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.
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.
Tahara
Shigeyuki
S
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Kurotani
Reiko
R
Ishii
Yudo
Y
Sanno
Naoko
N
Teramoto
Akira
A
Osamura
R Yoshiyuki
RY
D000236:Adenoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins; D003480:Cushing Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D015345:Oligonucleotide Probes / Q000737:chemistry; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D015534:Trans-Activators / Q000378:metabolism*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
D000324:Adrenocorticotropic Hormone; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C093970:NEUROD1 protein, human; C494187:POU1F1 protein, human