Advertisement

Intraoperative optical identification of pituitary adenomas

  • M. Sam EljamelEmail author
  • Graham Leese
  • Harry Moseley
Clinical Study – patient studies

Abstract

Introduction The main goals of transsphenoidal pituitary surgery are total removal of pituitary adenomas (PAs) and preservation of normal pituitary functions. Achieving these goals is dependant upon the precise localisation of PAs during surgery, particularly secreting microadenomas. However, some microadenomas are invisible on preoperative imaging and during surgery, leading some surgeons to perform total hypophysectomy in many patients to achieve cure at the expense of panhypopituitrism. We have examined optical detection systems to identify PAs intraoperatively. This paper reports our preliminary findings. Methods A prospective observational study design. Technique Patients were given 20 mg/kg body weight 5-aminolevulinic acid (ALA) mixed in 30 ml of orange juice, orally 3 h before surgery. Surgery was performed in the supine position, under image guidance, through the right nostril using Storz 0 degree endoscope assisted with microsurgery as required. The endoscope was attached to photodiagnostic filters (PD) allowing switching the light from white to blue at the flick of a foot pedal. After the dura of the floor of the sella was incised a laser probe was inserted into the pituitary gland to identify the ALA-induced protoporphyrin IX spectroscopy at 632 nm, using an optical biopsy system (OBS). Once the adenoma was identified by the OBS it was exposed and examined by the PD system to detect fluorescence. The PA was removed and its type was confirmed by histopathology and correlated to the OBS and PD system findings. Patients Thirty consecutive patients were studied: 14 were non-functioning macroadenomas (NFA), 12 were secreting PAs and 4 pituitary cysts. The secreting PAs were GH (2), ACTH (3), prolactin (2) and gonadotrophins (5). Six were microadenomas (3 ACTH, 1 GH, 2 prolactin) and 20 were macroadenomas, of which 12 were invading macroadenomas. Twenty-four of these were examined by the OBS and the PD systems and six were examined by the PD system only. The true positive (sensitivity) of the PD and OBS systems were 80.8% (21/26) and 95.5% (21/22) respectively. The true negative (specificity) of PD and OBS were 75% (3/4) and 100% (2/2) respectively. The false negative rate of PD was 19.2% (5/26) and for OBS was 4.5% (1/22), while the false positive rate for PD was 25% (1/4) and for OBS was 0. Conclusion Intraoperative optical identification of pituitary adenomas is a feasible and reliable way to localize pituitary adenomas during transsphenoidal surgery and it may lead to improved cure rate and preservation of normal pituitary functions.

Keywords

Adenoma Acromegaly Cushing’s disease Localization Photodiagnosis Pituitary 

Notes

Acknowledgments

We would like to acknowledge the financial support of Barbara Stewart Cancer Trust and the staff in the Photobiology, Neurosurgical theatre, Ms Carol Goodman, Myles Padgett, Martin O’Dwyer and our patients who agreed to participate in this study.

