J Neurosurg 121:527–535, 2014 ©AANS, 2014
Descriptive epidemiology of pituitary tumors in the United States, 2004–2009 Clinical article Haley Gittleman, M.S.,1,2 Quinn T. Ostrom, M.A., M.P.H.,1,2 Paul D. Farah, B.S., 3 Annie Ondracek, 4 Yanwen Chen, Ph.D.,1,2 Yingli Wolinsky, Ph.D.,1,2 Carol Kruchko, B.A., 2 Justin Singer, M.D., 5 Varun R. Kshettry, M.D., 6 Edward R. Laws, M.D.,7 Andrew E. Sloan, M.D., 5 Warren R. Selman, M.D., 5 and Jill S. Barnholtz-Sloan, Ph.D.1,2 Brain Tumor and Neuro-Oncology Center, Department of Neurosurgery, University Hospitals Case Medical Center; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine; 3Case Western Reserve University; 6Department of Neurosurgery, Neurological and Taussig Cancer Institute, Cleveland Clinic, Cleveland; 4 The Ohio State University, Columbus, Ohio; 2Central Brain Tumor Registry of the United States, Hinsdale, Illinois; and 7Department of Neurological Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 5 1
Object. Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009. Methods. Using incidence data from 49 population-based state cancer registries, 2004–2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined. Results. The overall annual incidence rate increased from 2.52 (95% CI 2.46–2.58) in 2004 to 3.13 (95% CI 3.07–3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%–5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33–2.50) to 2.94 (95% CI 2.85–3.03) in men and 2.70 (95% CI 2.62–2.79) to 3.40 (95% CI 3.31–3.49) in women, with APCs of 4.35% (95% CI 3.21%–5.51%) and 4.34% (95% CI 2.23%–6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25–2.37) to 2.81 (95% CI 2.74–2.88) in whites, 3.99 (95% CI 3.77–4.23) to 5.31 (95% CI 5.06–5.56) in blacks, 1.77 (95% CI 1.26–2.42) to 2.52 (95% CI 1.96–3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62–2.13) to 2.03 (95% CI 1.80–2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%–4.95%), 5.25% (95% CI 3.19%–7.36%), 5.31% (95% CI -0.11% to 11.03%), and 2.40% (95% CI -3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40–2.52) to 3.03 (95% CI 2.97–3.10) in non-Hispanics and 3.12 (95% CI 2.91–3.34) to 4.01 (95% CI 3.80–4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%–5.65%) and 5.01% (95% CI 4.42%–5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years old and lowest for those 15–24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24–6.54) and 1.56 (95% CI 1.51–1.61), respectively. Conclusions. In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population. (http://thejns.org/doi/abs/10.3171/2014.5.JNS131819)
Key Words • pituitary tumor • overall incidence • incidence trend • epidemiology • CBTRUS • pituitary surgery
Abbreviations used in this paper: AIAN = American Indian or Alaska Native; APC = annual percentage change; API = Asian or Pacific Islander; CBTRUS = Central Brain Tumor Registry of the United States; CDC = Centers for Disease Control and Prevention; ICD-O-3 = International Classification of Diseases for Oncology, Third Edition; NPCR = National Program of Cancer Registries; SEER = Surveillance, Epidemiology, and End Results.
J Neurosurg / Volume 121 / September 2014
P
ituitary tumors are abnormal growths that develop in the pituitary gland and are generally benign slowgrowing tumors. Although most are not symptomatic, they can cause a wide array of symptoms depending on
This article contains some figures that are displayed in color online but in black-and-white in the print edition.
