Retrospective review shows preoperative ACTH levels and dexamethasone test predict surgical remission in Cushing disease.
INTRODUCTION Cushing’s disease (CD), caused by ACTH-secreting pituitary adenomas, typically presents with chronic hypercortisolemia, causing significant morbidity [1]. Emerging evidence suggests success of biochemical remission with surgery is dependent on preoperative diagnostic thresholds in late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC), or 1-mg dexamethasone suppression test (DST) [2]. Bilateral inferior petrosal sinus sampling (BIPSS) is often performed to confirm central ACTH production, with IPS:P >2 at baseline or >3 after stimulation considered diagnostic [3]. CD remains incompletely characterized; discordant clinical and laboratory findings yield variable surgical outcomes. Objective: To validate previously proposed endocrine cutoffs predictive of surgical remission in a separate cohort. METHODS After IRB approval, we retrospectively reviewed all pituitary adenomas presenting with Cushing’s syndrome treated surgically at our institution over 10 years (n=55). We collected preoperative hormone studies, BIPSS and MRI findings, and outcomes. RESULTS Cushing adenomas fell into four categories: MRI(+)/pathology(+) (n=22), MRI(+)/pathology(-) (n=17), MRI(-)/pathology(+) (n=3), and MRI(-)/pathology(-) (n=13). Remission rates varied from 100% in MRI(-)/pathology(+) to 36.4% in MRI(-)/pathology(-) (p=0.002). MRI(+)/pathology(+) had higher remission odds than MRI(-)/pathology(-) (OR 4.96, 95%CI 1.06-23.16, p=0.019). There were no significant differences in LNSC/DST/UFC levels. ACTH levels were higher in MRI(+)/pathology(+) (99.4 pg/mL) than MRI(+)/pathology(-) (41.6 pg/mL, p=0.017) and MRI(-)/pathology(-) (40.3 pg/mL, p=0.014). Using logistic regression analysis, only ACTH levels predicted remission (OR 1.03, 95%CI 1.01-1.05, p=0.008). Basal IPS:P in MRI(+)/pathology(+) was significantly higher than in MRI(+)/pathology(-) (9.4 vs. 3.5, p=0.022). Furthermore, basal IPS:P >2 was a significant predictor of remission (OR 3.65, p=0.019) but maximum IPS:P >3 was not (p=0.145). CONCLUSIONS Only preoperative ACTH levels and basal IPS:P >2 predicted surgical remission. These findings support refining preoperative endocrine evaluation and patient selection in Cushing’s disease.
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Himstead et al. (2025) studied this question.
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