Perioperative Recommendations for Cushing's Disease

Preoperative Considerations

Patients with Cushing's disease should be surgically intervened in specialized centers of excellence in pituitary tumors by an experienced neurosurgeon and with follow-up by a multidisciplinary team that includes a specialized endocrinologist to optimize results and reduce complications 1
Preoperative medical therapy is not routinely used in most patients with Cushing's disease, as there are no rigorous data to support its widespread use 2, 3
Inhibitors of adrenal steroidogenesis (such as ketoconazole or metyrapone) may be considered in specific cases, including patients with severe hypercortisolism 4, when surgery is delayed due to scheduling issues or other factors 5, or patients with potentially life-threatening complications related to hypercortisolism (metabolic, psychiatric, infectious, or cardiovascular/thromboembolic) 3, 4
Prophylactic anticoagulation should be considered for patients at risk of venous thromboembolism (VTE), including those with a history of embolism or abnormal coagulation tests 6, severe preoperative hypercortisolism 6, current use of estrogens or oral contraceptives 6, reduced mobility 6, prolonged pre- or postoperative hospital stay 6, or elevated postoperative cortisol levels 6
There is a strong consensus to prefer low-molecular-weight heparin over oral anticoagulants due to the long half-life of the latter and the lack of therapy to reverse their effect 6

Transsphenoidal surgery is the first-line treatment for patients with Cushing's disease 7
Remission, typically defined as postoperative serum cortisol <55 nmol/L (<2 μg/dL), is observed in approximately 80% of patients with microadenomas and 60% with macroadenomas when surgery is performed by an experienced surgeon 7
The highest remission rates are correlated with treatment in a high-volume center by an experienced surgeon 7, detection of the tumor on magnetic resonance imaging 7, non-invasive tumor 7, and tumor size <1 cm 7
Common complications include new-onset hypopituitarism (approximately 10% of patients) 7, permanent diabetes insipidus 7, cerebrospinal fluid leak 7, and venous thromboembolism (all <5% of patients) 7, with perioperative mortality <1% 7

Patients in remission require glucocorticoid replacement until recovery of the hypothalamic-pituitary-adrenal axis 7
Evaluation for recurrence should begin after recovery of the hypothalamic-pituitary-adrenal axis and then annually or sooner if clinically suspected 1

Monitoring and follow-up of patients treated with preoperative therapy can be challenging, as postoperative cortisol evaluations to determine surgical cure are not reliable 3, 5
Recurrence after successful surgery is characterized by the reappearance of clinical and biochemical characteristics of hypercortisolism after initial remission 1
Published recurrence rates vary between 5% and 35%, with half occurring within the first 5 years after surgery and the other half after up to 10 years or more 1