Panel 1.

Complications of CD: Summary of Recommendations

Hypercoagulation

• There is currently no standard practice for preoperative or postoperative thromboprophylaxis in patients with CD. Some experts hold estrogen therapy in women who are awaiting surgery, but care should be taken if it was being used as contraception, because pregnancy also is associated with increased risk of thrombosis (LQ, DR)

• Prophylactic anticoagulation should be considered for patients at risk for VTE, including history of embolism or abnormal coagulation testing; severe preoperative hypercortisolism; current use of estrogen or oral contraceptives; poor mobility; extended preoperative or postoperative hospital stay; and high postoperative cortisol levels or cortisol over-replacement in patients with AI (MQ, SR)

• Early postoperative ambulation and use of compression stockings should be encouraged for all patients (HQ, SR)

• If thromboprophylaxis is administered, there was strong consensus for preference of low molecular weight heparin over oral anticoagulants given the long half-life of the latter and the lack of therapy to reverse their effect, which may be especially concerning in the preoperative setting (LQ, DR)

• Anticoagulants may be discontinued before surgery to minimize intraoperative bleeding risk, but the timing of when to stop and when to reinitiate after surgery is unclear (LQ, DR)

• Among meeting participants, recommended anticoagulation duration ranged in the preoperative setting from 2–4 days to 1–2 weeks, and in the postoperative setting from 1–2 days of the hospital stay up to 2–4 weeks or even longer to 2–3 months (LQ, DR)

• Thromboprophylaxis should not be routinely used in pediatric patients due to bleeding risk but reserved for selected patients

Cardiovascular Disease

• Evaluate, monitor, and treat according to current guidelines for patients at high risk for cardiovascular disease (HQ, SR)

• Management approach should be individualized (HQ, SR) based on the complications present (e.g., hypertension or hyperlipidemia) and care should be coordinated with primary care and cardiology physicians as needed (VLQ, DR)

Bone Disease

• Risk assessment for bone loss and fracture recommended in all patients (HQ, SR)

• Given the risk for fracture even in patients without osteoporosis, standard DXA alone may not be sufficiently informative; bone quality (microscanner or trabecular bone score) or morphometric vertebral assessment is recommended where available (HQ, SR) and can be useful in detecting subclinical fractures (HQ, SR), but might not be practical for all patients. The FRAX tool to assess fracture risk is not validated for CD

• Monitor and follow-up as for all adult high-risk populations (HQ, SR)

• Consider conventional osteoporosis treatments, e.g., bisphosphonates, for patients with persistent CD even if BMD is normal because of increased fracture risk due to cortisol excess (HQ, SR)

GH Deficiency

• There is currently no standard practice for whether, when, and how to test for GHD in adults with CD. As postoperative HPA axis recovery is often delayed, we recommend waiting at least 6–12 months after surgery before considering GHD assessment (MQ, SR)

• Patients with macroadenomas and more aggressive surgical resection are at higher risk for hypopituitarism; patients with 3 or more pituitary hormone deficiencies are more likely to have GHD and do not need dynamic testing (HQ, SR)

• Serum IGF-I level alone is not likely to be a reliable indicator of GHD, as levels can be in the lower half of the normal range on dynamic tests

• Accessibility of GH replacement may be an important factor in determining testing and treatment considerations. If GH replacement is implemented earlier than 2 years after pituitary surgery, we recommend retesting periodically to determine whether GH secretion has normalized upon HPA axis recovery (MQ, SR)

• As CS-associated myopathy does not spontaneously resolve during remission, physical rehabilitation is recommended for all patients (HQ, SR).

• In children, evaluate for GHD 3–6 months after surgery and immediately initiate GH replacement if needed to ensure proper growth

Abbreviations: AI, adrenal insufficiency; BMD, bone mineral density; CD, Cushing’s disease; DXA, dual x-ray absorptiometry; GHD, growth hormone deficiency; HPA, hypothalamus-pituitary-adrenal; VTE, venous thromboembolism.