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H. Gittleman et al. their hormonal activity. Even those that are not hormone secreting can cause symptoms as a result of intracranial mass effect. Tumor growth appears to be promoted by hormones that modulate normal pituitary activity and by growth factors that have been implicated in normal fetal pituitary development.1 More specifically, tumors of the pituitary seem to arise from the expansion of single precursor cells that possess a unique proliferative advantage.9 At least one-third of pituitary tumors can cause health complications that may include mood disorders, sexual dysfunction, infertility, obesity and disfigurement, visual disturbances, hypertension, diabetes mellitus, and accelerated heart disease.1 The overall age-adjusted incidence rate of pituitary tumors has been reported by the Central Brain Tumor Registry of the United States (CBTRUS) as 2.94 cases per 100,000 persons.4 After gliomas and meningiomas, tumors of the pituitary are the third most common brain tumor, accounting for 10%–15% of all primary brain tumors.15 A comprehensive meta-analysis of data from autopsy and radiological studies suggested that pituitary tumors may be present in as many as 1 in every 6 persons.3,5 More specifically, Ezzat et al. reported that pituitary adenomas occurred with a frequency of 14.4% in pooled autopsy series and 22.5% in radiological series.5 In the present report we describe the epidemiology of pituitary tumors, focusing on incidence rates by patient sex, race, Hispanic ethnicity, and age at diagnosis as well as diagnostic confirmation by subregion of the US by using data from two populationbased cancer registries that include cases of malignant and nonmalignant primary brain and CNS tumors.
Data Collection
Methods
We used population-based registry data on cases diagnosed with pituitary tumors between 2004 and 2009. The CBTRUS contains incidence data from 49 central cancer registries (Centers for Disease Control and Prevention’s [CDC’s] 44 National Program of Cancer Registries [NPCR] and 5 Surveillance, Epidemiology, and End Results [SEER] registries) and captures the incidence of primary brain tumors for over 97% of the US population (CBTRUS 2012). The Benign Brain Tumor Cancer Registries Amendment Act, which mandated registration of benign brain tumors in the US, went into effect in 2004; hence, we conducted all analyses using 2004–2009 data to allow for the most complete data set. Our analysis includes newly diagnosed malignant and nonmalignant tumors with International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 (Table 1). Population data for each region were obtained from the National Cancer Institute’s SEER program (http://seer. cancer.gov) and were made available by the US Census Bureau.
Statistical Analysis
SEER*Stat (http://seer.cancer.gov/seerstat/) was used
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to calculate frequencies and incidence rates overall and by patient sex, race, Hispanic ethnicity, selected age groups, and year of diagnosis. The standard population used to calculate the age-adjusted incidence rates is an estimate of the 2000 US population. Frequency of diagnostic confirmation by subregion of the US was calculated with SEER*Stat as well, using the North American Association of Central Cancer Registries (NAACCR) regional scheme (http://faststats.naaccr.org). Diagnostic confirmation records the best method used to confirm the presence of the cancer being reported. The best method could be used at any time throughout the entire course of the disease; it is not limited to confirmation at the time of initial diagnosis. Joinpoint regression software was used to identify sharp changes in incidence during the time period included in this analysis (http://surveillance.cancer.gov/joinpoint/). This statistical software takes trend data and fits the simplest Joinpoint model that the data allow.
Results
Average Annual Incidence Trends
The CBTRUS data set included 51,125 cases of pituitary tumors diagnosed from 2004 to 2009. The distribution of benign versus malignant tumors was 99.7% versus 0.3%. All age-adjusted incidence rates were reported per 100,000 population. The overall age-adjusted incidence of pituitary tumor was 2.87 (Table 2). When stratifying by patient sex, the overall age-adjusted incidence of pituitary tumor was 2.71 for males and 3.11 for females (Table 3). When stratifying by race, the overall age-adjusted incidence of pituitary tumor was 2.59 for whites, 4.76 for blacks, 2.28 for American Indians or Alaska Natives (AIANs), and 2.13 for Asian or Pacific Islanders (APIs; Table 4). When stratifying by Hispanic ethnicity, the overall age-adjusted incidence of pituitary tumor was 2.79 for non–Spanish-Hispanic-Latinos and 3.55 for SpanishHispanic-Latinos (Table 5). When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years of age and lowest for those 15–24 years of age, with corresponding overall age-adjusted incidence rates of 6.39 and 1.56, respectively (Table 6).
