Perioperative Management of Hypercortisolism in Knee Replacement Surgery

Key Perioperative Risks and Considerations

Hypercortisolism significantly increases perioperative risks, including hypercoagulability and venous thromboembolism (VTE), and requires aggressive preoperative optimization, with surgery ideally delayed until cortisol levels are controlled or at least 3 months after any intra-articular glucocorticoid injections, according to the Endocrine Society guidelines 1, 2
Patients with active hypercortisolism face multiple serious surgical complications, including infection risk due to immunosuppression from chronic cortisol excess, with a strength of evidence level of high 3
Cardiovascular complications, including hypertension and increased atherosclerosis risk, are present in over 80% of cases, and should be optimized according to standard guidelines from the American Heart Association 1, 4
Proximal myopathy with impaired muscle function may affect rehabilitation, and should be considered in the preoperative management strategy 3

Ideally, hypercortisolism should be treated and controlled before elective knee replacement to minimize complications, with a recommended treatment duration of at least 3 months, according to the Endocrine Society guidelines 1, 5
Medical therapy with steroidogenesis inhibitors, such as ketoconazole, metyrapone, or osilodrostat, should be considered for patients with severe hypercortisolism when surgery must be delayed, with a strength of evidence level of moderate 6, 7
For patients with Cushing's disease, transsphenoidal surgery is first-line treatment, achieving remission in approximately 80% of microadenomas and 60% of macroadenomas, according to the Endocrine Society guidelines 5

Prophylactic anticoagulation should be considered for all patients at risk for VTE, including those with severe preoperative hypercortisolism, poor mobility, or extended hospital stays, with a recommended duration of at least 2-4 weeks postoperatively, according to the American College of Chest Physicians guidelines 1, 5
Low molecular weight heparin is strongly preferred over oral anticoagulants due to the long half-life of oral agents and lack of reversal therapy, which is especially concerning perioperatively, with a strength of evidence level of high 1
Early postoperative ambulation and compression stockings should be used for all patients, with a recommended duration of at least 2-4 weeks postoperatively, according to the American College of Chest Physicians guidelines 1

If intra-articular glucocorticoid injections have been given, knee replacement should be delayed at least 3 months to minimize infection risk, according to the American Academy of Orthopaedic Surgeons guidelines 2
This timing consideration is particularly relevant since patients may have received IA injections for symptomatic management while awaiting surgery, with a strength of evidence level of moderate 2

For patients with known or suspected hypercortisolism requiring knee replacement, confirm diagnosis using 24-hour urinary free cortisol, nocturnal salivary cortisol, and/or 1 mg dexamethasone suppression test, according to the Endocrine Society guidelines 4
Assess severity and source by measuring plasma ACTH to differentiate ACTH-dependent from ACTH-independent causes, with a strength of evidence level of high 4
Optimize comorbidities, including diabetes, hypertension, and cardiovascular disease, according to standard guidelines from the American Diabetes Association, American Heart Association, and American College of Cardiology 1, 4