Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-25T11:33:17.626Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinically Non-Functioning Human Pituitary Adenomas

Published online by Cambridge University Press:  18 September 2015

Sylvia L. Asa  and
Kalman Kovacs
Sylvia L. Asa*
Affiliation:
Department of Pathology, St. Michael’s Hospital, University of Toronto, Toronto
Kalman Kovacs
Affiliation:
Department of Pathology, St. Michael’s Hospital, University of Toronto, Toronto
*
Department of Pathology, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell adenomas. We suggest that null cell adenomas and oncocytomas originate in uncommitted pluripotent precursor cells capable of undergoing multidirectional differentiation. The progenitor cells differentiate most frequently toward FSH / a-subunit producing cells; the mechanism of preferential differentiation is obscure.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue 2 , May 1992 , pp. 228 - 235
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1.Kovacs, K, Horvath, E.Tumors of the Pituitary Gland. Fascicle 21, Second Series. Atlas of Tumor Pathology. Washington, D.C.: Armed Forces Institute of Pathology, 1986.Google Scholar
2.Kovacs, K, Lloyd, R, Horvath, E, et al. Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. Am J Pathol 1989; 134: 345–353.Google ScholarPubMed
3.Horvath, E, Kovacs, K, Smyth, HS, et al. A novel type of pituitary adenoma: morphological features and clinical correlations. J Clin Endocrinol Metab 1988; 66: 1111–1118.CrossRefGoogle ScholarPubMed
4.Kovacs, K, Horvath, E, Ryan, N, Ezrin, C.Null cell adenoma of the human pituitary. Virchows Arch [Pathol Anat] 1980; 387: 165–174.CrossRefGoogle ScholarPubMed
5.Yamada, S, Asa, SL, Kovacs, K.Oncocytomas and null cell adenomas of the human pituitary: morphometric and in vitro functional comparison. Virchows Arch [A] 1988; 413: 333–339.CrossRefGoogle ScholarPubMed
6.Asa, SL, Gerrie, BM, Singer, W, et al. Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas. J Clin Endocrinol Metab 1986; 62: 1011–1019.CrossRefGoogle ScholarPubMed
7.Jameson, JL, Klibanski, A, Black, PM, et al. Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. J Clin Invest 1987; 80: 1472–1478.CrossRefGoogle ScholarPubMed
8.Lloyd, RV, Jin, L, Fields, K, et al. Analysis of pituitary hormones and chromogranin A mRNAs in null cell adenomas, oncocytomas, and gonadotroph adenomas by in situ hybridization. Am J Pathol 1991; 139:553–564.Google ScholarPubMed
9.Sakurai, T, Seo, H, Yamamoto, N, et al. Detection of mRNA of prolactin and ACTH in clinically nonfunctioning pituitary adenomas. J Neurosurg 1988; 69: 653–659.CrossRefGoogle ScholarPubMed
10.Serri, O, Marchisio, AM, Collu, R, et al. Dopaminergic binding sites in human pituitary adenomas other than prolactinomas. Horm Res 1984; 19:97–100.CrossRefGoogle ScholarPubMed
11.Koga, M, Nakao, H, Arao, M, et al. Demonstration of specific dopamine receptors on human pituitary adenomas. Acta Endocrinol 1987; 144: 595–602.Google Scholar
12.Lloyd, RV, Anagnostou, D, Chandler, WF.Dopamine receptors in immunohistochemically characterized null cell adenomas and normal human pituitaries. Mod Pathol 1988; 1: 51–56.Google ScholarPubMed
