The Classification and Molecular Biology of Pituitary Adenomas

  • K. Thapar
  • K. Kovacs
  • E. R. Laws
Part of the Advances and Technical Standards in Neurosurgery book series (NEUROSURGERY, volume 22)


As illustrated throughout this volume, the contemporary management of pituitary tumors has been the collective product of decades of multidisciplinary contribution. Innovation has been especially brisk during the past two decades in which the introduction of highly sensitive hormone assays, superior resolution imaging technology, trans-sphenoidal microsurgery, receptormediated pharmacotherapy, and focused beam radiotherapy have ushered in a promising new era in the diagnosis and therapy of pituitary tumors. Collectively, these contributions from many disciplines have rendered pituitary tumors eminently treatable, with many patients enjoying long term survival or cure.


Pituitary Adenoma Pituitary Tumor Cell Adenoma Pituitary Carcinoma Human Pituitary Adenoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alexander JM, Biller BMK, Bikkai H, Zervas NT, Arnold A, Klibanski A (1990) Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 86: 336–340PubMedCrossRefGoogle Scholar
  2. 2.
    Alvaro V, Touraine P, Raisman Vozarì R, Bai-Grenier F, Birrrian P, Joubert (Bression) D (1992) Protein kinase C activity and expression in normal and adenomatous human pituitaries. Int J Cancer 50: 724–730PubMedCrossRefGoogle Scholar
  3. 3.
    Alvaro V, Levy L, Deburay C, Roche A, Peillon F, Querat B, Joubert D (1993) Invasive human pituitary tumors express a point mutated alpha-protein kinase-C. J Clin Endocrinol Metab 77: 1125–1139PubMedCrossRefGoogle Scholar
  4. 4.
    Anniko M, Tribukait B, Wersall J (1984) DNA ploidy and cell phase in human pituitary tumors. Cancer 53: 1708–1713PubMedCrossRefGoogle Scholar
  5. 5.
    Asa SL, Ryan N, Kovacs K, Singer W Matangos PJ (1988) Immunohisto-chemical localization of neuron-specific enolase in the human hypophysis and pituitary adenomas. Arch Pathol Lab Med 112: 801–804Google Scholar
  6. 6.
    Asa SL, Kovacs K, Stefaneanu L, Horvath E, Billestrup N, Gonzales-Manchon C (1990) Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone, Proc Soc Exper Biol Med 193: 232–235Google Scholar
  7. 7.
    Asa SL, Kovacs K (1992a) Clinically nonfunctioning human pituitary adenomas. Can J Neurol Sci 19: 228–235PubMedGoogle Scholar
  8. 8.
    Asa SL, Kovacs K (1992b) Pituitary pathology in acromegaly. Endocrin Metab Clin North Am 21: 553–574Google Scholar
  9. 9.
    Asa SL, Cheng Z, Ranyar L, Singer W, Kovacs K, Smyth HS, Muller P (1992c) Human pituitary null cell adenomas and oncocytomas in vitro: effects of adenohypophysiotropic hormone and gonadal steroids on hormone secretion and tumor cell morphology. J Clin Endocrinol Metab 74: 1128–1134PubMedCrossRefGoogle Scholar
  10. 10.
    Asa SL, Puy LA, Lew AM, Sundmark VC, Elsholtz HP (1993) Cell type-specific expression of the pituitary transcription activator Pit-1 in the human pituitary and pituitary adenomas. J Clin Endocrinol Metab 77: 1275–1280PubMedCrossRefGoogle Scholar
  11. 11.
    Atkin SL, Landolt AM, Jeffereys RV, Divewr M, Radcliff J, White MC (1993) Basic fibroblastic growth factor stimulated prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation. J Clin Endocrinol Metab 77: 831–837PubMedCrossRefGoogle Scholar
  12. 12.
    Barkan AL (1992) Acromegaly. Trends Endocrinol Metab 3: 205–2192PubMedCrossRefGoogle Scholar
  13. 13.
    Barrett JC (1991) Molecular mechanisms of hormonal carcinogenesis. In: Li JJ, Nandi S, Li SA (eds) Hormonal carcinogenesis. Springer, Berlin Heidelberg New York Tokyo, pp 159–163Google Scholar
  14. 14.
