"Silent"corticotropinoma.

OBJECTIVES: The aim of the study was to evaluate the ACTH-immunopositive pituitary adenomas, especially those without manifestation of Cushing's disease

MATERIAL AND METHODS: 148 pituitary adenomas removed surgically in years 1994--2007 were studied. The paraffin sections were immunostained with antibodies against the pituitary hormones. In 79 adenomas the immunostaining with anti-ACTH antibody was performed Additionally, 23 tumors were also immunostained with anti-Ki-67 (MIB-1) antibody. Visualization of reactions was done by means of streptavidin-biotin-peroxidase technique with use of 3,3'-diaminobenzidine as chromogen.

RESULTS: ACTH immunopositivity was found in 34 cases (23%). Fourteen ACTH-immunopositive tumors manifested themselves as Cushing's disease (including 1 case of Nelson's syndrome). In the remaining 20 cases in spite of the positive immunostaining for ACTH of the tumor cells, no features of hypercortisolism were observed (in several cases even hypocortisolism was found). Thus, those tumors represented so-called "silent" corticotropinomas. Over one third (37%) of "clinically" nonfunctioning pituitary adenomas, when immunostained with anti-ACTH antibody, showed ACTH immunopositivity. Three adenomas in patients with Cushing's disease (21.4%) and 7 "silent" corticotropinomas (35%) were recurrent tumors. In contrast, the recurrence rate in the group of ACTH-immunonegative clinically nonfunctioning pituitary adenomas was 14.7%. The "silent" corticotropinomas exhibited a tendency towards the higher expression of a proliferation marker, Ki-67 antigen as compared to the "active" corticotropinomas.

CONCLUSIONS: (i) "Silent" corticotropinomas are rather frequent. (ii) This adenoma type should be considered as aggressive. (iii) It is hypothetized that--like in Nelson's syndrome--the lack of hypercortisolism or even presence of hypocortisolism favorizes the exaggerated growth of tumoral corticotrophs.