13.Le Dafniet, M, Grouselle, D, Li, JY, et al. Evidence of thyrotropinreleasing hormone (TRH) and TRH-binding sites in human non-secreting pituitary adenomas. J Clin Endocrinol Metab 1987; 65: 1014–1019.CrossRefGoogle Scholar
14.Reubi, JC, Heitz, PU, Landolt, AM.Visualization of somatostatin receptors and correlation with immunoreactive growth hormone and prolactin in human pituitary adenomas: evidence for different tumor subclasses. J Clin Endocrinol Metab 1987; 65: 65–73.CrossRefGoogle ScholarPubMed
15.Levy, A, Lightman, SL.Effects of thyrotropin-releasing hormone and gonadotropin-releasing hormone on inositol phospholipid turnover in endocrinologically inactive pituitary adenomas and prolactinomas. J Clin Endocrinol Metab 1989; 69: 122–126.CrossRefGoogle ScholarPubMed
16.Spada, A, Reza-Elahi, F, Lania, A, Bassetti, M.Hypothalamic neuropeptide action in human non-secreting pituitary adenomas. J Endocrinol Invest 1990; 13: 25. (abst)Google Scholar
17.Klibanski, A.Nonsecreting pituitary tumors. Endocrinol Metab Clin North Am 1987; 16: 793–804.CrossRefGoogle ScholarPubMed
18.Asa, SL, Kovacs, K, Horvath, E, et al. Human fetal adenohypophysis. Electron microscopic and ultrastructural immunocytochemical analysis. Neuroendocrinology 1988; 48: 423–431.CrossRefGoogle ScholarPubMed
19.Lloyd, RV.Use of molecular probes in the study of endocrine diseases. Hum Pathol 1987; 18: 1199–1211.CrossRefGoogle Scholar
20.Asa, SL, Cheng, Z, Ramyar, L, et al. Human pituitary null cell adenomas and oncocytomas in vitro: effects of adenohypophysiotropic hormones and gonadal steroids on hormone secretion and tumor cell morphology. J Clin Endocrinol Metab 1992; (in Press).Google ScholarPubMed
21.Yamada, S, Asa, SL, Kovacs, K, Muller, P, Smyth, HS.Analysis of hormone secretion by clinically nonfunctioning human pituitary adenomas using the reverse hemolytic plaque assay. J Clin Endocrinol Metab 1989; 68: 73–80.CrossRefGoogle ScholarPubMed
22.Klibanski, A, Zervas, NT, Kovacs, K, Ridgway, EC.Clinically silent hypersecretion of growth hormone in patients with pituitary tumors. J Neurosurg 1987; 66: 806–811.CrossRefGoogle ScholarPubMed
23.Horvath, E, Kovacs, K, Killinger, DW, et al. Silent corticotropic adenomas of the human pituitary gland. A histologic, immunocytologic, and ultrastructural study. Am J Pathol 1980; 98: 617–638.Google ScholarPubMed
24.Hassoun, J, Charpin, C, Jaquet, P, et al. Corticolipotropin immunoreactivity in silent chromophobe adenomas. A light and electron microscopic study. Arch Pathol Lab Med 1982; 106: 25–30.Google ScholarPubMed
25.Reincke, M, Allolio, B, Saeger, W, Kaulen, D, Winkelmann, W.A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing’s disease. J Clin Endocrinol Metab 1987; 65: 1296–1300.CrossRefGoogle ScholarPubMed
26.Trouillas, J, Girod, C, Sassolas, G, et al. A human (3-endorphin pituitary adenoma. J Clin Endocrinol Metab 1984; 58: 242–249.CrossRefGoogle Scholar
27.Kovacs, K, Horvath, E, Bayley, TA, Hassaram, ST, Ezrin, C.Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity. Am J Med 1978; 64: 492–499.CrossRefGoogle ScholarPubMed
28.Lloyd, RV, Fields, K, Jim, L, Horvath, E, Kovacs, K.Analysis of endocrine active and clinically silent corticotropic adenomas by in situ hybridization. Am J Pathol 1990; 137: 479–488.Google ScholarPubMed