References

  1. 1.
    Oruckaptan HH, Senmevsim O, Ozcan OE, Ozgen T (2000) Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol 53:211–219. doi: 10.1016/S0090-3019(00)00171-3 PubMedCrossRefGoogle Scholar
  2. 2.
    Yildiz F, Zorlu F, Erbas T, Atahan L (1999) Radiotherapy in the management of giant pituitary adenomas. Radiother Oncol 52:233–237. doi: 10.1016/S0167-8140(99)00098-5 PubMedCrossRefGoogle Scholar
  3. 3.
    Amar AP, Hinton DR, Krieger MD, Weiss MH (1999) Invasive pituitary adenomas: significance of proliferation parameters. Pituitary 2:117–122. doi: 10.1023/A:1009931413106 PubMedCrossRefGoogle Scholar
  4. 4.
    Anson JA, Segal MN, Baldwin NG, Neal D (1995) Resection of giant invasive pituitary tumors through a transfacial approach: technical case report. Neurosurgery 37:545–546. doi: 10.1097/00006123-199509000-00029 CrossRefGoogle Scholar
  5. 5.
    Ebersold MJ, Quast LM, Laws ER Jr, Scheithauer B, Randall RV (1984) Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 64:713–719Google Scholar
  6. 6.
    Majos C, Coll S, Aguilera C, Acebes JJ, Pons LC (1998) Imaging of giant pituitary adenomas. Neuroradiology 40:651–655. doi: 10.1007/s002340050657 PubMedCrossRefGoogle Scholar
  7. 7.
    Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr (2002) The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg 96:195–208PubMedGoogle Scholar
  8. 8.
    Scheithauer BW, Kovacs KT, Laws ER Jr, Randall RV (1986) Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65:733–744PubMedGoogle Scholar
  9. 9.
    Yokoyama S, Hirano H, Moroki K, Goto M, Imamura S, Kuratsu JI (2001) Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive? Neurosurgery 49:862–863. doi: 10.1097/00006123-200110000-00014 CrossRefGoogle Scholar
  10. 10.
    Jenkins D, O’Brien I, Johnson A, Shakespear R, Sheppard MC, Stewart PM (1995) The Birmingham pituitary database: auditing the outcome of treatment of acromegaly. Clin Endocrinol (Oxf) 43:517–522. doi: 10.1111/j.1365-2265.1995.tb02913.x OxfCrossRefGoogle Scholar
  11. 11.
    Kreutzer J, Vance ML, Lopes MB, Laws ER Jr (2001) Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 86:4072–4077. doi: 10.1210/jc.86.9.4072 PubMedCrossRefGoogle Scholar
  12. 12.
    Manipalam TJ, Tyrell JB, Wilson CB (1988) Transsphenoidal microsurgery for Cushing’s disease: a report of 216 cases. Ann Intern Med 109:487–493Google Scholar
  13. 13.
    Buchfelder M, Fahlbusch R, Schott W, Honegger J (1991) Long-term follow-up results in hormonally active pituitary adenomas after primary successful transsphenoidal surgery. Acta Neurochir Suppl (Wien) 53:72–76Google Scholar
  14. 14.
    Bonelli FS, Huston J, Carpenter PC, Erickson D, Young WF Jr, Meyer FB (2000) Adrenocorticotropic hormone-dependent Cushing’s syndrome: sensitivity and specificity of inferior petrosal sinus sampling. AJNR Am J Neuroradiol 21:690–696PubMedGoogle Scholar
  15. 15.
    Batista D, Courkoutsakis NA, Oldfield EH, Griffin KJ, M Kei, Patronas NJ, Stratakis SA (2005) Detection of ACTH-secreting pituitary adenomas by magnetic resonance imaging (MRI) in children and adolescents with Cushing disease. J Clin Endocrinol Metab 90:5134–5140PubMedCrossRefGoogle Scholar
  16. 16.
    Indrajit IK, Chidambaranathan Sundar NK, Ahmed I (2001) Value of dynamic MRI imaging in pituitary adenomas. Neuroradiology 11:185–190. doi: 10.1007/s00062-001-2323-5 CrossRefGoogle Scholar
  17. 17.
    Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler GB, Loriaux DL (1991) Petrosal sinus sampling with and without corticotrophin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med 325:897–905PubMedGoogle Scholar
  18. 18.
    Schulte HM, Allolio B, Günther RW, Benker G, Winkelmann W, Ohnhaus EE, Reinwein D (1988) Selective bilateral and simultaneous catheterization of the inferior petrosal sinus: CRF stimulates prolactin secretion from ACTH-producing microadenomas in Cushing’s disease. Clin Endocrinol (Oxf) 28:289–295. doi: 10.1111/j.1365-2265.1988.tb01215.x CrossRefGoogle Scholar
  19. 19.
    Kaltsas GA, Giannulis MG, Newell-Price JD, Trainer PJ, Besser GM, Grossman AB (1999) A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 84:487–492. doi: 10.1210/jc.84.2.487 PubMedCrossRefGoogle Scholar
  20. 20.
    Booth GL, Redelmeier DA, Grosma H, Kovac K, Smyth HS, Ezzat S (1998) Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for localizing pituitary pathology in patients with Cushing’s disease. J Clin Endocrinol Metab 83:2291–2295. doi: 10.1210/jc.83.7.2291 PubMedCrossRefGoogle Scholar
  21. 21.
    López J, Barceló B, Lucas T, Salame F, Alameda C, Boronat M, Salto L, Estrada J (1996) Petrosal sinus sampling for diagnosis of Cushing’s disease: evidence of false negative results. Clin Endocrinol (Oxf) 45:147–257. doi: 10.1046/j.1365-2265.1996.d01-1550.x CrossRefGoogle Scholar
  22. 22.
    Watson JC, Shawker H, Nieman LK, De Vroom HL, Doppman JL, Oildfield EH (1998) Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing’s disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg 89:927–932PubMedCrossRefGoogle Scholar
  23. 23.
    Miller DL, Doppman JL, Peterman SB, Nieman LK, Oldfield EH, Chang R (1992) Neurologic complications of petrosal sinus sampling. Radiology 185:143–147PubMedGoogle Scholar
  24. 24.
    Lefournier V, Gatta B, Martinie M, Vasdev A, Tabarin A, Bessou P, Berge J, Bachelot I, Chabre O (1999) One transient neurological complication (sixth nerve palsy) in 166 consecutive inferior petrosal sinus samplings for the etiological diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 84:3401–3402. doi: 10.1210/jc.84.9.3401 PubMedCrossRefGoogle Scholar
  25. 25.
    Obuobie K, Davies JS, Ogunko A, Scanlon MF (2000) Venous thrombo-embolism following inferior petrosal sinus sampling in Cushing’s disease. J Endocrinol Invest 23:542–544PubMedGoogle Scholar
  26. 26.
    Blevins LS Jr, Clark RV, Owens DS (1998) Thromboembolic complications after inferior petrosal sinus sampling in patients with Cushing’s syndrome. Endocr Pract 4:365–367PubMedGoogle Scholar
  27. 27.
    Eljamel S (2003) New light on the brain; the rule of photosensitizing agents and laser light in the management of invasive intracranial tumours. Technol Cancer Res Treat 2:303–309PubMedGoogle Scholar
  28. 28.
    Grieb P (2004) 5-Aminolevulinic acid (ALA) and its applications in neurosurgery. Neurol Neurochir Pol 38:201–207PubMedGoogle Scholar
  29. 29.
    Stummer W, Pitchimeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomized controlled multicentre phase III trial. Lancet Oncol 7:392–401. doi: 10.1016/S1470-2045(06)70665-9 PubMedCrossRefGoogle Scholar
  30. 30.
    Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman A, Dorer DJ, Klibanski A, Biller BMK (2004) Diagnostic errors after inferior petrosal sinus sampling. J Clin Endocrinol Metab 89:3752–3763. doi: 10.1210/jc.2003-032249 PubMedCrossRefGoogle Scholar
  31. 31.
    Marks P (1999) Photodynamic therapy for central nervous system tumours; achievements and prospects. Br J Neurosurg 13:349–351. doi: 10.1080/02688699943439 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Department of NeurosurgeryNinewells Hospital and Medical SchoolDundeeScotland, UK
  2. 2.Department of EndocrinologyNinewells Hospital and Medical SchoolDundeeScotland, UK
  3. 3.Department of PhotobiologyNinewells Hospital and Medical SchoolDundeeScotland, UK

Personalised recommendations