Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 5 , Pages 625-638 , October 2009

Non-functioning pituitary adenomas

  • Yona Greenman, MD (Assistant Professor in Endocrinology)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +972 36973899; Fax: +972 36973053.
    • ,
  • Naftali Stern, MD (Professor in Endocrinology)

      Affiliations

    • Tel: +972 36973732; Fax: +972 36974578.

References 

  1. Kwekkeboom DJ, de Jong FH, Lamberts SW. Gonadotropin 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
  2. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas. A systematic review. Cancer. 2004;101:613–619
  3. Buurman H, Saeger W. Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. European Journal of Endocrinology. 2006;154:753–756
  4. Davis JRE, Farrel WE, Clayton RN. Pituitary tumors. Reproduction. 2001;121:363–371
  5. Daly AF, Rixhon M, Adam C, et al. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liège, Belgium. Journal of Clinical Endocrinology and Metabolism. 2006;91:4769–4775
  6. Saeger W, Lüdecke DK, Buchfelder M, et al. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. European Journal of Endocrinology. 2007;156:203–216
  7. Yamada S, Ohyama K, Taguchi M, et al. A study of the correlation between morphological findings and biological activities in clinically nonfunctioning pituitary adenomas. Neurosurgery. 2007;61:580–585
  8. Al-Shraim M, Asa SL. The 2004 World Health Organization classification of pituitary tumors: what is new?. Acta Neuropathologica. 2006;111:1–7
  9. 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. The Journal of Clinical Endocrinology and Metabolism. 1992;74:1128–1134
  10. Ingraham HA, Chen R, Mangalam HJ, et al. A tissue specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell. 1988;55:519–529
  11. Lamolet B, Pulichino AM, Lamonerie T, et al. A pituitary cell restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell. 2001;104:849–859
  12. Asa SL. Practical pituitary pathology. What does the pathologist need to know?. Archives of Pathology and Laboratory Medicine. 2008;132:1231–1240
  13. Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumors but do not recur more frequently. Clinical Endocrinology. 2003;58:59–64
  14. Horvath E, Kovacs K, Smyth HS, et al. A novel type of pituitary adenoma: morphological features and clinical correlations. The Journal of Clinical Endocrinology and Metabolism. 1988;66:1111–1118
  15. Nomikos P, Ladar C, Fahlbusch R, et al. Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas – a study on 721 patients. Acta Neurochirurgica. 2004;146:27–35
  16. Losa M, Mortini P, Barzaghi R, et al. Early results of surgery in patients with nonfunctioning pituitary adenomas and analysis of the risk of tumor recurrence. Journal of Neurosurgery. 2008;108:525–532
  17. Chang EF, Zada G, Kim S, et al. Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. Journal of Neurosurgery. 2008;108:736–745
  18. Arafah BM, Prunty D, Ybarra J, et al. The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. 2000;85:1789–1793
  19. Greenman Y, Ouaknine G, Veshchev I, et al. Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth. Clinical Endocrinology. 2003;58:763–769
  20. Kim SH, Lee KC, Kim SH. Cranial nerve palsies accompanying pituitary tumor. Journal of Clinical Neuroscience. 2007;14:1158–1162
  21. Deepak D, Daousi C, Javadpour M, et al. Macroprolactinomas and epilepsy. Clinical Endocrinology. 2007;66:503–507
  22. Carroll WR, Cohen S, Sullivan MJ. Spontaneous CSF rhinorrhea: an unusual presentation of a pituitary adenoma. Otolaryngology-Head and Neck Surgery. 1991;104:380–383
  23. Dekkers OM, Pereira AM, Roelfsema JHC, et al. Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. The Journal of Clinical Endocrinology and Metabolism. 2006;91:1796–1801
  24. Arafah BM. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. 1986;62:1173–1179
  25. Greenman Y, Tordjman K, Kisch E, et al. Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas. The Journal of Clinical Endocrinology and Metabolism. 1995;80:1577–1583
  26. Webb SM, Rigla M, Wägner A, et al. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. 1999;84:3696–3700
  27. Young WF, Scheithauer BW, Kovacs KT, et al. Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clinic Proceedings. 1996;71:649–656
  28. Hanson PL, Aylwin SJB, Monson JP, et al. FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas. European Journal of Endocrinology. 2005;152:363–370