Time Trends
In the period from 2004 to 2009, the overall annual percentage change (APC) was 4.25% (95% CI 2.91%– 5.61%), and the annual age-adjusted incidence rates for pituitary tumor ranged from 2.52 to 3.13 (Fig. 1 and Table 2). When stratifying by patient sex, the APC was 4.35% (95% CI 3.21%–5.51%) for males and 4.34% (95% CI 2.23%–6.49%) for females (Fig. 2 and Table 3). The annual age-adjusted incidence rates for pituitary tumor ranged from 2.42 to 2.94 in males and 2.70 to 3.40 in females. When stratifying by race, the APC was 3.91% (95% CI 2.88%–4.95%) for whites, 5.25% (95% CI 3.19%–7.36%) for blacks, 5.31% (95% CI -0.11% to 11.03%) for AIANs, and 2.40% (-3.20% to 8.31%) for APIs (Table 4). The annual age-adjusted rates for pituitary tumor ranged from 2.31 to 2.81 in whites, 3.99 to 5.31 in blacks, 1.77 to 2.52 in AIANs, and 1.86 to 2.03 in APIs. When stratifying by Hispanic ethnicity, the APC was 4.15% (95% CI 2.67%– J Neurosurg / Volume 121 / September 2014
Epidemiology of pituitary tumors in the US, 2004–2009 TABLE 1: Brain and CNS tumors of the pituitary gland (CBTRUS, 2004–2009)* ICD-O Topography Code & Histology Grouping ICD-O-3 Histology Code C75.1 & C75.2 tumorlet adenocarcinoma, NOS
8040 8140
8290 8300 8310 8323
tumorlet, benign; tumorlet, NOS adenoma, NOS; atypical adenoma; adenocarcinoma in situ; adenocarcinoma, NOS monomorphic adenoma neuroendocrine carcinoma, NOS papillary adenoma, NOS chromophobe adenoma; chromophobe carcinoma prolactinoma pituitary adenoma, NOS; pituitary carcinoma, NOS acidophil adenoma; acidophil carcinoma mixed acidophil-basophil adenoma; mixed acidophil-basophil carcinoma oxyphilic adenoma; oxyphilic adenocarcinoma basophil adenoma; basophil carcinoma clear cell adenoma; clear cell adenocarcinoma, NOS mixed cell adenoma; mixed cell adenocarcinoma
9492
gangliocytoma
9582
granular cell tumor of sellar region
8146 8246 8260 8270 8271 8272 8280 8281
neuroendocrine carcinoma, NOS papillary adenoma, NOS chromophobe carcinoma prolactinoma pituitary adenoma & carcinoma acidophil carcinoma
oxyphilic adenocarcinoma basophil carcinoma clear cell adenocarcinoma, NOS granular cell carcinoma C75.1 only ganglioneuroblastoma C75.1 & C75.2 granular cell tumors
Specific Histology Classification
* NOS = not otherwise specified.
5.65%) for non–Spanish-Hispanic-Latinos and 5.01% (95% CI 4.42%–5.60%) for Spanish-Hispanic-Latinos (Table 5). The annual age-adjusted rates for pituitary tumor ranged from 2.46 to 3.03 in non–Spanish-Hispanic-Latinos and 3.12 to 4.01 in Spanish-Hispanic-Latinos. When stratifying by age at diagnosis, the APC was 3.56% (95% CI 0.57%–6.65%) for 15- to 24-year-olds, 4.14% (95% CI 1.85%–6.47%) for 25- to 34-year-olds, 6.22% (95% CI 4.53%–7.95%) for 35- to 44-year-olds, 4.34% (95% CI 3.77%–4.92%) for 45- to 54-year-olds, 3.62% (95% CI 2.09%–5.18%) for 55- to 64-year-olds, 2.99% (95% CI 0.30%–5.76%) for 65- to 74-year-olds, 4.55% (95% CI 2.99%–6.13%) for 75- to 84-year-olds, and 6.05% (95% CI TABLE 2: Age-adjusted incidence rates and APC in incidence of pituitary tumors (CBTRUS, 2004–2009)* Year
No. of Cases
AAIR
95% CI
APC (95% CI)†
overall 2004 2005 2006 2007 2008 2009
51,125 7243 7811 8485 8722 9266 9598
2.87 2.52 2.69 2.88 2.92 3.07 3.13
2.85–2.90 2.46–2.58 2.63–2.75 2.82–2.94 2.86–2.98 3.01–3.14 3.07–3.20
4.25 (2.91–5.61)
* AAIR = age-adjusted incidence rate. † Values expressed as percent.