    Biller BMK, Alexander JM, Zervas NT, Hedley-White ET, Arnold A, Klibanski A (1992) Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing’s disease. J Clin Endocrinol Metab 75: 1303–1309PubMedCrossRefGoogle Scholar
  15. 15.
    Billestrup N, Swanson LW, Vale W (1986) Growth hormone-releasing factor stimulated proliferation of somatotrophs in vitro. Proc Natl Acad Sci USA 83: 6854–6857PubMedCrossRefGoogle Scholar
  16. 16.
    Billestrup N, Mitchell RL, Vale W, Varma IM (1987) Growth hormone releasing factor induces c-fos expression in cultured primary pituitary cells. Mol Endocr 1: 300–305CrossRefGoogle Scholar
  17. 17.
    Birman P, Michard M, Li Y, Peillon F, Bresion D (1987) Epidermal growth factor-binding sites, present in normal human and rat pituitaries are absent in human 18 pituitary adenomas. J Clin Endocrinol Metab 65: 275–281PubMedCrossRefGoogle Scholar
  18. 18.
    Black EG, Logan A, Davis JRF, Sheppard MC (1990) Basic fibroblastic growth factor affects DNA synthesis and cell function and activates multiple signalling pathways in rat thyroid FRTL-5 and pituitary GH3 cells. J Endocrinol 127: 39–46PubMedCrossRefGoogle Scholar
  19. 19.
    Bodner M, Karin (1987) A pituitary-specific trans-acting factor can stimulate transcription from the growth hormone promoter in extracts of non-expressing cells. Cell 50: 267–275PubMedCrossRefGoogle Scholar
  20. 20.
    Burrow GN, Wortzman G, Rewcastle NB, Holgate RC, Kovacs K (1981) Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N Engl J Med 304: 156–158PubMedCrossRefGoogle Scholar
  21. 21.
    Burton FH, Hasel KW, Bloom FE, Sutcliff JG (1991) Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Nature 350: 74–77PubMedCrossRefGoogle Scholar
  22. 22.
    Bystrom C, Larsson C, Blomberg C, et al (1990) Localization of the MEN1 gene to a small region within chromosome llql3 by deletion mapping tumors. Proc Natl Acad Sci USA 87: 1968–1972PubMedCrossRefGoogle Scholar
  23. 23.
    Capra E, Rindi G, Pompei Spina M, Scappaticci S (1993) Chromosome abnormalities in a case of pituitary adenoma. Cancer Genet Cytogenet 68:140–142PubMedCrossRefGoogle Scholar
  24. 24.
    Castrillo JL, Theill LE, Karin M (1991) Function of the homeodomain protein GHF-1 in pituitary cell proliferation. Science 253: 197–199PubMedCrossRefGoogle Scholar
  25. 25.
    Cooper PR (1990) Nonoperative management of prolactin-secreting pituitary adenomas. In: Cooper PR (ed) Contemporary diagnosis and management of pituitary adenomas. American Association of Neurological Surgeons, Park Ridge, pp 83–100Google Scholar
  26. 26.
    Cramer W, Horning ES (1936) Experimental production of oestrin of pituitary tumors with hypopituitarism. Lancet 1: 247–249CrossRefGoogle Scholar
  27. 27.
    Cryns VL, Alexander JP, Klibanski A, Arnold A (1993) The retinoblastoma gene in human pituitary tumors. J Clin Endocrinol Metab 77: 644–646PubMedCrossRefGoogle Scholar
  28. 28.
    Ezzat S, Melmed S (1990) The role of growth factors in the pituitary. J Clin Endocrinol Metab 13: 691–698Google Scholar
  29. 29.
    Fitzgibbons PL, Appley AJ, Turner RR, Bishop PC, Parker JW, Breeze RE, Weiss MH, Apuzzo MLJ (1988) Flow cytometric analysis of pituitary tumors: correlations of nuclear antigen p105 and DNA content with clinical behavior. Cancer 62: 1556–1560PubMedCrossRefGoogle Scholar
  30. 30.
