Immunohistochemical properties of silent corticotroph adenoma and Cushing's disease.

Abstract

Proopiomelanocortin processing in corticotroph cells is known to be operated by prohormone convertase (PC) 1/3 which is activating several pro-proteins and prohormones by intracellular limited proteolysis processing. In this study, we hypothesized that PC1/3 expression differs between Cushing's disease (CD) and silent corticotroph adenoma (SCA), and investigated whether PC1/3 expression is involved in the adrenocorticotropin (ACTH) silence of SCA. We performed immunohistochemical analysis of pituitary adenoma specimens for six adenohypophysial hormones, PC1/3 and chromogranin A (CgA). Subjects for this study consisted of 12 anterior pituitary adenomas of CD (1 male, 11 female; 14-70 years old) and 31 non-functioning adenomas (23 male, 8 female; 32-71 years old).ACTH immunoreactivity was observed in all of CD and three of 31 non-functioning adenomas. The three cases diagnosed as SCA were also positive for growth hormone and follicle-stimulating hormone. Cushing's adenomas and SCAs were all positive for PC1/3. PC1/3-positive cells did not always colocalize with ACTH but some of them colocalized with CgA in SCAs. Even if PC1/3 is not present in corticotroph cells, PC1/3 immunoreactivity in SCA may originate from CgA-positive cells. We conclude that immunohistochemistry for PC1/3 is not helpful for differential diagnosis between CD and SCA in clinical practice, though the regulation of PC1/3 expression is likely to be an important etiological factor in ACTH silence of SCA. The diversity of immunohistochemical properties of SCA leads us to speculate that it is not a single entity and may be a general diagnostic term for adenomas of varying etiology.

• Authors: Kazumi Iino, Yutaka Oki, Fumie Matsushita, Miho Yamashita, Chiga Hayashi, Katsutoshi Miura, Shigeru Nishizawa, Hirotoshi Nakamura
• Journal: Pituitary (Pituitary) Vol. 10 Issue 1 Pg. 35-45 ( 2007) ISSN: 1386-341X [Print] United States
• PMID: 17410413 (Publication Type: Journal Article)

Chemical References

• Chromogranin A
• Human Growth Hormone
• Gonadotropin-Releasing Hormone
• Adrenocorticotropic Hormone
• Follicle Stimulating Hormone
• Thyrotropin
• Corticotropin-Releasing Hormone
• Growth Hormone-Releasing Hormone
• Proprotein Convertases

Topics

• Adenoma (metabolism)
• Adolescent
• Adrenocorticotropic Hormone (metabolism)
• Adult
• Aged
• Chromogranin A (blood)
• Corticotropin-Releasing Hormone
• Female
• Follicle Stimulating Hormone (metabolism)
• Gonadotropin-Releasing Hormone
• Growth Hormone-Releasing Hormone
• Human Growth Hormone (metabolism)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Pituitary ACTH Hypersecretion (metabolism)
• Pituitary Neoplasms (metabolism)
• Proprotein Convertases (blood)
• Thyrotropin