Crooke's hyalinization in silent corticotroph adenoma: report of two cases.

Corticotroph adenomas rarely show Crooke's hyaline change in neoplastic cells, a feature similar to that of normal corticotroph cells exposed to excess cortisol. Crooke's cell adenomas are usually associated with Cushing's disease. Nonfunctioning examples are uncommon. We report two clinically silent corticotroph adenomas featuring extensive Crooke's hyalinization in neoplastic cells. The two patients were 49 and 59 yr of age and neither had Cushing's disease. Serum and urinary cortisol were normal. One patient had elevated serum adrenocorticotropic hormone. In our experience, the two patients accounted for 0.4% of pituitary adenomas operated on from January 1992 to December 2001 and 3.5% of all corticotroph adenomas. The two lesions had features of the subtype 1 silent corticotroph adenoma. Cytogenetic analysis performed on one lesion showed a normal karyotype (46;XY). Hyalinization in clinically silent Crooke's cell adenoma indicates that hyaline changes do not always relate to excess cortisol. It is known that neoplastic Crooke's cells show immunoreactivity for glucocorticoid receptors stronger than nontumorous Crooke's corticotrophs. This fact suggests that receptor overexpression or lack of receptor downregulation may result in hypersensitivity of neoplastic Crooke's cells to physiologic cortisol plasma levels.