Abstract and Introduction
Patients with Cushing disease (CD) may present with both chronic and acute perioperative complications that necessitate multidisciplinary care. This review highlights several objectives for these patients before and after transsphenoidal surgery. Preoperative management includes treatment of electrolyte disturbances, cardiovascular comorbidities, prediabetes/diabetes, as well as prophylactic consideration(s) for thromboembolism and infection(s). Preoperative medical therapy (PMT) could prove beneficial in patients with severe hypercortisolism or in cases of delayed surgery. Some centers use PMT routinely, although the clinical benefit for all patients is controversial. In this setting, steroidogenesis inhibitors are preferred because of rapid and potent inhibition of cortisol secretion. If glucocorticoids (GCs) are not used perioperatively, an immediate remission assessment postoperatively is possible. However, perioperative GC replacement is sometimes necessary for clinically unstable or medically pretreated patients and for those patients with surgical complications. A nadir serum cortisol of less than 2 to 5μg/dL during 24 to 74 hours postoperatively is generally accepted as remission; higher values suggest nonremission, while a few patients may display delayed remission. If remission is not achieved, additional treatments are pursued. The early postoperative period necessitates multidisciplinary awareness for early diagnosis of adrenal insufficiency (AI) to avoid adrenal crisis, which may also be potentiated by acute postoperative complications. Preferred GC replacement is hydrocortisone, if available. Assessment of recovery from postoperative AI should be undertaken periodically. Other postoperative targets include decreasing antihypertensive/diabetic therapy if in remission, thromboprophylaxis, infection prevention/treatment, and management of electrolyte disturbances and/or potential pituitary deficiencies. Evaluation of recovery of thyroid, gonadal, and growth hormone deficiencies should also be performed during the following months postoperatively.
Cushing syndrome (CS), comprising all etiologies of cortisol excess, is associated with important morbidities including cardiovascular (CV), thromboembolic, metabolic, infectious, musculoskeletal, psychiatric, and other complications.[1–4] Cushing disease (CD), the most frequent cause of endogenous CS, is due to an adrenocorticotropin (ACTH)-producing corticotroph pituitary adenoma leading to cortisol overproduction. Mortality in patients with untreated CS is high and mostly due to CV, thromboembolic, and infectious causes.[1,2,5] The management of patients with CS is complex and requires clinicians to address multiple aspects of this multimorbid condition from the moment of initial diagnosis.
The first line treatment for most patients with CD is transsphenoidal pituitary surgery (TSS), which generally achieves remission in 70% to 90% of microadenoma cases but is lower for macroadenomas.[3,4] Surgery should ideally be performed in a high-volume center by an experienced pituitary surgeon.[3,4] While surgery is expected to induce remission and improve cortisol-related morbidities, the perioperative period, from the time of diagnosis until at least 3 months postoperatively, is marked by the highest rate of morbidity and mortality.[6,7] Therefore, it is crucial to assess and treat hypertension, hypokalemia, hyperglycemia/diabetes, as well as assess the risk of thromboembolic and infectious complications and use preventive measures to reduce this risk. Notably, the risk of complications such as stroke, thromboembolism, and sepsis could persist even during long-term remission.
Furthermore, besides management of complications, the immediate postoperative period is critical in assessment for surgical success. Adrenal insufficiency (AI) indicates postoperative remission, and requires adequate glucocorticoid (GC) replacement to prevent severe GC withdrawal symptoms or even adrenal crisis. Additionally, sodium derangements are common and require close monitoring and treatment.[3,9,10]
In this review, we discuss in detail the aforementioned aspects of care. We aim to provide comprehensive and evidence-based information to help clinicians with perioperative care of patients with CD (Figure 1).[4,9,11,12]
Suggested algorithm for perioperative management of Cushing disease. AI, adrenal insufficiency; DI, diabetes insipidus; DST, dexamethasone suppression test; GC, glucocorticoids, HPA, hypothalamic-pituitary-adrenal; I&O, intake and output; IPSS, inferior petrosal sinus sampling; LNSC, late-night salivary cortisol; Na+, sodium; SIADH, syndrome of inappropriate antidiuretic hormone; UFC, urinary free cortisol. *See Tables 1 and 2. Adjust antihypertensive and antihyperglycemic regimen proactively if remission is achieved postoperatively. Urine osmolality/specific gravity may be checked daily and/or as needed paired with serum sodium every 6 to 12 hours depending on local protocols.
J Endo Soc. 2022;6(3) © 2022 Endocrine Society