A spectrum of behaviour in silent corticotroph pituitary adenomas

Abstract

Silent corticotroph adenomas (SCA) are pituitary tumours positive on immunohistochemical staining for ACTH but without clinical evidence of Cushing's disease in the patient. Previous reports suggest that these tumours may behave in a more aggressive way then other pituitary adenomas. We have followed the natural history of SCA and assessed whether histopathological indices predict tumour behaviour. We identified 22 patients in whom trans-sphenoidal surgery was performed for a non-functioning adenoma (NFA) with positive immunostaining for ACTH between 1990 and 2000 and examined the history of their disease. Patients were followed up for a mean of 4.8 years. A total of 86.7% of patients had documented visual deficits at presentation. In four cases hypercortisolaemia was observed later in the course of the disease. Two patients died as a result of their SCA and 33.3% of tumours recurred. Recurrence was more frequent in patients treated with adjuvant radiotherapy. Pathological indices (increased mitotic range and Ki-67) did not predict recurrence or malignant transformation. We suggest that certain 'silent' corticotroph tumours may have the potential for ACTH secretion leading to hypercortisolaemia at a later stage in the disease. The possibility of transformation to a more aggressive tumour needs to be considered in all SCA.

Silent corticotroph adenomas

“…Notably, it has been shown that, in contrast to adenomas obtained from patients with Cushing's disease, which demonstrate strong positive prohormone convertase 1/3 (the enzyme involved in the post-translational processing of POMC into ACTH) immunoreactivity, silent corticotroph adenomas exhibit very weak expression (18). In surgical series, most tumours are macroadenomas with suprasellar extension present in 87-100% of the cases (5)(6)(7)(8). This is in contrast to Cushing's disease, which is mostly attributed to microadenomas (8).…”

“…This is in contrast to Cushing's disease, which is mostly attributed to microadenomas (8). Sphenoid or cavernous sinus invasion has been reported in 30-52% (5,7,8) and signs of haemorrhage, necrosis or cystic changes in 64% of the tumours (8). Notably, in a series of 23 cases of SCAs, there was no difference in the rates of invasion or apoplexy between subtypes 1 and 2 (8).…”

“…Notably, initial studies of classical markers of growth potential, such as mitotic count and nuclear expression of the proliferation-associated antigen Ki-67, showed no difference from functioning corticotroph adenomas (5,8). However, a more recent assessment of p53 oncoprotein expression and ploidy revealed a significantly higher presence of p53 and hypertetraploidy in SCAs than functioning corticotroph adenomas (20).…”

“…Thus, pre-operative tumour invasiveness, cavernous sinus extension, or dural invasion, tumour subtype, degree of ACTH immunoreactivity and Ki-67 index do not seem to be associated with increased risk of recurrence (5,7,19).…”

“…Acute or subacute pituitary apoplexy has been described in 9-41.7% (5-7). Other less commonly reported presenting clinical manifestations include loss of consciousness and nasal obstruction (5).…”