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

Kozo Hashimoto, Isao Nagano, Koichi Asaba, Mari Inoue, Tatsuya Nishioka, Toshihiro Takao, Takahito Nakajo, Takahisa Mori, Masahiro Kurisaka, Fumio Otsuka

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Background: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. Methods/Results: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing's disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing's disease. Magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient's residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly 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 pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor Il and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. Conclusion: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient's pituitary adenoma.

Original languageEnglish
Pages (from-to)198-202
Number of pages5
JournalHormone Research
Issue number4
Publication statusPublished - Dec 1 2000


  • Adrenocorticotropic hormone
  • Cushing's disease
  • Insulin-like growth factor II
  • MIB-1 antibody
  • Pituitary adenoma
  • Proliferating cell nuclear antigen

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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