Clinical Presentations and Intraoperative Pathology Strategy in Cushing’s Disease

Abstract

Abstract 1 Background: To define the symptoms, signs and treatment outcomes in a population of older patients with Cushing’s disease (CD). Methods: We analyzed the clinical presentation and treatment outcomes in 45 CD patients older than 60 years, in comparison to 90 CD patients younger than 60, and a control group of 45 older patients with nonfunctioning pituitary adenomas. We reviewed preoperative clinical characteristics, medical comorbidities, imaging findings and endocrine testing as well as surgical and endocrine outcomes. Results: Older CD patients had significantly lower body mass index (BMI) (p = 0.031), were more likely to have muscle wasting (p = 0.006) and women were less likely to have hirsutism (p = 0.033). Older patients with CD had more medical comorbidities than younger patients, which correlated with a higher ASA grade (p < 0.001), but the surgical complication rates were similar in both groups. Surgical remission was achieved in 38/45 (84.4%) older patients and 78/90 (86.7%) younger patients (p = NS). Recurrent disease was more frequent in younger patients (19.2%) in comparison to older patients (2.6%, p = 0.019). Conclusions: Older patients with CD appear to have a distinct phenotype with a more catabolic picture, including a lower BMI and greater prevalence of muscle wasting. Surgical outcomes are similar without a significant age-related increase in complications. Abstract 2 Background: Cushing’s disease (CD) is most commonly caused by microadenomas, which at surgical exploration may not provide adequate tissue for pathologic diagnosis using standard techniques. We wished to determine the accuracy of intraoperative pathologic examination and whether the addition of intraoperative cytology increased the diagnostic yield. Methods: We reviewed the pathology reports from 403 operations on 341 patients with CD microadenomas from a single institution. The concordance rates of intraoperative diagnoses (cytology and frozen) with the final (paraffin section) pathological diagnosis was calculated. The overall pathologic confirmation of an adenoma (by either cytology, frozen or paraffin section) was compared with the result from a historical cohort (only using standard frozen section procedures but not intraoperative cytology) and the pooled results from a meta-analysis of previously published data. Results: The concordance rate between frozen section diagnosis and paraffin section histology was 390/403(96.8%), and the discordance rate was 13/403(3.2%). Intraoperative smears were prepared by the surgeon in 246 operations with an ambiguous or a minute tumor, when the surgeon suspected that there would be insufficient tissue for traditional frozen section and paraffin diagnosis. The concordance rate between cytological smear and paraffin section histology was 213/246(86.6%), and the discordance rate was 33/246(13.4%). In 54 cases (13.4%) with ultimate remission, pathologic confirmation was obtained only on intraoperative pathology (frozen section or cytology). Overall, pathologic confirmation was obtained in 326 operations (80.9%) by at least one pathological modality. The overall pathological confirmation rate of an adenoma was greater after the introduction of intraoperative cytology when compared to the historical control (67.1%, p = 0.015), and compared to the pooled rate of published data from the meta-analysis (72.1%, p < 0.001). Conclusion: Our findings suggest that intraoperative frozen and cytological section analyses during surgery for CD may be additional useful diagnostic tools for both neurosurgeons and neuropathologists.