clinical article J Neurosurg 123:31–38, 2015
Endoscopic endonasal transsphenoidal surgery in elderly patients with pituitary adenomas *Jackson A. Gondim, MD,1 João Paulo Almeida, MD,2 Lucas Alverne F. de Albuquerque, MD,3 Erika Gomes, MD, PhD,4 Michele Schops, MD,5 and Jose Italo Mota, MD6 Departments of 1Neurosurgery, 4Otorhinolaryngology, and 6Endocrinology, General Hospital of Fortaleza; and 5Department of Anesthesiology, Universidade Federal do Ceará, Fortaleza, Ceara; 2Department of Neurosurgery, Campinas State University, Campinas, Sao Paulo; and 3Department of Neurosurgery, Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
Object With the increase in the average life expectancy, medical care of elderly patients with symptomatic pituitary adenoma (PA) will continue to grow. Little information exists in the literature about the surgical treatment of these patients. The aim of this study was to present the results of a single pituitary center in the surgical treatment of PAs in patients > 70 years of age. Methods In this retrospective study, 55 consecutive elderly patients (age ≥ 70 years) with nonfunctioning PAs underwent endoscopic transsphenoidal surgery at the General Hospital of Fortaleza, Brazil, between May 2000 and December 2012. The clinical and radiological results in this group were compared with 2 groups of younger patients: < 60 years (n = 289) and 60–69 years old (n = 30). Results Fifty-five patients ≥ 70 years of age (average age 72.5 years, range 70–84 years) underwent endoscopic surgery for treatment of PAs. The mean follow-up period was 50 months (range 12–144 months). The most common symptoms were visual impairment in 38 (69%) patients, headache in 16 (29%) patients, and complete ophthalmoplegia in 6 (10.9%). Elderly patients presented a higher incidence of ophthalmoplegia (p = 0.032) and a lower frequency of pituitary apoplexy before surgery (p < 0.05). Tumors with cavernous sinus invasion were treated surgically less frequently than in younger patients. Although patients with an American Society of Anesthesiologists score of 3 were more common in the elderly group (p < 0.05), no significant difference regarding surgical time, extent of resection, and hospitalization were observed. Elderly patients presented with more complications than patients < 60 years (32.7% vs 10%, p < 0.05). Complications observed in the elderly group included 5 CSF leaks (9%), 2 permanent diabetes insipidus cases (3.6%), 4 postoperative refractory hypertension cases (7.2%), 1 myocardial ischemia (1.8%), and 1 death (1.8%). Postoperative new anterior pituitary deficit was more common in the younger group (< 60 years old: 17.7%) than in the elderly (≥ 70 years old: 12.7%); however, there was no statistical difference. Conclusions Endoscopic transsphenoidal surgery for elderly patients with PAs may be associated with higher complication rates, especially secondary to early transitory complications, when compared with surgery performed in younger patients. Although the worst preoperative clinical status might be observed in this group, age alone is not associated with a worst final prognosis after endoscopic removal of nonfunctioning PAs. http://thejns.org/doi/abs/10.3171/2014.10.JNS14372
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Key Words pituitary adenomas; endoscopy; transsphenoidal; elderly; pituitary surgery
ife expectancy in developed countries increased by approximately 30 years during the 20th century, and continues to rise linearly.1,27,28 The population ≥ 60 years of age is currently increasing at the fastest pace ever (3.7% annually between 2010 and 2015), and is projected
to increase by 2.9% annually until 2050. Its numbers are expected to rise from 554 million in 2013 to 1.6 billion in 2050.41 Pituitary tumors are not unusual in patients > 70 years; this group represents up to 14% of all patients with pituitary tumors according to previous studies.7,8,21,23,24 As
Abbreviations ACTH = adrenocorticotropic hormone; ASA = American Society of Anesthesiologists; GH = growth hormone; PA = pituitary adenoma; PRL = prolactin; SIADH = syndrome of inappropriate antidiuretic hormone; TSH = thyroid-stimulating hormone. submitted February 18, 2014. accepted October 8, 2014. include when citing Published online April 3, 2015; DOI: 10.3171/2014.10.JNS14372. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. * Drs. Gondim, Almeida, Albuquerque, and Gomes contributed equally to this work. ©AANS, 2015
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the population increases and becomes older, the proportion of elderly patients in whom pituitary adenoma (PA) is diagnosed must continue to rise.34 Although elderly patients usually present a significant number of comorbidities and higher odds of postoperative complications when undergoing neurosurgical procedures, those with visual or neurological alterations or with symptoms secondary to hormonal dysfunction should be considered for surgical treatment.21,24 Previous studies have analyzed the outcomes in elderly patients who undergo transsphenoidal surgery for removal of PA, demonstrating the benefits of this approach in selected patients.2,6,17,22,24,41 When compared with microscopic transsphenoidal surgery, endoscopic endonasal approaches may be more aggressive, with exposure and resection of lateral extensions and manipulation of the suprasellar and parasellar regions, which is especially important in young patients with a long life expectancy, in contrast to the elderly. In such a way, endoscopic approaches, in theory, could lead to extended tumor resection but also to a higher risk of complications, such as carotid injury and CSF leaks in this group of patients. In this study we retrospectively analyzed the results of the treatment of PA in patients ≥ 70 years old who underwent endoscopic endonasal transsphenoidal surgery in our pituitary surgery center, focusing on the efficacy, safety, and outcomes associated with the surgical procedure in this population. Epidemiological, clinical, and radiological characteristics of this group were compared with the characteristics of younger patients with PA treated in our center. Additionally, we performed a detailed review of the literature regarding the treatment of PAs in the elderly population.