    Friend KE, Chiou YK, Laws ER Jr, Lopes MBS, Shupnik (1993) Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas. J Clin Endocrinol Metab 77: 1281–1286PubMedCrossRefGoogle Scholar
  31. 31.
    Furth J, Ueda G, Clifton KH (1973) The pathophysiology of pituitaries an d their tumors: methodological advances. In: Busch H (ed) Methods in cancer research, vol 10. Academic Press, New York, pp 201–277Google Scholar
  32. 32.
    Gerdes J, Lemke H, Baisch H, et al (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1470–1715Google Scholar
  33. 33.
    Gescher A (1992) Towards selective pharmacological modulation of protein kinase C-opportunities for the development of novel antineoplastic agents. Br J Cancer 66: 10–19PubMedCrossRefGoogle Scholar
  34. 34.
    Gesundheit N, Petrick PA, Nissim M, Dahlberg PA, Doppman JL, Emerson GH, Braverman LF, Oldfield (1989) Thyrotropin-secreting pituitary adenomas. Clinical and biochemical heterogeneity. Case reports and follow-up of nine patients. Ann Intern Med 111: 827–835PubMedGoogle Scholar
  35. 35.
    Gharib SD, Weirman MF, Shupnik MA, Chin WW (1990) Molecular biology of pituitary gonadotropins. Endocr Rev 11: 177–199PubMedCrossRefGoogle Scholar
  36. 36.
    Girod C, Trouillas J, Claustrat B (1986) The human thyrotropic adenoma: pathologic diagnosis in five cases and critical review of the literature. Semin Diagn Pathol 3: 58–68PubMedGoogle Scholar
  37. 37.
    Gonsky R, Herman V, Melmed S, Fagin J (1991) Transforming DNA sequences present in human prolactin-secreting tumors. Mol Endocrinol 5: 1687–1695PubMedCrossRefGoogle Scholar
  38. 38.
    Gospodarowicz D, Ferrera N, Schweigerer L, Neufeld G (1987) Structural characterisation and biological functions of fibroblastic growth factor. Endocr Rev 8: 95–111PubMedCrossRefGoogle Scholar
  39. 39.
    Hamilton CRJ, Adams LC, Maloof F (1970) Hyperthyroidism due to thyrotro-pin-producing pituitary chromophobe adenoma. N Engl J Med 283: 1077–1080PubMedCrossRefGoogle Scholar
  40. 40.
    Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor suppressor gene. N Engl J Med 329: 1318–1327PubMedCrossRefGoogle Scholar
  41. 41.
    Herman V, Drasin NZ, Gonsky R, Melmed S (1993) Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab 77: 50–55PubMedCrossRefGoogle Scholar
  42. 42.
    Herman V, Fagan J, Gonsky R, Kovacs K, Melmed S (1990) J Clin Endocrinol Metab 71: 1427–1433PubMedCrossRefGoogle Scholar
  43. 43.
    Hill SA, Falko JM, Wilson CB, Hunt WE (1982) Thyrotropin-producing pituitary adenomas. J Neurosurg 57: 515–519PubMedCrossRefGoogle Scholar
  44. 44.
    Horvath E, Kovacs K (1991) The adenohypophysis. In: Kovacs K, Asa SL (eds) Functional endocrine pathology. Blackwell, Boston, pp 245–281Google Scholar
  45. 45.
    Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotroph adenomas of the human pituitary gland: a histologic, immunocytologic and ultrastructural study. Am J Pathol 98: 617–638PubMedGoogle Scholar
  46. 46.
    Horvath E, Kovacs K, Smyth HS, Killinger DW, Schiethauer BW, Randall R, et al (1988) A novel type of pituitary adenoma: morphological features and clinical correlations. J Clin Endocrinol Metab 66: 1111–1118PubMedCrossRefGoogle Scholar
  47. 47.
    Hsu DW, Hakim F, Biller BMK, de La Monte S, Zervas NT, Klibanski A, Hedley-White ET (1993) Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg 78: 753–761PubMedCrossRefGoogle Scholar
  48. 48.
    Hsu DW, Raskind PN, Hedley-White TE (1989) Vasoactive intestinal peptide in the human pituitary gland and adenomas. Am J Pathol 135: 329–338PubMedGoogle Scholar
  49. 49.
