Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Pituitary
Published in: Pituitary 1/2007

01-03-2007

Immunohistochemical properties of silent corticotroph adenoma and Cushing’s disease

Authors: Kazumi Iino, Yutaka Oki, Fumie Matsushita, Miho Yamashita, Chiga Hayashi, Katsutoshi Miura, Shigeru Nishizawa, Hirotoshi Nakamura

Published in: Pituitary | Issue 1/2007

Login to get access

Abstract

Proopiomelanocortin processing in corticotroph cells is known to be operated by prohormone convertase (PC) 1/3 which is activating several proproteins 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.
Literature
1.
Seidah NG, Chretien M (1999) Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res 848:45–62PubMedCrossRef
2.
von Eggelkraut-Gottanka R, Beck-Sickinger AG (2004) Biosynthesis of peptide hormones derived from precursor sequences. Curr Med Chem 11:2651–2665
3.
Friedman TC, Loh YP, Birch NP (1994) In vitro processing of proopiomelanocortin by recombinant PC1 (SPC3). Endocrinology 135:854–862PubMedCrossRef
4.
Tanaka S (2003) Comparative aspects of intracellular proteolytic processing of peptide hormone precursors: studies of proopiomelanocortin processing. Zool Sci 20:1183–1198PubMedCrossRef
5.
Ohta S, Nishizawa S, Oki Y, Yokoyama T, Namba H (2002) Significance of absent prohormone convertase 1/3 in inducing clinically silent corticotroph pituitary adenoma of subtype I–immunohistochemical study. Pituitary 5:221–223PubMedCrossRef
6.
Sanno N, Teramoto A, Osamura RY, Horvath E, Kovacs K, Lloyd RV et al (2003) Pathology of pituitary tumors. Neurosurg Clin N Am 14:25–39, vi
7.
Tan EU, Ho MS, Rajasoorya CR (2000) Metamorphosis of a non-functioning pituitary adenoma to Cushing’s disease. Pituitary 3:117–122PubMedCrossRef
8.
Ambrosi B, Barbetta L, Dall’Asta C, Libe R (2001) Metamorphosis of a non-functioning pituitary adenoma to Cushing’s disease. Pituitary 4:127–128PubMedCrossRef
9.
Tanaka K, Shimizu N, Imura H, Fukata J, Hibi I, Tanaka T et al (1993) Human corticotropin-releasing hormone (hCRH) test: sex and age differences in plasma ACTH and cortisol responses and their reproducibility in healthy adults. Endocr J 40:571–579PubMed
10.
Kovacs K, Horvath E, Bayley TA, Hassaram ST, Ezrin C (1978) Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity. Am J Med 64:492–499PubMedCrossRef
11.
Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. Am J Pathol 98:617–638PubMed
12.
Horvath E, Kovacs K, Smyth HS, Killinger DW, Scheithauer BW, Randall R et al (1988) A novel type of pituitary adenoma: morphological features and clinical correlations. J Clin Endocrinol Metabol 66:1111–1118CrossRef
13.
Bradley KJ, Wass JA, Turner HE (2003) Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol (Oxf) 58:59–64CrossRef
14.
Lopez JA, Kleinschmidt-Demasters Bk B, Sze CI, Woodmansee WW, Lillehei KO (2004) Silent corticotroph adenomas: further clinical and pathological observations. Hum Pathol 35:1137–1147PubMedCrossRef
15.
Scheithauer BW, Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB et al (2000) Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery 47: 723–729; discussion 729–730
16.
Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER Jr (2003) Clinical characteristics of silent corticotrophic adenomas and creation of an internet-accessible database to facilitate their multi-institutional study. Neurosurgery 53: 1076–1084; discussion 1084–1075
17.
Vallette-Kasic S, Figarella-Branger D, Grino M, Pulichino AM, Dufour H, Grisoli F et al (2003) Differential regulation of proopiomelanocortin and pituitary-restricted transcription factor (TPIT), a new marker of normal and adenomatous human corticotrophs. J Clin Endocrinol Metabol 88:3050–3056CrossRef
18.
Scully KM, Rosenfeld MG (2002) Pituitary development: regulatory codes in mammalian organogenesis. Science 295:2231–2235PubMedCrossRef
19.
Tahara S, Kurotani R, Ishii Y, Sanno N, Teramoto A, Osamura RY (2002) 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. Mod Pathol 15:1102–1105PubMedCrossRef