  29. Cooper O, Geller JL, Melmed S. Ovarian hyperstimulation syndrome caused by an FSH-secreting pituitary adenoma. Nature Clinical Practice. Endocrinology and Metabolism. 2008;4:234–238
  30. Snyder PJ, Sterling FH. Hypersecretion of LH and FSH by a pituitary adenoma. The Journal of Clinical Endocrinology and Metabolism. 1976;42:544–550
  31. Heseltine D, White MC, Kendall-Taylor P, et al. Testicular enlargement and elevated serum inhibin concentrations occur in patients with pituitary macroadenomas secreting follicle stimulating hormone. Clinical Endocrinology. 1989;31:411–423
  32. Faggiano M, Criscuolo T, Perrone I, et al. Sexual precocity in a boy due to hypersecretion of LH and prolactin by a pituitary adenoma. Acta Endocrinologica. 1983;102:167–172
  33. Abrosi B, Bassetti M, Ferrario R, et al. Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumour: biosynthetic characterization and clinical studies. Acta Endocrinologica. 1990;122:569–576
  34. Daneshdoost L, Genarelli TA, Bashey HM, et al. Recognition of gonadotroph adenomas in women. The New England Journal of Medicine. 1991;324:589–594
  35. Somjen D, Tordjman K, Kohen F, et al. Combined βFSH and βLH response to TRH in patients with clinically non-functioning pituitary adenomas. Clinical Endocrinology. 1997;46:555–562
  36. Nobels FRE, Kwekkeboom DJ, Coopman W, et al. A comparison between the diagnostic value of gonadotropins, α-subunits, and chromogranin-A and their response to thyrotropin-releasing hormone in clinically nonfunctioning, α-subunit-secreting, and gonadotroph pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. 1993;77:784–789
  37. Yoshino A, Katayama Y, Watanabe T, et al. Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests. Acta Neurochirurgica. 2007;149:557–565
  38. Karavitaki N, Thanabalasingham G, Shore HCA, et al. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clinical Endocrinology. 2006;65:524–529
  39. Naidich MJ, Russel EJ. Current approaches to imaging of the sellar region and pituitary. Endocrinology and Metabolism Clinics of North America. 1999;28:45–79
  40. Rao VJ, James RA, Mitra D. Imaging characteristics of common suprasellar lesions with emphasis on MRI findings. Clinical Radiology. 2008;63:939–947
  41. Reincke M, Allolio B, Saeger J, et al. The “incidentaloma” of the pituitary gland. Is neurosurgery required?. JAMA. 1990;263:2772–2776
  42. Donovan LE, Corenblum B. The natural history of pituitary incidentaloma. Archives of Internal Medicine. 1995;155:181–183
  43. Sanno N, Oyama K, Tahara S, et al. A survey of pituitary incidentaloma in Japan. European Journal of Endocrinology. 2003;149:123–127
  44. Nishizawa S, Ohta S, Yokoyama T, et al. Therapeutic strategies for incidentally found pituitary tumors (“Pituitary Incidentalomas”). Neurosurgery. 1998;43:1344–1348
  45. Igarashi T, Saeki N, Yamaura A. Long-term magnetic resonance imaging follow-up of asymptomatic sellar tumors – their natural history and surgical indications. Neurologia Medico-Chirurgica (Tokyo). 1999;39:592–599
  46. Dekkers OM, Hammer S, de Keizer RJW, et al. The natural course of non-functioning pituitary macroadenomas. European Journal of Endocrinology. 2007;156:217–224
  47. Arita K, Tominaga A, Sugiyama K, et al. Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. Journal of Neurosurgery. 2006;104:884–891
  48. Feldkamp J, Santen R, Harms E, et al. Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone-secreting adenomas-results of a prospective study. Clinical Endocrinology. 1999;51:109–113
  49. Karavitaki N, Collison K, Halliday J, et al. What is the natural history of nonoperated nonfunctioning pituitary adenomas?. Clinical Endocrinology. 2007;67:938–943
  50. Black PM, Zervas NT, Candia G. Management of large pituitary adenomas by transsphenoidal surgery. Surgical Neurology. 1988;29:443–447
  51. Ferrante E, Ferraroni M, Castrignano T, et al. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. European Journal of Endocrinology. 2006;155:823–829
  52. Zhang X, Fein Z, Zhang J, et al. Management of nonfunctioning pituitary adenomas with suprasellar extensions by transsphenoidal microsurgery. Surgical Neurology. 1999;52:380–385
  53. Park P, Chandler W, Barkan A, et al. The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery. 2004;55:100–106
  54. Honneger J, Ernemann U, Psaras T, et al. Objective criteria for successful transsphenoidal removal of suprasellar nonfunctioning pituitary adenomas. A prospective study. Acta Neurochirurgica (Wien). 2007;149:21–29
