Corticotroph hyperplasia and Cushing disease: diagnostic features and surgical management

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  • 1 Department of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts;
  • 2 Department of Neurosurgery, University of North Carolina Hospitals, Chapel Hill, North Carolina;
  • 3 Department of Pathology, Brigham and Women’s Hospital/Harvard Medical School, Boston;
  • 4 Dana Farber Cancer Institute, Boston;
  • 5 Harvard TH Chan School of Public Health, Boston; and
  • 6 Division of Endocrinology, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts
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OBJECTIVE

This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes.

METHODS

Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups.

RESULTS

The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke’s hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7–7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4–2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups.

CONCLUSIONS

This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

ABBREVIATIONS ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; HPA = hypothalamic-pituitary-adrenal; HR = hazard ratio; IPSS = inferior petrosal sinus sampling; ROC = receiver operating characteristic; UFC = urinary free cortisol.

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Contributor Notes

Correspondence Michael P. Catalino: University of North Carolina Hospitals, Chapel Hill, NC. michael.catalino@unchealth.unc.edu.

INCLUDE WHEN CITING Published online September 4, 2020; DOI: 10.3171/2020.5.JNS201514.

Disclosures Dr. Min receives clinical or research support for the study described (includes equipment or material) from Corcept.

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