DOI QR코드

DOI QR Code

Radiological Apoplexy and Its Correlation with Acute Clinical Presentation, Angiogenesis and Tumor Microvascular Density in Pituitary Adenomas

  • Lee, Jung-Sup (Department of Neurosurgery, College of Medicine, Chung-Ang University) ;
  • Park, Yong-Sook (Department of Neurosurgery, College of Medicine, Chung-Ang University) ;
  • Kwon, Jeong-Taik (Department of Neurosurgery, College of Medicine, Chung-Ang University) ;
  • Nam, Taek-Kyun (Department of Neurosurgery, College of Medicine, Chung-Ang University) ;
  • Lee, Tae-Jin (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Kim, Jae-Kyun (Department of Neurosurgery, College of Medicine, Chung-Ang University)
  • Received : 2011.04.19
  • Accepted : 2011.10.17
  • Published : 2011.10.28

Abstract

Objective : Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy. Methods : Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31. Results : Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy. Conclusion : While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.

Keywords

References

  1. Arita K, Kurisu K, Tominaga A, Sugiyama K, Eguchi K, Hama S, et al. : Relationship between intratumoral hemorrhage and overexpression of vascular endothelial growth factor (VEGF) in pituitary adenoma. Hiroshima J Med Sci 53 : 23-27, 2004
  2. Banerjee SK, Zoubine MN, Tran TM, Weston AP, Campbell DR : Overexpression of vascular endothelial growth factor164 and its co-receptor neuropilin-1 in estrogen-induced rat pituitary tumors and GH3 rat pituitary tumor cells. Int J Oncol 16 : 253-260, 2000
  3. Bergers G, Benjamin LE : Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3 : 401-410, 2003 https://doi.org/10.1038/nrc1093
  4. Biousse V, Newman NJ, Oyesiku NM : Precipitating factors in pituitary apoplexy. J Neurol Neurosurg Psychiatry 71 : 542-545, 2001 https://doi.org/10.1136/jnnp.71.4.542
  5. Bonneville JF, Cattin F, Gorczyca W, Hardy J : Pituitary microadenomas: early enhancement with dynamic CT--implications of arterial blood supply and potential importance. Radiology 187 : 857-861, 1993 https://doi.org/10.1148/radiology.187.3.8497646
  6. Ferrara N : Vascular endothelial growth factor: Basic science and clinical progress. Endocr Rev 25 : 581-611, 2004 https://doi.org/10.1210/er.2003-0027
  7. Findling JW, Tyrrell JB, Aron DC, Fitzgerald PA, Wilson CB, Forsham PH : Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropin-producing pituitary adenoma. J Clin Endocrinol Metab 52 : 95-97, 1981 https://doi.org/10.1210/jcem-52-1-95
  8. Garcia de la Torre N, Wass JA, Turner HE : Antiangiogenic effects of somatostatin analogues. Clin Endocrinol (Oxf) 57 : 425-441, 2002 https://doi.org/10.1046/j.1365-2265.2002.01619.x
  9. Gorczyca W, Hardy J : Microadenomas of the human pituitary and their vascularization. Neurosurgery 22 : 1-6, 1988 https://doi.org/10.1227/00006123-198801000-00001
  10. Gould VE, Wagner BM : Angiogenesis: an expanding universe. Hum Pathol 33 : 1061-1063, 2002 https://doi.org/10.1053/hupa.2002.130311
  11. Hicklin DJ, Ellis LM : Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23 : 1011-1027, 2005 https://doi.org/10.1200/JCO.2005.06.081
  12. Horak ER, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, et al. : Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340 : 1120-1124, 1992 https://doi.org/10.1016/0140-6736(92)93150-L
  13. Liotta LA, Steeg PS, Stetler-Stevenson WG : Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64 : 327-336, 1991 https://doi.org/10.1016/0092-8674(91)90642-C
  14. Liu ZH, Chang CN, Pai PC, Wei KC, Jung SM, Chen NY, et al. : Clinical features and surgical outcome of clinical and subclinical pituitary apoplexy. J Clin Neurosci 17 : 694-699, 2010 https://doi.org/10.1016/j.jocn.2009.11.012