    Ironside IW, Royds JA, Jefferson AA, Timperley WR (1987) Immunlocalization of cytokeratins in the normal and neoplastic human pituitary gland. J Neurol Neurosurg Psychiatry 50: 57–65PubMedCrossRefGoogle Scholar
  50. 50.
    Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359: 295–299PubMedCrossRefGoogle Scholar
  51. 51.
    Jacoby LB, Hedley-White ET, Pulaski K, Seizinger BR, Martuza RL (1990) Clonal origin of pituitary adenomas. J Neurosurg 73: 1427–1433Google Scholar
  52. 52.
    Jameson JL, Klibanski, Black PM, Zervas NT, Lindell CM, Hsu DW, Ridgeway EC, Habner JF (1987) Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. J Clin Invest 80: 1472–1478PubMedCrossRefGoogle Scholar
  53. 53.
    Joensuu H, Klemi PJ (1988) DNA aneurploidy in adenomas of endocrine organs. Am J Pathol 132: 145–151PubMedGoogle Scholar
  54. 54.
    Karga HJ, Alexander JM, Hedley-White ET, Klibanski A, Jameson JL (1992) Ras mutations in human pituitary tumors. J Clin Endocrinol Metab 74: 914–919PubMedCrossRefGoogle Scholar
  55. 55.
    Klibanski A, Zervas N (1991) Diagnosis and management of hormone-secreting pituitary adenomas. N Engl J Med 324: 822–831PubMedCrossRefGoogle Scholar
  56. 56.
    Knosp E, Kitz K, Perneczky A (1989) Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery 25: 927–930PubMedCrossRefGoogle Scholar
  57. 57.
    Kovacs K, Horvath E, Thorner MO, et al (1984) Mammosomatotroph hyperplasia associated with acromegaly and hyperprolactinemia in a patient with the McCuneAlbright syndrome. Virchows Arch (A) 403: 77–81CrossRefGoogle Scholar
  58. 58.
    Kovacs K, Horvath E (1986) Tumors of the pituitary gland. In: Atlas of tumor pathology, Fascicle 21, 2nd Series. Armed Forces Institute of Pathology, Washington, pp 1–269Google Scholar
  59. 59.
    Kovacs K (1988) Pathology of growth hormone excess. Pathol Res Pract 183: 565–568PubMedGoogle Scholar
  60. 60.
    Kovacs K, Horvath E, Asa SL, Stefaneanu L, Sano T (1989) Pituitary cells producing more than one homone. Human pituitary adenomas. Trends Endocr Metab 1: 104–107CrossRefGoogle Scholar
  61. 61.
    Kovacs K, Ryan N, Stefaneanu L (1987) Identification of corticotrophs in the human pituitary with mAB lu5, a novel immunocytochemical marker. Pathol Res Pract 182: 775–779PubMedGoogle Scholar
  62. 62.
    Kovacs K, Asa SL, Horvath E, Ryan N, Singer W, Killinger DW, Smyth HS, Scheithauer BW, Ebersold MJ (1990) Null cell adenomas of the pituitary: attempts to resolve their cytogenesis. In: Leschago J, Kameya T (eds) Endocrine pathology update. Field and Wood, New York, pp 17–31Google Scholar
  63. 63.
    Kovacs K, Stefaneanu L, Ezzat S, et al (1994) Prolactin producing pituitary adenoma in a male to female transsexual patient following protracted estrogen administration: a morphologic study. Arch Pathol Lab Med 118: 562–565PubMedGoogle Scholar
  64. 64.
    Landis C, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L (1989) GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenyl cyclase in human pituitary tumors. Nature 340: 692–696PubMedCrossRefGoogle Scholar
  65. 65.
    Landis CA, Harsh G, Lyons J, Davis RL, McCormick F, Bourne HR (1990) Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. J Clin Endocrinol Metab 71: 1416–1420PubMedCrossRefGoogle Scholar
  66. 66.