  55. Ciric I, Ragin A, Baumgartner C, et al. Complications of transsphenoidal surgery: results of a national survey, review of the literature and personal experience. Neurosurgery. 1997;40:225–236
  56. Barker FG, Klibanski A, Swearingen B. Transsphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4709–4719
  57. Nemergut EC, Zuo Z, Jane JA, et al. Predictors of diabetes insipidus after transsphenoidal surgery: a review of 881 patients. Journal of Neurosurgery. 2005;103:448–454
  58. Comtois R, Beauregard H, Somma M, et al. The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer. 1991;68:860–866
  59. Kremmer P, Forsting M, Ranaei G, et al. Magnetic resonance imaging after transsphenoidal surgery of clinically nonfunctional pituitary macroadenomas and its impact on detecting residual adenoma. Acta Neurochirurgica(Wien). 2002;144:433–443
  60. Turner HE, Stratton IM, Byrne JV, et al. Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation – a follow-up study. Clinical Endocrinology. 1999;51:281–284
  61. Kontogeorgos G. Predictive markers of pituitary adenoma behavior. Neuroendocrinology. 2006;83:179–188
  62. Thapar K, Kovacs K, Scheithauer B, et al. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery. 1996;38:99–107
  63. Mastronardi L, Guiducci A, Spera C, et al. Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody. Journal of Clinical Pathology. 1999;52:107–111
  64. Honegger J, Prettin C, Feuerhake F, et al. Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness. Journal of Neurosurgery. 2003;99:674–679
  65. Gejman R, Swearingen B, Hedley-Whyte ET. Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Human Pathology. 2008;38:758–766
  66. Losa M, Franzin A, Mangili F, et al. Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long term follow-up studies. Neurosurgery. 2000;47:1313–1319
  67. Dubois S, Guyetant S, Menei P, et al. Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery. European Journal of Endocrinology. 2007;157:141–147
  68. Gittoes NJL, Bates AS, Tse W, et al. Radiotherapy for non-functioning pituitary tumours. Clinical Endocrinology. 1998;48:331–337
  69. Erfurth EM, Bulow B, Svahn-Tapper G, et al. Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. The Journal of Clinical Endocrinology and Metabolism. 2002;87:4892–4899
  70. Minniti G, Traish D, Ashley S, et al. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenomas; update after an additional 10 years. The Journal of Clinical Endocrinology and Metabolism. 2005;90:800–804
  71. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism, West Midlands prospective hypopituitary study group. Lancet. 2001;357:425–431
  72. Tsang RW, Brierley JD, Panzarella T, et al. Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. International Journal of Radiation Oncology Biology Physics. 1994;30:557–565
  73. Sheehan JP, Kondziolka D, Flickinger J, et al. Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. Journal of Neurosurgery. 2002;97(Suppl. 5):408–414
  74. Kanner AA, Corn BW, Greenman Y. Radiotherapy of nonfunctioning and gonadotroph adenomas. Pituitary. 2009;12:15–22
  75. Minniti G, Jafrain-Rea ML, Osti M, et al. Radiotherapy for nonfunctioning pituitary adenomas: from conventional to modern stereotactic radiation techniques. Neurosurgical Review. 2007;30:167–176
  76. Bevan JS, Burke CW. Non-functioning pituitary adenomas do not regress during bromocriptine therapy but possess membrane-bound dopamine receptors which bind bromocriptine. Clinical Endocrinology. 1986;25:561–572
  77. Renner U, Arzberger T, Pagotto U, et al. Heterogeneous dopamine D2 receptor subtype messenger ribonucleic acid expression in clinically nonfunctioning pituitary adenomas. The Journal of Clinical Endocrinology and Metabolism. 1998;83:1368–1375
  78. Pivonello R, Matrone C, Filippela M, et al. Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. The Journal of Clinical Endocrinology and Metabolism. 2004;89:1674–1683
  79. Kwekkeboom DJ, Hofland LJ, van Koetsveld PM, et al. Bromocriptine increasingly suppresses the in vitro gonadotropin and alpha-subunit release from pituitary adenomas during long term culture. The Journal of Clinical Endocrinology and Metabolism. 1990;71:718–724
  80. Kwekkeboom DJ, Lamberts SW. Lon-term treatment with the dopamine agonist CV 205-502 of patients with a clinically non-functioning, gonadotroph, or alpha-subunit secreting pituitary adenoma. Clinical Endocrinology. 1992;36:171–176