Methods
Study Design A retrospective analysis of patients who underwent endoscopic transsphenoidal resection of PAs between May 2000 and December 2012 in the Neuroendocrinology Department at the General Hospital of Fortaleza was performed. Although the definition of elderly varies in the literature (between 60 and 65 years old), the cutoff age we used was 70 years, because those patients are 1.61 times more prone to multiple morbidities compared with those between the ages of 60 and 65 years.41 Only nonfunctioning PAs were included for analysis, to reduce the impact of hypersecretory hormonal status in the clinical presentation and outcome as well as to validate our statistical analysis, because only 15 elderly patients presented with secreting tumors. Inclusion criteria were as follows: 1) patients diagnosed with nonfunctioning PA; 2) no previous surgical procedure for treatment of the lesions; and 3) surgical treatment via the transsphenoidal endoscopic approach in our department, by the senior author (J.A.G.). Patients with nonfunctioning PA were divided into 3 groups: elderly patients (≥70 years [n = 55]); patients 60–69 years (n = 30); and patients < 60 years (n = 289). All patients who did not fulfill the inclusion criteria and those without complete data regarding clinical follow-up were excluded from analysis. 32
J Neurosurg Volume 123 • July 2015
The institutional review board of the General Hospital of Fortaleza approved the study. All patients underwent neurological, ophthalmological, and endocrinological examinations before and after surgery. Pathology reports were reviewed for evaluation of hormonal status and evidence of hemorrhage or necrosis. The patients’ follow-up duration varied from 12 months to 10 years. Clinical and Endocrinological Assessment Endocrinological investigation was performed at our hospital. Multiple measurements of plasma growth hormone (GH), insulin-like growth factor–I, prolactin (PRL), free cortisol, thyroid-stimulating hormone (TSH), free thyroxin, luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels were studied. Endocrinological follow-up was routinely performed at 1 week, 3 months, and thereafter every 6 months. The preoperative comorbidity profile was evaluated according to the American Society of Anesthesiologists (ASA) Physical Status grading.31 Neuroradiological Studies A facial CT scan was used in all patients to evaluate the paranasal sinuses (septal anatomy, turbinate anatomy, sphenoidal, and maxillofacial format) for surgical planning. Preoperative MRI studies were performed in all patients, using a 1.5-T unit with T1- and T2-weighted spin echo before and after addition of Gd-based contrast medium. Follow-up MRI studies were obtained before hospital discharge, at 3 and 6 months after surgery, and then yearly. An independent neuroradiologist in our center evaluated all cases. Surgical Approach There was no significant difference regarding the technique used for the treatment of elderly patients. Details of the surgical technique used in our department have been previously described.15–17 Tumor Control The evaluation of the tumor resection was based on the analysis of the postoperative MRI studies obtained 3 and 6 months after surgery, and then every 12 months. Radiological evidence of no postoperative remnants was considered a total removal; otherwise the resection was considered subtotal.2,37 Statistical Analysis All data are expressed as the mean ± SD. The statistical software SPSS version 16.0 (SPSS Inc.) was used for data analysis. The Fisher test was used for evaluation of categorical data, with p < 0.05 considered statistically significant.