    Landolt AM, Schibata (1991) Growth, cell proliferation, and prognosis of pituitary adenomas. In: Faglia G, Beck-Peccoz P, Ambrosi B, Travagline P, Spada A (eds) Pituitary adenomas: new trends in basic and clinical research. Elsevier, Amsterdam, pp 169–178Google Scholar
  67. 67.
    Larsson C, Skogseid B, oberg K, Nakamura Y, Nordenskjold M (1988) Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332: 85–87PubMedCrossRefGoogle Scholar
  68. 68.
    LeRoith D, Clemmons D, Nissley P, Rechler MM (1992) Insulin-like growth factors in health and disease. Ann Int Med 116: 854–862PubMedGoogle Scholar
  69. 69.
    Levine AJ (1993) The tumor suppressor genes. Ann Rev Biochem 62: 623–651PubMedCrossRefGoogle Scholar
  70. 70.
    Ley A, Lightman SL (1992) Growth hormone releasing hormone transcripts in human pituitary adenomas. J Clin Endocrinol Metab 74: 1474–1476CrossRefGoogle Scholar
  71. 71.
    Li Y, Koga M, Kasayama S, et al (1992) Identification and characterization of high molecular weight forms of basic fibroblastic growth factor in human pituitary adenomas. J Clin Endocrinol Metab 75: 1436–1441PubMedCrossRefGoogle Scholar
  72. 72.
    Lloyd RV, Jin L, Chandler WF, Horvath E, Stefaneanu L, Kovacs K (1994) Pituitary specific transcription factor messenger RNA expression in adenomatous and nontumorous human pituitary tissues. Lab Invest 69:570–575Google Scholar
  73. 73.
    Lloyd RV, Wilson BS, Kovacs K, Ryan N (1985) Immunohistochemical localization of chromogranin in human hypophyses and pituitary adenomas. Arch Pathol Lab Med 109: 515–547PubMedGoogle Scholar
  74. 74.
    Marin F, Kovacs K, Stefaneanu L, Horvath E, Cheng Z (1992) S-100 protein immunopositivity in human nontumorous hypophyses and pituitary adenomas. Endocr Pathol 3: 28–38CrossRefGoogle Scholar
  75. 75.
    Marin F, Cheng Z, Kovacs K (1993) Ubiquitin immunoreactivity in corticotrophs following glucocorticoid treatment and in pituitary adenomase. Arch Pathol Lab Med 117: 254–258PubMedGoogle Scholar
  76. 76.
    McComb DJ, Ryan N, Horvath E, Kovacs K (1983) Sublinical adenomas of the human pituitary. New light on old problems. Arch Pathol Lab Med 107: 488–491PubMedGoogle Scholar
  77. 77.
    McCutcheon IE, Weintraub BD, Oldfield EH (1990) Surgical treatment of thyrotropin-secreting pituitary adenomas. J Neurosurg 73: 674–683PubMedCrossRefGoogle Scholar
  78. 78.
    Melmed S (1992) Etiology of pituitary acromegaly. Endocrinol Metab Clin North Am 21: 539–551PubMedGoogle Scholar
  79. 79.
    Melmed S, Braunstein GD, Change RJ, et al (1986) Pituitary tumors secreting growth hormone and prolactin. Ann Intern Med 105: 238–253PubMedGoogle Scholar
  80. 80.
    Mork SJ, Laerum OM (1980) Modal DNA content of human intracranial neoplasms studied by flow cytometry. J Neurosurg 53: 198–204PubMedCrossRefGoogle Scholar
  81. 81.
    Mormede P, Baird A (1988) Estrogens, cyclic adenosine 3′,5′-monophosphate and phorbol esters modulate the prolactin response of GH3 cells. J Endocrinol 127: 39–46Google Scholar
  82. 82.
    Mountcastle RB, Roof BS, Mayfield RK, Mordes DB, Sagel J, Biggs PJ, Rawe SE (1989) Case report: pituitary adenocarcinoma in an acromegalic patient. Response to bromocriptine and pituitary testing: a review of the literature on 36 cases of pituitary carcinoma. Am J Med Sci 298: 109–118PubMedCrossRefGoogle Scholar
  83. 83.