20.
Osamura RY, Watanabe K (1988) Immunohistochemical studies of human FSH producing pituitary adenomas. Virchows Arch A Pathol Anat Histopathol 413:61–68PubMedCrossRef
21.
Kovacs K, Horvath E, Stefaneanu L, Bilbao J, Singer W, Muller PJ et al (1988) Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study. Case report. J Neurosurg 88:1111–1115
22.
Mazarakis N, Kontogeorgos G, Kovacs K, Horvath E, Borboli N, Piaditis G (2001) Composite somatotroph–ACTH-immunoreactive pituitary adenoma with transformation of hyperplasia to adenoma. Pituitary 4:215–221PubMedCrossRef
23.
Stefaneanu L, Kovacs K, Horvath E, Lloyd RV (1991) In situ hybridization study of pro-opiomelanocortin (POMC) gene expression in human pituitary corticotrophs and their adenomas. Virchows Arch A Pathol Anat Histopathol 419:107–113PubMedCrossRef
24.
Nagaya T, Seo H, Kuwayama A, Sakurai T, Tsukamoto N, Nakane T et al (1990) Pro-opiomelanocortin gene expression in silent corticotroph-cell adenoma and Cushing’s disease. J Neurosurg 72:262–267PubMed
25.
Matsuno A, Okazaki R, Oki Y, Nagashima T (2004) Secretion of high-molecular-weight adrenocorticotropic hormone from a pituitary adenoma in a patient without Cushing stigmata. Case report. J Neurosurg 101:874–877PubMedCrossRef
26.
Lloyd RV, Jin L, Qian X, Scheithauer BW, Young WF Jr, Davis DH (1995) Analysis of the chromogranin A post-translational cleavage product pancreastatin and the prohormone convertases PC2 and PC3 in normal and neoplastic human pituitaries. Am J Pathol 146:1188–1198PubMed
27.
Takumi I, Steiner DF, Sanno N, Teramoto A, Osamura RY (1998) Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy. Mod Pathol 11:232–238PubMed
28.
Jin L, Kulig E, Qian X, Scheithauer BW, Young WF Jr, Davis DH et al (1999) Distribution and regulation of proconvertases PC1 and PC2 in human pituitary adenomas. Pituitary 1:187–195PubMedCrossRef
29.
Uehara M, Yaoi Y, Suzuki M, Takata K, Tanaka S (2001) Differential localization of prohormone convertases PC1 and PC2 in two distinct types of secretory granules in rat pituitary gonadotrophs. Cell Tissue Res 304:43–49PubMedCrossRef
30.
Kato H, Kuwako K, Suzuki M, Tanaka S (2004) Gene expression patterns of pro-opiomelanocortin-processing enzymes PC1 and PC2 during postnatal development of rat corticotrophs. J Histochem Cytochem 52:943–957PubMedCrossRef
31.
Lloyd RV, Scheithauer BW, Kovacs K, Roche PC (1996) The Immunophenotype of Pituitary Adenomas. Endocr Pathol 7:145–150PubMed
32.
Heaney AP, Curry WJ, Pogue KM, Armstrong VL, Mirakhur M, Sheridan B et al (2000) Immunohistochemical evaluation of the post-translational processing of chromogranin A in human pituitary adenomas. Pituitary 3:67–75PubMedCrossRef
33.
Pawlikowski M, Gruszka A, Radek M, Kunert-Radek J (2004) Chromogranin A in pituitary adenomas: immunohistochemical detection and plasma concentrations. Folia Histochem Cytobiol 42:245–247PubMed
Metadata
Title
Immunohistochemical properties of silent corticotroph adenoma and Cushing’s disease
Authors
Kazumi Iino
Yutaka Oki
Fumie Matsushita
Miho Yamashita
Chiga Hayashi
Katsutoshi Miura
Shigeru Nishizawa
Hirotoshi Nakamura
Publication date
01-03-2007
Published in
Pituitary / Issue 1/2007
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-007-0010-5

Other articles of this Issue 1/2007

Pituitary 1/2007 Go to the issue

Case Report

Lymphocytic panhypophysitis in a young man with involvement of the cavernous sinus and clivus

OriginalPaper

Treatment of acromegaly: is there still a place for radiotherapy?

Case Report

Fatal inflammatory hypophysitis

ReviewPaper

Anterior pituitary hormone replacement therapy—a clinical review

OriginalPaper

Efficacy and safety of CyberKnife radiosurgery for acromegaly

OriginalPaper

Decreased ghrelin-induced GH release in thyrotoxicosis: comparison with GH-releasing peptide-6 (GHRP-6) and GHRH
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits