Abstract
A prospective study was performed to evaluate the presentation, therapeutic management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs). In most of 385 consecutive patients, NFPAs were macroadenomas. The mean follow-up duration was 5.5 ± 1.4 years. Presentation was dominated by headache, visual disturbance, and hypopituitarism. Pituitary apoplexy (clinical and subclinical) was observed in 88 patients. Appropriate steroids replacement was given before surgery. Endoscope-assisted transsphenoidal surgery (TSS) was performed, and was well tolerated by all patients. At discharge, visual disturbances were improved in 215 (87.6%) patients who had complained of visual impairment preoperatively. The shorter the time from presentation of pituitary apoplexy to surgery, the better the outcome in visual function. Seventy-two (18.7%) patients developed transient diabetes insipidus (DI) and 85 (22.1%) patients developed hyponatremia, but all these improved within six weeks. Hypocortisolism was confirmed in 84 (21.8%) patients with an abnormal postoperative day 2 (POD2) 0800 serum cortisol level and in 122 (31.7%) patients with an abnormal POD6 0800 serum cortisol level. Hypothyroidism occurred in 135 (35.1%) patients. Steroids replacement was thus given immediately. Eight (2.1%) patients needed lifetime hormone substitution. No adrenal crisis occurred. Five (1.3%) patients died within six weeks. Residual tumors were confirmed in 79 patients (20.8%) by postoperative four-month enhanced MR imaging. Tumor recurrence or regrowth occurred in 56 patients (14.7%) during the follow-up period. These patients required repeat TSS or radiosurgery. The findings of this study support the use of TSS as a feasible initial treatment for NFPAs. With appropriate perioperative management of abnormal fluid, electrolyte, and endocrinological function, TSS was associated with minimum morbidity and was well tolerated by patients regardless of age. However, close screening of pituitary function and adequate neuroradiological follow-up should be performed after surgery for detection of tumor recurrence or regrowth. The indications for repeat TSS and postoperative radiosurgery in residual or recurrent NFPAs should be better defined.
Similar content being viewed by others
References
Agrawal D, Mahapatra AK (2005) Visual outcome of blind eyes in pituitary apoplexy after transsphenoidal surgery: a series of 14 eyes. Surg Neurol 63:42–46
Alameda C, Lucas T, Pineda E, Brito M, Uria JG, Magallon R, Estrada J, Barcelo B (2005) Experience in management of 51 non-functioning pituitary adenomas: indications for post-operative radiotherapy. J Endocrinol Investig 28:18–22
Aron DC, Howlett TA (2000) Pituitary incidentalomas. Endocrinol Metab Clin N Am 29:205–221
Ayuk J, McGregor EJ, Mitchell RD, Gittoes NJ (2004) Acute management of pituitary apoplexy-surgery or conservative management? Clin Endocrinol (Oxf) 61:747–752
Barzaghi LR, Losa M, Giovanelli M, Mortini P (2007) Complications of transsphenoidal surgery in patients with pituitary adenoma: experience at a single centre. Acta Neurochir (Wien) 149:877–885
Benbow SJ, Foy P, Jones B, Shaw D, MacFarlane IA (1997) Pituitary tumours presenting in the elderly: management and outcome. Clin Endocrinol (Oxf) 46:657–660
Bills DC, Meyer FB, Laws ER Jr, Davis DH, Ebersold MJ, Scheithauer BW, Ilstrup DM, Abboud CF (1993) A retrospective analysis of pituitary apoplexy. Neurosurgery 33:602–608
Brada M, Rajan B, Traish D, Ashley S, Holmes-Sellors PJ, Nussey S, Uttley D (1993) The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol (Oxf) 38:571–578
Breen P, Flickinger JC, Kondziolka D, Martinez AJ (1998) Radiotherapy for nonfunctional pituitary adenoma: analysis of long-term tumor control. J Neurosurg 89:933–938
Cappabianca P, Alfieri A, de Divitiis E (1998) Endoscopic endonasal transsphenoidal approach to the sella: towards functional endoscopic pituitary surgery (FEPS). Minim Invasive Neurosurg 41:66–73
Cappabianca P, Cavallo LM, de Divitiis E (2004) Endoscopic endonasal transsphenoidal surgery. Neurosurgery 55:933–940
Cardoso ER, Peterson EW (1984) Pituitary apoplexy: a review. Neurosurgery 14:363–373
Cavallo LM, Prevedello D, Esposito F, Laws ER Jr, Dusick JR, Messina A, Jane JA Jr, Kelly DF, Cappabianca P (2008) The role of the endoscope in the transsphenoidal management of cystic lesions of the sellar region. Neurosurg Rev 31:55–64
Chang EF, Zada G, Kim S, Lamborn KR, Quinones-Hinojosa A, Tyrrell JB, Wilson CB, Kunwar S (2008) Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas. J Neurosurg 108(4):736–745
Chanson P, Brochier S (2005) Non-functioning pituitary adenomas. J Endocrinol Investig 28(11 S):93–99
Chuang CC, Chang CN, Wei KC, Lao CC, Hsu PW, Huang YC, Chen YL, Lai LJ, Pai PC (2006) Surgical treatment of severe visual compromised patients after pituitary apoplexy. J Neurooncol 80:39–47
Comtois R, Beauregar H, Somma M, Serri O, Aris-Jilwan N, Hardy J (1991) The clinical and endocrine outcome to trans-sphenoidal microsurgery of non-secreting pituitary adenomas. Cancer 68:860–866
de Divitiis E, Cappabianca P, Cavallo M (2003) Endoscopic endonasal transsphenoidal approach to the sellar region. In: de Divitiis E, Cappabianca P (eds) Endoscopic endonasal. Transsphenoidal surgery. Springer, Wien, pp 91–130
Dekkers OM, Pereira AM, Roelfsema F, Voormolen JH, Neelis KJ, Schroijen MA, Smit JW, Romijn JA (2006) Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab 91:1796–1801
Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F, Schutte PJ, Smit JW, Romijn JA, Pereira AM (2007) The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol 156:217–224
Elsasser Imboden PN, De Tribolet N, Lobrinus A, Gaillard RC, Portmann L, Pralong F, Gomez F (2005) Apoplexy in pituitary macroadenoma: eight patients presenting in 12 months. Medicine (Baltim) 84:188–196
Fainstein Day P, Guitelman M, Artese R, Fiszledjer L, Chervin A, Vitale NM, Stalldecker G, De MV, Cornalo D, Alfieri A, Susana M, Gil M (2004) Retrospective multicentric study of pituitary incidentalomas. Pituitary 7:145–148
Ferrante L, Trillo G, Ramundo E, Celli P, Jaffrain-Rea ML, Salvati M, Esposito V, Roperto R, Osti MF, Minniti G (2002) Surgical treatment of pituitary tumors in the elderly: clinical outcome and long-term follow-up. J Neurooncol 60:185–191
Fries G, Perneczky A (1998) Endoscope-assisted brain surgery: part 2—analysis of 380 procedures. Neurosurgery 42:226–231
Gondim J, Schops M, Tella OI Jr (2003) Transnasal endoscopic surgery of the sellar region: study of the first 100 cases. Arq Neuropsiquiatr 61:836–841
Greenman Y, Ouaknine G, Veshchev I, Reider-Groswasser II, Segev Y, Stern N (2003) Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth. Clin Endocrinol (Oxf) 58:763–769
Jho HD (2001) Endoscopic transsphenoidal surgery. J Neurooncol 54:187–195
Jho HD, Carrau RL (1997) Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurgery 87:44–51
Jho HD, Carrau RL, Ko Y, Daly MA (1997) Endoscopic pituitary surgery: an early experience. Surg Neurol 7:213–223
Losa M, Mortini P, Barzaghi R, Franzin A, Giovanelli M (2001) Endocrine inactive and gonadotroph adenomas: diagnosis and management. J Neurooncol 54(2):167–177
Losa M, Mortini P, Barzaghi R, Ribotto P, Terreni MR, Marzoli SB, Pieralli S, Giovanelli M (2008) Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence. J Neurosurg 108(3):525–532
Minniti G, Esposito V, Piccirilli M, Fratticci A, Santoro A, Jaffrain-Rea ML (2005) Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature. Eur J Endocrinol 153:723–735
Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2005) Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab 90:800–804
Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2006) Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas. Clin Endocrinol (Oxf) 64:542–548
Minniti G, Jaffrain-Rea ML, Osti M, Cantore G, Enrici RM (2007) Radiotherapy for nonfunctioning pituitary adenomas: from conventional to modern stereotactic radiation techniques. Neurosurg Rev 30:167–175
Mohr G, Hardy J (1982) Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol 18:181–189
Molitch ME (2008) Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin N Am 37:151–171
Muacevic A, Uhl E (2004) Wowra B pituitary adenomas. Acta Neurochir Suppl 91:51–54
Muthukumar N, Rosette D, Soundaram M, Senthilbabu S, Badrinarayanan T (2008) Blindness following pituitary apoplexy: timing of surgery and neuro-ophthalmic outcome. J Clin Neurosci 15:873–879
Naidich MJ, Russell EJ (1999) Current approaches to imaging of the sellar region and pituitary. Endocrinol Metab Clin N Am 28:45–79
Nielsen EH, Lindholm J, Bjerre P, Christiansen JS, Hagen C, Juul S, Jørgensen J, Kruse A, Laurberg P (2006) Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma. Clin Endocrinol (Oxf) 64(3):319–322
Nomikos P, Ladar C, Fahlbusch R, Buchfelder M (2004) Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas—a study on 721 patients. Acta Neurochir (Wien) 146:27–35