    Nagashima T, Murovic JA, Hoshino T, Wilson CB, DeArmond SJ (1986) The proliferative potential of human pituitary tumors in situ. J Neurosurg 64:588–593PubMedCrossRefGoogle Scholar
  84. 84.
    Nyquist P, Laws ER jr, Elliot E (1994) Novel features of tumors that secrete both growth hormone and prolactin in acromegaly. Neurosurgery 35: 179–184PubMedCrossRefGoogle Scholar
  85. 85.
    Pernicone PJ, Scheithauer BW (1993) Invasive pituitary adenomas and pituitary carcinomas. In: Lloyd RV (ed) Surgical pathology of the pituitary gland. Saunders, Philadelphia, pp 121–136Google Scholar
  86. 86.
    Pichon MF, Bression D, Peillon F, et al (1980) Estrogen receptors in human pituitary adenomas. J Clin Endocrinol Metab 51: 897–902PubMedCrossRefGoogle Scholar
  87. 87.
    Pietenpol JA, Holt JT, Stein RW, Moses HL (1990) Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of ketatinocyte proliferation. Proc Natl Acad Sci USA 87: 3758–3762PubMedCrossRefGoogle Scholar
  88. 88.
    Prager D. Melmed S, Fagin J (1989) Feedback regulation of growth hormone gene expression by insulin-like growth factor 1. In: LeRoith D, Raizada MK (eds) Molecular and cellular biology of insulin-like growth factors and their receptors. Plenum, New York, pp 57–68Google Scholar
  89. 89.
    Prager D, Melmed S (1993) Molecular pathology of sporadic pitutiary tumors. Endocr Pathol 4: 175–177CrossRefGoogle Scholar
  90. 90.
    Ramsdell IS (1991) Transforming growth factor-α and -β are are potent and effective inhibitors of GH4 pituitary tumor cell proliferation. Endcocrinology 128: 1981–1990CrossRefGoogle Scholar
  91. 91.
    Reichlin S (1991) Functional aspects of endocrine neoplasms. In: Kovacs K, Asa SL (eds) Functional endocrine pathology, vol 2. Blackwell, Boston, pp 898–913Google Scholar
  92. 92.
    Roberts V, Meunier H, Vaughan J, Rivier J, Rivier C, Vale W, Sawchenko P (1989) Regulation and regulation of inhibin subunits in pituitary gonadotropes. Endocrinology 124: 552–554PubMedCrossRefGoogle Scholar
  93. 93.
    Rock JP, Babu VR, Drumheller T, Chason J (1993) Cytogenetic findings in pituitary adenomas: results of a pilot study. Surg Neurol 40: 224–229PubMedCrossRefGoogle Scholar
  94. 94.
    Saeger W, Ludecke DK (1982) Pituitary adenomas with hyperfunction of TSH: frequency, histological classification, immunocytochemistry and ultrastructure. Virchows Arch 394: 255–267Google Scholar
  95. 95.
    Saint-Andre J-P, Rohmer V, Alhenc-Gelas F, Menard J, Bigorgne J-C, Corvol P (1986) Presence of renin, angiotensinogen and converting enzyme in human lactotroph cells and prolactin adenomas. J Clin Endocr Metab 63: 231–237PubMedCrossRefGoogle Scholar
  96. 96.
    Scheithauer BW, Kovacs K, Randall RV (1983) The pituitary in untreated Addison’s disease: a histologic and immunocytologic study of 18 adenohypo-physes. Arch Pathol La Med 107: 484–487Google Scholar
  97. 97.
    Scheithauer BW (1984a) Surgical pathology of the pituitary: the adenomas. Part 1. Pathol Annu 19: 317–374PubMedGoogle Scholar
  98. 98.
    Scheithauer BW (1984b) Surgical pathology of the pituitary: the adenomas. Part 2. Pathol Annu 19: 269–329PubMedGoogle Scholar
  99. 99.
    Scheithauer BW, Kovacs K, Randall RV, Ryan N (1985) Pituitary gland in hypothyroidism. Histologic and immunocytologic study. Arch Pathol Lab Med 109: 499–504PubMedGoogle Scholar
  100. 100.
