Significant gene expression of insulin-like growth factor II and proliferating cell nuclear antigen in a rapidly growing recurrent pituitary ACTH-secreting adenoma

Background: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurre d very rapidly as invasive macroadenoma. Methods/Results: A 43-year-old wom an underwent successful transsphenoidal surgery for Gushing's disease. Seve n years later, she was admitted to our ward for further endocrine examinati ons. In spite of a very high plasma ACTH level, the serum cortisol level wa s normal. Discrepancies between ACTH and cortisol levels were detected on t he basis of diurnal rhythms, dexamethasone suppression tests, and corticotr opin-releasing hormone test. The patient showed no clinical features of Gus hing's disease. Magnetic resonance imaging of the pituitary showed an almos t empty sella, and no microadenoma was found. These results, along with tho se of Sephadex column gel filtration and high-performance liquid chromatogr aphy of plasma-immunoreactive ACTH, suggested that the patient's residual c orticotrophs secreted biologically inactive ACTH. Two years later, the pati ent suddenly developed diplopia and right abducens nerve palsy. She was sli ghtly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. Magnetic resonance imaging revealed a large pituit ary mass with suprasellar and cavernous sinus extensions. The tumor was exc ised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region o f the proopiomelanocortin gene. A significant expression of insulin-like gr owth factor II and proliferating cell nuclear antigen mRNAs was demonstrate d. A high MIB-1 antibody labeling index was also detected in the adenoma ti ssue, suggesting high Ki-67 expression. Conclusion: These growth- and proli feration-related factors might be involved in the rapid growth and aggressi veness of this patient's pituitary adenoma. Copyright (C) 2001 S.Karger AG, Basel.