  15. Lloyd RV, Scheithauer BW, Kuroki T, Vidal S, Kovacs K, Stefaneanu L : Vascular endothelial growth factor (VEGF) expression in human pituitary adenomas and carcinomas. Endocr Pathol 10 : 229-235, 1999 https://doi.org/10.1007/BF02738884
  16. Lohrer P, Gloddek J, Hopfner U, Losa M, Uhl E, Pagotto U, et al. : Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro. Neuroendocrinology 74 : 95-105, 2001 https://doi.org/10.1159/000054675
  17. Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA : Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 340 : 145-146, 1992 https://doi.org/10.1016/0140-6736(92)93217-B
  18. McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, et al. : Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors. J Clin Endocrinol Metab 87 : 4238-4244, 2002 https://doi.org/10.1210/jc.2002-020309
  19. Mohr G, Hardy J : Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol 18 : 181-189, 1982 https://doi.org/10.1016/0090-3019(82)90388-3
  20. Murad-Kejbou S, Eggenberger E : Pituitary apoplexy: evaluation, management, and prognosis. Curr Opin Ophthalmol 20 : 456-461, 2009 https://doi.org/10.1097/ICU.0b013e3283319061
  21. Nawar RN, AbdelMannan D, Selman WR, Arafah BM : Pituitary tumor apoplexy: a review. J Intensive Care Med 23 : 75-90, 2008 https://doi.org/10.1177/0885066607312992
  22. Oh H, Takagi H, Otani A, Koyama S, Kemmochi S, Uemura A, et al. : Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF) : A mechanism contributing to VEGF-induced angiogenesis. Proc Natl Acad Sci U S A 99 : 383-388, 2002 https://doi.org/10.1073/pnas.012074399
  23. Ostrov SG, Quencer RM, Hoffman JC, Davis PC, Hasso AN, David NJ : Hemorrhage within pituitary adenomas: how often associated with pituitary apoplexy syndrome? AJR Am J Roentgenol 153 : 153-160, 1989 https://doi.org/10.2214/ajr.153.1.153
  24. Pizarro CB, Oliveira MC, Pereira-Lima JF, Leães CG, Kramer CK, Schuch T, et al. : Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker. Neuropathology 29 : 40-44, 2009 https://doi.org/10.1111/j.1440-1789.2008.00937.x
  25. Semple PL, Jane JA, Lopes MB, Laws ER : Pituitary apoplexy : correlation between magnetic resonance imaging and histopathological results. J Neurosurg 108 : 909-915, 2008 https://doi.org/10.3171/JNS/2008/108/5/0909
  26. Tammela T, Enholm B, Alitalo K, Paavonen K : The biology of vascular endothelial growth factors. Cardiovasc Res 65 : 550-563, 2005 https://doi.org/10.1016/j.cardiores.2004.12.002
  27. Turgut M, Ozsunar Y, Basak S, Guney E, Kir E, Meteoglu I : Pituitary apoplexy : an overview of 186 cases published during the last century. Acta Neurochir (Wien) 152 : 749-761, 2010 https://doi.org/10.1007/s00701-009-0595-8
  28. Turner HE, Harris AL, Melmed S, Wass JA : Angiogenesis in endocrine tumors. Endocr Rev 24 : 600-632, 2003 https://doi.org/10.1210/er.2002-0008
  29. Turner HE, Nagy Z, Gatter KC, Esiri MM, Harris AL, Wass JA : Angiogenesis in pituitary adenomas and the normal pituitary gland. J Clin Endocrinol Metab 85 : 1159-1162, 2000 https://doi.org/10.1210/jc.85.3.1159
  30. Verrees M, Arafah BM, Selman WR : Pituitary tumor apoplexy: characteristics, treatment, and outcomes. Neurosurg Focus 16 : E6, 2004
  31. Wakai S, Fukushima T, Teramoto A, Sano K : Pituitary apoplexy : its incidence and clinical significance. J Neurosurg 55 : 187-193, 1981 https://doi.org/10.3171/jns.1981.55.2.0187
  32. Wakai S, Yamakawa K, Manaka S, Takakura K : Spontaneous intracranial hemorrhage caused by brain tumor : its incidence and clinical significance. Neurosurgery 10 : 437-444, 1982 https://doi.org/10.1227/00006123-198204000-00004
  33. Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J : Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143 : 401-409, 1993
  34. Yamada S, Takada K : Angiogenesis in pituitary adenomas. Microsc Res Tech 60 : 236-243, 2003 https://doi.org/10.1002/jemt.10262

