Case Report

Mod Pathol 2002;15(10):1102–1105

A Case of Cushing's Disease Caused by Pituitary Adenoma Producing Adrenocorticotropic Hormone and Growth Hormone Concomitantly: Aberrant Expression of Transcription Factors NeuroD1 and Pit-1 as a Proposed Mechanism

Shigeyuki Tahara M.D., Ph.D.1, Reiko Kurotani Ph.D.2, Yudo Ishii M.D.1, Naoko Sanno M.D., Ph.D.1, Akira Teramoto M.D., Ph.D.1 and R. Yoshiyuki Osamura M.D., Ph.D.2

  1. 1Department of Neurosurgery, Nippon Medical School, Tokyo, Japan
  2. 2Department of Pathology, Tokai University School of Medicine, Boseidai, Isehara-city, Kanagawa, Japan

Correspondence: Robbert Yoshiyuki Osamura, Department of Pathology, Tokai University School of Medicine, Isehara-city, Kanagawa, 259-1193, Japan; e-mail: osamura@is.icc.u-tokai.ac.jp; fax: 81-463-91-1370.

Accepted 27 June 2002.

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Abstract

A 53-year-old Japanese woman was diagnosed with Cushing's disease caused by a adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the basis of clinical an imaging data. The surgically resected tumor tissue was investigated histopathologically using immunohistochemical analysis of pituitary hormones. Our study revealed that the adenoma expressed not only ACTH but growth hormone (GH) in the tumor cells. Furthermore, immunohistochemical double staining showed that some adenoma cells were positive for both ACTH and GH. In situ hybridization for GH mRNA revealed that the adenoma cells produced GH as opposed to simply storing it. Although many pituitary adenomas produce multiple pituitary hormones, pituitary adenoma producing both ACTH and GH in the same adenoma cells, such as seen in this case, is extremely rare. To elucidate the molecular mechanism involved, we investigated the expression of transcription factors NeuroD1 and Pit-1 and found that both transcription factors were expressed in many tumor cells. This case report describes a very rare case of pituitary adenoma that produced both ACTH and GH. We propose a hitherto undescribed translineage expression of transcription factors as the basic mechanism of this unique functional differentiation.

Keywords:

ACTH, ACTH-secreting adenoma, Cushing's disease, GH, NeuroD1, Pit-1, Pituitary, Transcription factor

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