    Scheithauer BW, Kovacs K, Laws ER Jr, Randall RV (1986a) Pathology of invasive pituitary adenomas with special reference to functional classification. J Neurosurg 65: 733–744PubMedCrossRefGoogle Scholar
  101. 101.
    Scheithauer BW, Horvath E, Kovacs K, Laws ER, Randall RV, Ryan N (1986b) Plurihormonal pituitary adenomas. Semin Diagn Pathol 6: 69–82Google Scholar
  102. 102.
    Scheithauer B W, Kovacs K, Randall RV, Ryan N (1989) Effects of estrogen on the human pituitary: a clinicopathologic study. Mayo Clin Proc 64: 1077–1084PubMedGoogle Scholar
  103. 103.
    Schonbrunn A, Krasnoff M, Westendorg JM, Tashjian AH (1980) Epidermal growth factor and thyrotropin-releasing hormone act similarly on a clonal pituitary cell strain. Modulation of hormone production and inhibition of cell proliferation. J Cell Biol 85: 786–797PubMedCrossRefGoogle Scholar
  104. 104.
    Schulte HM, Oldfield EH, Allolio B, Katz DA, Berkman RA, Ali IU (1991) Clonal composition of pituitary adenomas in patients with Cushing’s disease: determination by X-chromosome inactivation analysis. J Clin Endocrinol Metab 73: 1302–1308PubMedCrossRefGoogle Scholar
  105. 105.
    Schweigerer L, Neufeld G, Gospodarowicz D (1987) Basic fibroblastic growth factor as a growth inhibitor for cultured human tumor cells. J Clin Invest 80: 1516–1520PubMedCrossRefGoogle Scholar
  106. 106.
    Selman WR, Laws ER, Scheithauer BW, Carpenter SM (1986) The occurrence of dual invasion in pituitary adenomas. J Neurosurg 64: 402–407PubMedCrossRefGoogle Scholar
  107. 107.
    Smallridge RC (1987) Thyrotropin-secreting pituitary tumors. Endocrinol Metab Clin North Am 16: 765–792PubMedGoogle Scholar
  108. 108.
    Spada A, Arosio M, Bochicchio D, Bassoni N, Vallar L, Bassetti M, Faglia G (1990) Clinical, biochemical and morphological correlates in patients bearing growth hormone secreting with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71: 1421–1426PubMedCrossRefGoogle Scholar
  109. 109.
    Stefaneanu L, Horvath E, Kovacs K (1989) Argyrophilic organizer region proteins (AgNORs) in adenohypophysial cells and adenomas of the human pituitary. Mod Pathol 2: 192–199PubMedGoogle Scholar
  110. 110.
    Stefaneanu L, Kovacs K, Horvath E, Lloyd RV, Buchfelder M, Fahlbusch R, Smythe H (1994) In situ hybridization of estrogen receptor mRNA in human adenohypophysial cells and pituitary adenomas. J Clin Endocrincol Metab 78: 83–88CrossRefGoogle Scholar
  111. 111.
    Sumi T, Stefaneanu L, Kovacs K, Asa SL, Rindi G (1993) Immunohistochemical study of p53 protein in human and animal pituitary tumors. Endocr Pathol 4: 95–99CrossRefGoogle Scholar
  112. 112.
    Thapar K, Horvath E, Kovacs K, Muller PJ (1992) Pituitary adenomas: recent advances in classification, histopathology and molecular biology. Diagn Oncol 2: 145–167Google Scholar
  113. 113.
    Thapar K, Kovacs K, Laws E, Muller PJ (1993a) Pituitary adenomas: current concepts in classification, histopathology, and molecular biology. Endocrinologist 3: 39–57CrossRefGoogle Scholar
  114. 114.
    Thapar K, Stefaneanu L, Kovacs K, Horvath E, Asa SL (1993b) Plurihormonal pituitary tumors: beyond the one cell-one hormone theory. Endocr Pathol 4: 1–3CrossRefGoogle Scholar
  115. 115.
    Thapar K, Kovacs K, Stefaneanu L, Smythe H, Laws ER Jr (1993c) Insulinlike growth factor 1 gene expression in human pituitary adenomas: an in situ hybridization study. Scientific Program 61st Annual Meeting, American Association of Neurological Surgeons, April 1993, Boston, pp 359Google Scholar
  116. 116.
