Absence of peritumoral Crooke's change is associated with recurrence in surgically treated Cushing's disease.
BACKGROUND
Pituitary surgery is the standard treatment for Cushing's disease but is complicated by a recurrence rate that ranges from 5.9 to 27%. Whereas some recurrences may be due to technical or anatomical factors resulting in subtotal resection of adenoma, clinical relapse after total tumor resection is a well-documented occurrence. The factors leading to such recurrences are unknown.


METHODS
With the hypothesis that the pathology of the nontumoral adenohypophysis is important in predicting relapse, we undertook a study to determine if the absence of Crooke's change (CC), thought to be an indicator of nontumoral corticotroph inhibition, was associated with unexpected clinical recurrence. Twenty-one patients with Cushing's disease, with gross total resection of intrasellar corticotroph microadenoma, were reviewed independently by 2 neuropathologists for the presence of CC in adjacent adenohypophysis. All tumors were stained with H&E, PAS/orange-G and immunohistochemistry for ACTH. Clinical relapse was determined by chart reviews and defined as serum ACTH > 15 pg/ml, clinically Cushingoid, and/or radiographic evidence of recurrent tumor.


RESULTS
Seven of 21 patients recurred; 3 did not have CC in their initial resection specimen. All 3 of these patients had unexpected recurrences at 6 to 48 months post-op. Two patients with CC recurred at one year follow-up, 1 after 4 years and 1 after 5 years. All specimens from patients with long-term cure (follow-up from 9-72 months) contained CC. In this study, the absence of CC in peritumoral adenohypophysis was associated with unexpected recurrence of Cushing's disease (p = 0.0214).


CONCLUSIONS
We conclude that absence of CC in peritumoral adenohypophysis may be of some assistance in predicting recurrence of Cushing's disease after adequate resection of intrasellar microadenoma.
Hague
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Department of Pathology, Mt. Sinai School of Medicine, New York, New York 10029, USA.
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Morgello
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D000236:Adenoma / Q000150:complications / Q000473:pathology* / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications / Q000473:pathology* / Q000601:surgery*; D012008:Recurrence; D012189:Retrospective Studies