture data describing comorbidity reductions with BC and estimate the potential cost savings associated with reversal. METHODS: Comorbidity reductions with BC were identified through a comprehensive literature search using CD AND epidemiology, morbidity, complications, BC and treatment outcomes as search terms.  Selected clinical studies detailed the relationship between comorbidity and BC in adults.  In the cost analysis, comorbidities were selected if reported in patients achieving BC.  Literature-based cost estimates were identified for CD-related comorbidities from the US payer perspective, and inflated to 2010 USD.  Cost ranges were reported as the difference between expected comorbidity costs in uncontrolled and controlled patients. Sensitivity analyses were conducted to also include possibly reversible comorbidities. RESULTS: Patients with CD experience comorbidities ranging from back pain (86%) to psychosis (1.4%).  Of 16 comorbidities identified in this study, seven were certainly reversible in CD patients achieving BC.  Hypertension and diabetes mellitus were reversed in 44% and 40% of patients achieving BC at 1 year. Psychiatric illness and nephrolithiasis were resolved in 76% and ~50% of CD patients.  In CD patients with reported impaired glucose tolerance and overweight/obesity, 60% and 37% of cases were resolved with BC.  The application of cost estimates to prevalence of each reversible comorbidity before BC yielded a total per-patient cost of $19,239-$27,600.  With BC, expected comorbidity costs ranged from $12,448-$18,312, representing a cost savings of $6,790-$9,288. Sensitivity analysis including possibly reversible comorbidities (like back pain, osteoporosis and vertebral fractures) produced estimated total cost savings of $10,571-$14,806 (incremental cost savings, $3,780-$5,518).  CONCLUSIONS: Comorbidity improvement and resolution in CD can be achieved with BC, which confers a commensurate cost savings to the health care payer.