Silent corticotroph adenomas: Further clinical and pathological observations

John A. Lopez, B. K. Kleinschmidt-Demasters, Chun I. Sze, Whitney W. Woodmansee, Kevin O. Lillehei

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48 Citations (Scopus)


Adrenocorticotroph cell pituitary adenomas immunoreactive for adrenocorticotropic hormone (ACTH) but unassociated with preoperative signs of hypercortisolism constitute between 6% and 43% of all ACTH adenomas. Few large series have been published. At our referral center for pituitary diseases, we have encountered 12 patients with silent ACTH adenomas, none of whom exhibited definite clinical features of hypercortisolism preoperatively. Two patients presented with apoplexy, and in 2 patients preoperative neuroimaging studies mimicked craniopharyngioma. Pathological examination revealed 8 adenomas with variably basophilic cytoplasm (type I, including 1 each with coarse basophilic granules and Crooke's hyaline change) and 4 with predominantly chromophobic cytoplasm (type II). Diffuse versus patchy (30% to 50% of cells) immunostaining best distinguished these 2 types; calcitonin staining was focal or negative in both. Two patients had unexpected postoperative courses consistent with acute cortisol insufficiency; 1 patient suffered from a severe flu-like illness, and the other had dizziness and was found to have a serum cortisol level of < 1.0 μg/dL. Both patients improved after cortisol replacement followed by a slow taper. Another patient developed 2 separate pituitary adenomas, a silent ACTH adenoma followed by a pure prolactinoma resected months later. Clonality studies demonstrated that the 2 tumors had arisen from different clonal populations. These cases offer additional insights into clinical, neuroimaging, histological, and biological features of silent ACTH adenomas. Because 2 of these patients seemed to require postoperative cortisol supplementation that otherwise would not have been given, clinicians should be notified about ACTH immunostaining in adenomas from patients without preoperative diagnoses of Cushing's disease, to optimize postoperative care.

Original languageEnglish
Pages (from-to)1137-1147
Number of pages11
JournalHuman Pathology
Issue number9
Publication statusPublished - 2004 Sep

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine


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