Cited by

  1. The Prevalence and Natural History of Pituitary Hemorrhage in Prolactinoma vol.98, pp.6, 2013, https://doi.org/10.1210/jc.2013-1249
  2. Dissociated hypopituitarism after spontaneous pituitary apoplexy in acromegaly vol.17, pp.7, 2011, https://doi.org/10.4103/2230-8210.119518
  3. Pituitary apoplexy in a patient with suspected metastatic bronchogenic carcinoma vol.2014, pp.None, 2014, https://doi.org/10.1136/bcr-2013-202803
  4. Pituitary Apoplexy Secondary to Thrombocytopenia Due to Dengue Hemorrhagic Fever: A Case Report and Review of the Literature vol.20, pp.4, 2011, https://doi.org/10.4158/ep13319.cr
  5. Pituitary intratumoral hemorrhage during radiation therapy following partial removal of giant pituitary adenoma: A case report vol.3, pp.1, 2011, https://doi.org/10.4236/crcm.2014.31010
  6. Pituitary intratumoral hemorrhage during radiation therapy following partial removal of giant pituitary adenoma: A case report vol.3, pp.1, 2011, https://doi.org/10.4236/crcm.2014.31010
  7. Endocan, a new invasion and angiogenesis marker of pituitary adenomas vol.117, pp.3, 2011, https://doi.org/10.1007/s11060-014-1377-6
  8. Multicenter Study on Adult Growth Hormone Level in Postoperative Pituitary Tumor Patients vol.71, pp.2, 2015, https://doi.org/10.1007/s12013-014-0334-5
  9. Pituitary Apoplexy vol.36, pp.6, 2015, https://doi.org/10.1210/er.2015-1042
  10. Pseudotumor cerebri and pituitary apoplexy vol.115, pp.3, 2011, https://doi.org/10.1007/s13760-014-0393-9
  11. Pituitary Apoplexy After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitor: A Novel Complication vol.76, pp.2, 2011, https://doi.org/10.1055/s-0035-1554909
  12. MRI in the Evaluation of Acute Visual Syndromes vol.24, pp.6, 2015, https://doi.org/10.1097/rmr.0000000000000070
  13. Investigation of the growth patterns of non-functioning pituitary macroadenomas using volumetric assessments on serial MRI investigations vol.20, pp.1, 2011, https://doi.org/10.4102/sajr.v20i1.962
  14. Selective molecular biomarkers to predict biologic behavior in pituitary tumors vol.12, pp.3, 2011, https://doi.org/10.1080/17446651.2017.1312341
  15. Upregulation of microRNA-129-5p inhibits cell invasion, migration and tumor angiogenesis by inhibiting ZIC2 via downregulation of the Hedgehog signaling pathway in cervical cancer vol.19, pp.12, 2011, https://doi.org/10.1080/15384047.2018.1491497
  16. Landscape of Molecular Events in Pituitary Apoplexy vol.9, pp.None, 2011, https://doi.org/10.3389/fendo.2018.00107
  17. Imatinib Inhibits GH Secretion From Somatotropinomas vol.9, pp.None, 2011, https://doi.org/10.3389/fendo.2018.00453
  18. PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age vol.41, pp.None, 2011, https://doi.org/10.1016/j.anndiagpath.2019.04.016