  81. Florio T, Barbieri F, Spaziante R, et al. Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study. Endocrine-related Cancer. 2008;15:583–596
  82. Colao A, Di Somma C, Pivonello R, et al. Medical therapy for clinically non-functioning pituitary adenomas. Endocrine-related Cancer. 2008;15:905–915
  83. Greenman Y, Tordjman K, Osher E, et al. Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth. Clinical Endocrinology. 2005;63:39–394
  84. Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. The New England Journal of Medicine. 2007;356:39–46
  85. Lancellotti P, Livadariu E, Markov M, et al. Cabergoline and the risk of valvular lesions in endocrine disease. European Journal of Endocrinology. 2008;159:1–5
  86. Greenman Y, Melmed S. Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. The Journal of Clinical Endocrinology and Metabolism. 1994;79:724–729
  87. Taboada GF, Luque RM, Bastos W, et al. Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. European Journal of Endocrinology. 2007;156:65–74
  88. Pawlikowski M, Lawnicka H, Pisarek H, et al. Effects of somatostatin-14 and the receptor specific somatostatin analogs on chromogranin A and alpha-subunit (alpha-SU) release from “clinically nonfunctioning ”pituitary adenoma cells incubated in vitro. Journal of Physiology and Pharmacology. 2007;58:179–188
  89. Florio T, Thellung S, Arena S, et al. Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro. European Journal of Endocrinology. 1999;141:396–408
  90. Zatelli MC, Piccin D, Bottoni A, et al. Evidence for differential effects of selective somatostatin receptor subtype agonists on α-subunit and chromogranin-A secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro. The Journal of Clinical Endocrinology and Metabolism. 2004;89:5181–5188
  91. Zatelli MC, Piccin D, Vignalli C, et al. Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocrine-related Cancer. 2007;14:91–102
  92. Rocheville M, Lange DC, Kumar U, et al. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science. 2000;288:154–157
  93. Andersen M, Bjerre P, Henrik D, et al. In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas. Clinical Endocrinology. 2001;54:23–30
  94. Dekkers OM, van der Klaauw AA, Pereira AM, et al. Quality of life is decreased after treatment for nonfunctioning pituitary macroadenoma. The Journal of Clinical Endocrinology and Metabolism. 2006;91:3364–3369
  95. van der Klaauw AA, Kars M, Biermasz NR, et al. Disease-specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas. Clinical Endocrinology. 2008;69:775–784
  96. Page RC, Hammersley MS, Burke CW, et al. An account of the quality of life of patients after treatment for non-functioning pituitary tumours. Clinical Endocrinology. 1997;46:401–406
  97. van Beek AP, van den Bergh ACM, van den berg LM, et al. Radiotherapy is not associated with reduced quality of life and cognitive function in patients treated for nonfunctioning pituitary adenoma. International Journal of Radiation Oncology Biology Physics. 2007;68:986–991
  98. Lindholm J, Nielsen H, Bjerre P, et al. Hypopituitarism and mortality in pituitary adenomas. Clinical Endocrinology. 2006;65:51–58
  99. Fainstein Day P, Guitelman M, Artese R, et al. Retrospective multicentric study of pituitary incidentalomas. Pituitary. 2004;7:145–148
  100. Lillehei KO, Kirschman DL, Kleinschmidt-DeMasters BK, et al. Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas. Neurosurgery. 1998;43:432–438
  101. Woolons AC, Hunn MK, Rajapakse YR, et al. Nonfunctioning pituitary adenomas: indications for postoperative radiotherapy. Clinical Endocrinology. 2000;53:713–717
  102. Soto-Ares G, Cortet-Rudelli C, Assaker R, et al. MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. European Journal of Endocrinology. 2002;146:179–186
  103. van den Bergh ACM, van den Bergh G, Schoorl MA, et al. Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: beneficial effect on local control without additional negative impact on pituitary function and life expectancy. International Journal of Radiation Oncology Biology Physics. 2007;67:863–869
  104. O'Sullivan EP, Woods C, Glynn N, et-al. The natural history of surgically treated but radiotherapy naïve non-functioning pituitary adenomas. Clinical Endocrinology. doi:10.1111/j1365–2265.2009.03583.x.

PII: S1521-690X(09)00051-7

doi: 10.1016/j.beem.2009.05.005

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 5 , Pages 625-638 , October 2009

Article Tools

* Image Usage & Resolution