Nomikos P, Buchfelder M, Fahlbusch R (2005) The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol 152:379–387
Oruçkaptan HH, Senmevsim O, Ozcan OE, Ozgen T (2000) Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol 53(3):211–219
Pamir MN, Kilic T, Belirgen M, Abacioglu U, Karabekiroglu N (2007) Pituitary adenomas treated with γ-knife radiosurgery: volumetric analysis of 100 cases with minimum 3 year follow-up. Neurosurgery 61:270–280
Parent AD (1990) Visual recovery after blindness from pituitary apoplexy. Can J Neurol Sci 17:88–91
Park P, Chandler WF, Barkan AL, Orrego JJ, Cowan JA, Griffith KA, Tsien C (2004) The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery 55:100–106
Perneczky A, Fries G (1998) Endoscope-assisted brain surgery: part 1—evolution, basic concept, and current technique. Neurosurgery 42:219–224
Philippon J (2004) Brain tumors in the elderly. Psychol Neuropsychiatr Vieil 2:29–33
Pollock BE, Cochran J, Natt N, Brown PD, Erickson D, Link MJ, Garces YI, Foote RL, Stafford SL, Schomberg PJ (2008) γ Knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience. Int J Radiat Oncol Biol Phys 70:1325–1329
Randeva HS, Schoebel J, Byrne J, Esiri M, Adams CB, Wass JA (1999) Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf) 51:181–188
Romijn JA, Smit JW, Lamberts SW (2003) Intrinsic imperfections of endocrine replacement therapy. Eur J Endocrinol 149:91–97
Sanno N, Oyama K, Tahara S, Teramoto A, Kato Y (2003) A survey of pituitary incidentaloma in Japan. Eur J Endocrinol 149:123–127
Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–407
Semple PL, Laws ER Jr (1999) Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing’s disease. J Neurosurg 91:175–179
Sheehan JP, Kondziolka D, Flickinger J, Lunsford LD (2002) Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg 97:408–414
Sheehan JP, Niranjan A, Sheehan JM, Jane JA Jr, Laws ER, Kondziolka D, Flickinger J, Landolt AM, Loeffler JS, Lunsford LD (2005) Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg 102:678–691
Sibal L, Ball SG, Connoly V, James RA, Kane P, Kelly WF, Kendall-Taylor P, Mathias D, Perros P, Quinton R, Vaidya B (2004) Pituitary apoplexy: a review of clinical presentation, management and outcome in 45 cases. Pituitary 7:157–163
Singer PA, Sevilla LJ (2003) Postoperative endocrine management of pituitary tumors. Neurosurg Clin N Am 14:123–138
Soto-Ares G, Cortet-Rudelli C, Assaker R, Boulinguez A, Dubest C, Dewailly D, Pruvo JP (2002) MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. Eur J Endocrinol 146:179–186
Tsang RW, Brierley JD, Panzarella T, Gospodarowicz MK, Sutcliffe SB, Simpson WJ (1994) Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 30:557–565
van Aken MO, Pereira AM, Biermasz NR, van Thiel SW, Hoftijzer HC, Smit JW, Roelfsema F, Lamberts SW, Romijn JA (2005) Quality of life in patients after long-term biochemical cure of Cushing’s disease. J Clin Endocrinol Metab 90:3279–3286
Verrees M, Arafah BM, Selman WR (2004) Pituitary tumor apoplexy. Characteristics, treatment and outcomes. Neurosurg Focus 16(4):E6
Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F (1999) Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab 84:3696–3700
Wichers-Rother M, Hoven S, Kristof RA, Bliesener N, Stoffel-Wagner B (2004) Non-functioning pituitary adenomas: endocrinological and clinical outcome after transsphenoidal and transcranial surgery. Exp Clin Endocrinol Diabetes 112:323–327
Woollons AC, Hunn MK, Rajapakse YR, Toomath R, Hamilton DA, Conaglen JV, Balakrishnan V (2000) Non-functioning pituitary adenomas: indications for postoperative radiotherapy. Clin Endocrinol (Oxf) 53:713–717
Zada G, Kelly DF, Cohan P, Wang C, Swerdloff R (2003) Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy, safety and patients impressions. J Neurosurg 98:350–358
Zayour DH, Selman WR, Arafah BM (2004) Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function. J Clin Endocrinol Metab 89:5649–5654
Acknowledgments
Part of this study was supported by the State Administration of Foreign Experts Affairs of China. Drs L. Chen, W.L. White, R.F. Spetzler and B. Xu have nothing to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, L., White, W.L., Spetzler, R.F. et al. A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome. J Neurooncol 102, 129–138 (2011). https://doi.org/10.1007/s11060-010-0302-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-010-0302-x