Results
Between May 2000 and December 2012, 603 patients (Table 1) underwent endoscopic transsphenoidal surgery for resection of PAs in the Neuroendocrinology Department of the General Hospital of Fortaleza, Brazil. The PAs
Pituitary adenomas in elderly patients
TABLE 1. Distribution of PAs according to age groups No. in Age Group Type of PA
Endoscopic endonasal transsphenoidal surgery in elderly patients with pituitary adenomas *Jackson A. Gondim, MD,1 João Paulo Almeida, MD,2 Lucas Alverne F. de Albuquerque, MD,3 Erika Gomes, MD, PhD,4 Michele Schops, MD,5 and Jose Italo Mota, MD6 Departments of 1Neurosurgery, 4Otorhinolaryngology, and 6Endocrinology, General Hospital of Fortaleza; and 5Department of Anesthesiology, Universidade Federal do Ceará, Fortaleza, Ceara; 2Department of Neurosurgery, Campinas State University, Campinas, Sao Paulo; and 3Department of Neurosurgery, Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
Object With the increase in the average life expectancy, medical care of elderly patients with symptomatic pituitary adenoma (PA) will continue to grow. Little information exists in the literature about the surgical treatment of these patients. The aim of this study was to present the results of a single pituitary center in the surgical treatment of PAs in patients > 70 years of age. Methods In this retrospective study, 55 consecutive elderly patients (age ≥ 70 years) with nonfunctioning PAs underwent endoscopic transsphenoidal surgery at the General Hospital of Fortaleza, Brazil, between May 2000 and December 2012. The clinical and radiological results in this group were compared with 2 groups of younger patients: < 60 years (n = 289) and 60–69 years old (n = 30). Results Fifty-five patients ≥ 70 years of age (average age 72.5 years, range 70–84 years) underwent endoscopic surgery for treatment of PAs. The mean follow-up period was 50 months (range 12–144 months). The most common symptoms were visual impairment in 38 (69%) patients, headache in 16 (29%) patients, and complete ophthalmoplegia in 6 (10.9%). Elderly patients presented a higher incidence of ophthalmoplegia (p = 0.032) and a lower frequency of pituitary apoplexy before surgery (p < 0.05). Tumors with cavernous sinus invasion were treated surgically less frequently than in younger patients. Although patients with an American Society of Anesthesiologists score of 3 were more common in the elderly group (p < 0.05), no significant difference regarding surgical time, extent of resection, and hospitalization were observed. Elderly patients presented with more complications than patients < 60 years (32.7% vs 10%, p < 0.05). Complications observed in the elderly group included 5 CSF leaks (9%), 2 permanent diabetes insipidus cases (3.6%), 4 postoperative refractory hypertension cases (7.2%), 1 myocardial ischemia (1.8%), and 1 death (1.8%). Postoperative new anterior pituitary deficit was more common in the younger group (< 60 years old: 17.7%) than in the elderly (≥ 70 years old: 12.7%); however, there was no statistical difference. Conclusions Endoscopic transsphenoidal surgery for elderly patients with PAs may be associated with higher complication rates, especially secondary to early transitory complications, when compared with surgery performed in younger patients. Although the worst preoperative clinical status might be observed in this group, age alone is not associated with a worst final prognosis after endoscopic removal of nonfunctioning PAs. http://thejns.org/doi/abs/10.3171/2014.10.JNS14372
L
Key Words pituitary adenomas; endoscopy; transsphenoidal; elderly; pituitary surgery
ife expectancy in developed countries increased by approximately 30 years during the 20th century, and continues to rise linearly.1,27,28 The population ≥ 60 years of age is currently increasing at the fastest pace ever (3.7% annually between 2010 and 2015), and is projected
to increase by 2.9% annually until 2050. Its numbers are expected to rise from 554 million in 2013 to 1.6 billion in 2050.41 Pituitary tumors are not unusual in patients > 70 years; this group represents up to 14% of all patients with pituitary tumors according to previous studies.7,8,21,23,24 As
Abbreviations ACTH = adrenocorticotropic hormone; ASA = American Society of Anesthesiologists; GH = growth hormone; PA = pituitary adenoma; PRL = prolactin; SIADH = syndrome of inappropriate antidiuretic hormone; TSH = thyroid-stimulating hormone. submitted February 18, 2014. accepted October 8, 2014. include when citing Published online April 3, 2015; DOI: 10.3171/2014.10.JNS14372. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. * Drs. Gondim, Almeida, Albuquerque, and Gomes contributed equally to this work. ©AANS, 2015