29.Stefaneanu, L, Kovacs, K, Horvath, E, Lloyd, RV.In situ hybridization study of pro-opiomelanocortin (POMC) gene expression in human pituitary corticotropin and their adenomas. Virchows Arch [Pathol Anat] 1991; 419: 107–113.CrossRefGoogle ScholarPubMed
30.Chabre, O, Martinie, M, Vivier, J, et al. A clinically silent corticotrophic pituitary adenoma (CSCPA) secreting a biologically inactive but immunoreactive assayable ACTH. J Endocrinol Invest 1991; 14 (Suppl 1): 87. (abst)Google Scholar
31.Trouillas, J, Girod, C, Sassolas, G, et al. Human pituitary gonadotropic adenoma; histological, immunocytochemical, and ultrastructural and hormonal studies in eight cases. J Pathol 1981; 135:315–336.CrossRefGoogle ScholarPubMed
32.Asa, SL, Gerrie, BM, Kovacs, K, et al. Structure-function correlations of human pituitary gonadotroph adenomas in vitro. Lab Invest 1988; 58:403–410.Google ScholarPubMed
33.Snyder, PJ.Gonadotroph cell adenomas of the pituitary. Endocrinol Rev 1985; 6: 552–563.Google ScholarPubMed
34.Daneshdoost, L, Gennarelli, TA, Bashey, HM, et al. Recognition of gonadotroph adenomas in women. N Engl J Med 1991; 324: 589–594.CrossRefGoogle ScholarPubMed
35.Snyder, PJ, Bashey, HM, Kim, SU, Chappel, SC.Secretion of uncombined subunits of luteinizing hormone by gonadotroph cell adenomas. J Clin Endocrinol Metab 1984; 59: 1169–1175.CrossRefGoogle ScholarPubMed
36.Klibanski, A, Deutsch, PJ, Jameson, JL, et al. Luteinizing hormonesecreting pituitary tumor: biosynthetic characterization and clinical studies. J Clin Endocrinol Metab 1987; 64: 536–542.CrossRefGoogle ScholarPubMed
37.Black, PM, Hsu, DW, Klibanski, A, et al. Hormone production in clinically nonfunctioning pituitary adenomas. J Neurosurg 1987; 66: 244–250.CrossRefGoogle ScholarPubMed
38.Surmont, DWA, Winslow, CLJ, Loizou, M, et al. Gonadotrophin and alpha subunit secretion by human ‘functionless’ pituitary adenomas in cell culture: long term effects of luteinizing hormone releasing hormone and thyrotrophin releasing hormone. Clin Endocrinol (Oxf) 1983; 19: 325–336.CrossRefGoogle ScholarPubMed
39.Kwekkeboom, DJ, de Jong, FH, Lamberts, SWJ.Gonadotrophin release by clinically nonfunctioning and gonadotroph pituitary adenomas in vivo and in vitro: relation to sex and effects of thyrotropin-releasing hormone, gonadotropin-releasing hormone, and bromocriptine. J Clin Endocrinol Metab 1989; 68: 1128–1135.Google ScholarPubMed
40.Kontogeorgos, G, Horvath, E, Kovacs, K, Killinger, DW, Smyth, HS.Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation. Arch Pathol Lab Med 1991; 115:61–64.Google ScholarPubMed
41.Horvath, E, Kovacs, K.Gonadotroph adenomas of the human pituitary: sex-related fine-structural dichotomy. A histologic, immunocytochemical, and electron-microscopic study of 30 tumors. Am J Pathol 1984; 117:429–440.Google ScholarPubMed
42.Kovacs, K, Asa, SL, Horvath, E, et al. Null cell adenomas of the pituitary: attempts to resolve their cytogenesis. In: Lechago, J, Kameya, T, eds. Endocrine Pathology Update. New York: Field and Wood 1990: 17–31.Google Scholar
43.Alexander, JM, Biller, BMK, Bikkal, H, et al. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 1990; 86: 336–340.CrossRefGoogle ScholarPubMed