Abstract
BackgroundGlucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD.MethodsThe retrospective chart review study included patients with clinical, biochemical, radiologic and outcome data and evaluable histopathology specimens from pituitary surgery for CD. The main outcome was remission of CD, defined by clinical features, biochemical testing, and corticosteroid dependency.ResultsOf 144 CD patients, 60 (50 women, mean age 43.6±14) had clinical follow-up, biochemical data and histopathology specimens that included evaluable nontumorous adenohypophysis. Specimens from 50 patients (83.3%) demonstrated CC in nontumorous corticotrophs, and 10 (16.7%) had no CC (including 3 with corticotroph hyperplasia). One patient with CC was lost to follow-up and one without CC had equivocal outcome results. During a mean (SD) follow-up period of 74.9 months (61.0), recurrent or persistent disease was documented in 18 patients (31.0%), while 40 (69.0%) were in remission. In patients with CC, the remission rate was 73.5% (95% CI, 59.7%-83.7%) (36/49), whereas it was 44.4% (95% CI, 18.9%-73.3%) (4/9) in patients with no CC. The combination of serum cortisol >138 nmol/L within a week of surgery coupled with absence of nontumorous CC greatly improved the prediction of recurrent or persistent disease.ConclusionsCC of nontumorous corticotrophs was observed in 83% of patients with CD, and most patients with CC experienced remission. Absence of CC in nontumorous corticotrophs may serve as a predictor of reduced remission in patients with CD.
Highlights
Glucocorticoid excess leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of normal corticotrophs in the pituitary
In patients with Cushing disease (CD), this change may be seen in the nontumorous pituitary tissue in response to glucocorticoid excess resulting from an ACTH-producing pituitary corticotroph tumor [4,5,6,7]
Of 144 patients who had pituitary surgery for CD, 66 were excluded due to lack of a pathology sample that was reviewed by an expert pathologist or lack of complete clinical data, including biochemical and imaging studies to confirm the clinical diagnosis of CD or remission vs. recurrent/persistent disease
Summary
Glucocorticoid excess leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of normal corticotrophs in the pituitary. Crooke’s cells are corticotrophs with concentric cytoplasmic accumulation of cytokeratin filaments This accumulation of glassy, homogeneous, hyaline material in the cytoplasm leads to displacement of the secretory granules around the nucleus or at the periphery of the cytoplasm. Immunostaining for CAM5.2 can show strong reactivity of the Crooke's cells [1,2,3] (Figure 1) This change is identified in the pituitaries of patients with any source of glucocorticoid excess, including Cushing syndrome due to exogenous corticosteroids, adrenal cortical tumors, and ectopic ACTH syndrome. Glucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD
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