J Neurosurg Volume 123 • July 2015
31
J. A. Gondim et al.
the population increases and becomes older, the proportion of elderly patients in whom pituitary adenoma (PA) is diagnosed must continue to rise.34 Although elderly patients usually present a significant number of comorbidities and higher odds of postoperative complications when undergoing neurosurgical procedures, those with visual or neurological alterations or with symptoms secondary to hormonal dysfunction should be considered for surgical treatment.21,24 Previous studies have analyzed the outcomes in elderly patients who undergo transsphenoidal surgery for removal of PA, demonstrating the benefits of this approach in selected patients.2,6,17,22,24,41 When compared with microscopic transsphenoidal surgery, endoscopic endonasal approaches may be more aggressive, with exposure and resection of lateral extensions and manipulation of the suprasellar and parasellar regions, which is especially important in young patients with a long life expectancy, in contrast to the elderly. In such a way, endoscopic approaches, in theory, could lead to extended tumor resection but also to a higher risk of complications, such as carotid injury and CSF leaks in this group of patients. In this study we retrospectively analyzed the results of the treatment of PA in patients ≥ 70 years old who underwent endoscopic endonasal transsphenoidal surgery in our pituitary surgery center, focusing on the efficacy, safety, and outcomes associated with the surgical procedure in this population. Epidemiological, clinical, and radiological characteristics of this group were compared with the characteristics of younger patients with PA treated in our center. Additionally, we performed a detailed review of the literature regarding the treatment of PAs in the elderly population.
Methods
Study Design A retrospective analysis of patients who underwent endoscopic transsphenoidal resection of PAs between May 2000 and December 2012 in the Neuroendocrinology Department at the General Hospital of Fortaleza was performed. Although the definition of elderly varies in the literature (between 60 and 65 years old), the cutoff age we used was 70 years, because those patients are 1.61 times more prone to multiple morbidities compared with those between the ages of 60 and 65 years.41 Only nonfunctioning PAs were included for analysis, to reduce the impact of hypersecretory hormonal status in the clinical presentation and outcome as well as to validate our statistical analysis, because only 15 elderly patients presented with secreting tumors. Inclusion criteria were as follows: 1) patients diagnosed with nonfunctioning PA; 2) no previous surgical procedure for treatment of the lesions; and 3) surgical treatment via the transsphenoidal endoscopic approach in our department, by the senior author (J.A.G.). Patients with nonfunctioning PA were divided into 3 groups: elderly patients (≥70 years [n = 55]); patients 60–69 years (n = 30); and patients < 60 years (n = 289). All patients who did not fulfill the inclusion criteria and those without complete data regarding clinical follow-up were excluded from analysis. 32
J Neurosurg Volume 123 • July 2015
The institutional review board of the General Hospital of Fortaleza approved the study. All patients underwent neurological, ophthalmological, and endocrinological examinations before and after surgery. Pathology reports were reviewed for evaluation of hormonal status and evidence of hemorrhage or necrosis. The patients’ follow-up duration varied from 12 months to 10 years. Clinical and Endocrinological Assessment Endocrinological investigation was performed at our hospital. Multiple measurements of plasma growth hormone (GH), insulin-like growth factor–I, prolactin (PRL), free cortisol, thyroid-stimulating hormone (TSH), free thyroxin, luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels were studied. Endocrinological follow-up was routinely performed at 1 week, 3 months, and thereafter every 6 months. The preoperative comorbidity profile was evaluated according to the American Society of Anesthesiologists (ASA) Physical Status grading.31 Neuroradiological Studies A facial CT scan was used in all patients to evaluate the paranasal sinuses (septal anatomy, turbinate anatomy, sphenoidal, and maxillofacial format) for surgical planning. Preoperative MRI studies were performed in all patients, using a 1.5-T unit with T1- and T2-weighted spin echo before and after addition of Gd-based contrast medium. Follow-up MRI studies were obtained before hospital discharge, at 3 and 6 months after surgery, and then yearly. An independent neuroradiologist in our center evaluated all cases. Surgical Approach There was no significant difference regarding the technique used for the treatment of elderly patients. Details of the surgical technique used in our department have been previously described.15–17 Tumor Control The evaluation of the tumor resection was based on the analysis of the postoperative MRI studies obtained 3 and 6 months after surgery, and then every 12 months. Radiological evidence of no postoperative remnants was considered a total removal; otherwise the resection was considered subtotal.2,37 Statistical Analysis All data are expressed as the mean ± SD. The statistical software SPSS version 16.0 (SPSS Inc.) was used for data analysis. The Fisher test was used for evaluation of categorical data, with p < 0.05 considered statistically significant.
Results
Between May 2000 and December 2012, 603 patients (Table 1) underwent endoscopic transsphenoidal surgery for resection of PAs in the Neuroendocrinology Department of the General Hospital of Fortaleza, Brazil. The PAs
Pituitary adenomas in elderly patients
TABLE 1. Distribution of PAs according to age groups No. in Age Group Type of PA