    Theill LE, Castrillo J-L, Wu D, Karin M (1989) Dissection of the functional domains of the pituitary specific transcription factor GHF-1. Nature 342: 945–948PubMedCrossRefGoogle Scholar
  117. 117.
    Thorner MO, Vance ML, Horvath E, Kovacs K (1992) The anterior pituitary. In: Wilson JD, Foster DW (eds) Williams textbook of endocrinology, 8th ed. Saunders, Philadelphia, pp 221–310Google Scholar
  118. 118.
    Tordjman K, Stern N, Ouaknine G, Yossiphov Y, Razon N, Nordenskjold M, Friedman E (1993) Activating mutations of the Gs alpha gene in nonfunctioning pituitary tumors. J Clin Endocrinol Metab 77: 765–769PubMedCrossRefGoogle Scholar
  119. 119.
    U SH, Kelly P, Lee WH (1988) Abnormalities of human growth hormone gene and protooncogenes in some human pituitary adenomas. Mol Endocrinol 2: 85–89CrossRefGoogle Scholar
  120. 120.
    Vallar L, Spada A, Giannattasio G (1987) Altered Gs and adenylate cyclase activity in human GH secreting pituitary tumors. Nature 330: 566–567PubMedCrossRefGoogle Scholar
  121. 121.
    Vance ML (1990) Growth hormone releasing hormone. Clin Chem 36: 415–420PubMedGoogle Scholar
  122. 122.
    Vrontakis ME, Sano T, Kovacs K, Friesen HG (1990) Presence of glananin-like immunoreactivity in nontumorous corticotrophs and corticotroph adenomas of the human pituitary. J Clin Endocrinol Metab 70: 747–751PubMedCrossRefGoogle Scholar
  123. 123.
    Weinberg RA (1991) Tumor suppressor genes. Science 254: 1138–1146PubMedCrossRefGoogle Scholar
  124. 124.
    Weinstein LS, Shenkar A, Gejman P, Martino MJ, Friedman E, Spiegel AM (1991) Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 325: 1688–1695PubMedCrossRefGoogle Scholar
  125. 125.
    Wilson CB, Tyrell JB, Fitzgerald PA, Pitts L (1979) Neurosurgical aspects of Cushing’s disease and Nelson’s syndrome. In: Tindall GT, Collins WF (eds) Clinical management of pituitary disorders. Raven, New York, pp 99229–99238Google Scholar
  126. 126.
    Woodruff MFA, Ansell JD, Forbes GM, Gordon JC, Burton DI, Micklem HS (1982) Clonal interaction in tumours. Nature 299: 822–824PubMedCrossRefGoogle Scholar
  127. 127.
    Yamashita S, Weiss M, Melmed S (1986) Insulin-like growth factor 1 regulates growth hormone secretion and messenger ribonucleic acid levels in human pituitary tumors. J Clin Endocrinol Metab 63: 730–734PubMedCrossRefGoogle Scholar
  128. 128.
    Ying S-L (1988) Inhibins, activins, and follistatins. Gonadal proteins modulating the secretion of follicle-stimulating homone. Endocrin Rev 9: 267–293CrossRefGoogle Scholar
  129. 129.
    Yoshimoto K, Iwahana H, Fukuda A, Sano T, Itakura M (1993) Rare mutations of the Gs alpha subunit in human endocrine tumors. Mutation detection by polymerase chain reaction-primer introduced restriction analysis. Cancer 72: 1286–1393CrossRefGoogle Scholar
  130. 130.
    Zuber M, Tan EM, Ryoji M (1989) Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells. Mol Cell Biol 9: 57–66PubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1995

Authors and Affiliations

  • K. Thapar
    • 1
  • K. Kovacs
    • 2
  • E. R. Laws
    • 3
  1. 1.Department of NeurosurgerySt. Michael’s Hospital, University of TorontoTorontoCanada
  2. 2.Department of PathologySt. Michael’s Hospital, University of TorontoTorontoCanada
  3. 3.Department of Neurological SurgeryUniversity of VirginiaCharlottesvilleUSA

Personalised recommendations