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-0.51% to 13.05%) for those 85 years and older (Table 6). The annual age-adjusted rates for pituitary tumor ranged from 1.37 to 1.74 in the 15- to 24-year-olds, from 2.47 to 3.04 in the 25- to 34-year-olds, from 2.81 to 3.81 in the TABLE 3: Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by patient sex (CBTRUS, 2004–2009) Year male overall 2004 2005 2006 2007 2008 2009 female overall 2004 2005 2006 2007 2008 2009
No. of Cases
AAIR
95% CI
APC (95% CI)*
22,993 3265 3476 3690 3966 4261 4335
2.71 2.42 2.53 2.64 2.78 2.95 2.94
2.68–2.75 2.33–2.50 2.45–2.62 2.55–2.73 2.70–2.87 2.86–3.04 2.85–3.03
4.35 (3.21–5.51)
28,132 3978 4335 4795 4756 5005 5263
3.11 2.70 2.92 3.20 3.14 3.28 3.40
3.07–3.14 2.62–2.79 2.83–3.00 3.11–3.29 3.05–3.23 3.18–3.37 3.31–3.49
4.34 (2.23–6.49)
* Values expressed as percent.
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H. Gittleman et al. TABLE 4: Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by race (CBTRUS, 2004–2009) Years white overall 2004 2005 2006 2007 2008 2009 black overall 2004 2005 2006 2007 2008 2009 AIAN overall 2004 2005 2006 2007 2008 2009 API overall 2004 2005 2006 2007 2008 2009
No. of Cases
AAIR
95% CI
APC (95% CI)*
38,121 5531 5856 6320 6491 6849 7074
2.59 2.31 2.43 2.59 2.63 2.75 2.81
2.56–2.61 3.91 (2.88–4.95) 2.25–2.37 2.36–2.49 2.52–2.65 2.56–2.69 2.68–2.82 2.74–2.88
9294 1238 1390 1553 1595 1688 1830
4.76 3.99 4.44 4.81 4.86 5.09 5.31
4.66–4.86 5.25 (3.19–7.36) 3.77–4.23 4.20–4.69 4.57–5.06 4.62–5.11 4.84–5.34 5.06–5.56
396 45 67 66 69 73 76
2.28 1.77 2.27 2.37 2.24 2.54 2.52
2.05–2.54 5.31 (−0.11 to 11.03) 1.26–2.42 1.73–2.92 1.80–3.06 1.73–2.87 1.95–3.23 1.96–3.19
1700 227 256 285 306 331 295
2.13 1.86 2.05 2.19 2.26 2.37 2.03
2.02–2.23 2.40 (−3.20 to 8.31) 1.62–2.13 1.80–2.33 1.94–2.47 2.00–2.53 2.12–2.65 1.80–2.28
* Values expressed as percent.
35- to 44-year-olds, from 3.43 to 4.29 in the 45- to 54-yearolds, from 4.29 to 5.10 in the 55- to 64-year-olds, from 5.66 to 6.73 in the 65- to 74-year-olds, from 5.41 to 6.66 in the 75- to 84-year-olds, and from 2.99 to 4.43 in those 85 years and older . Incidence by Age at Diagnosis and Patient Sex
When stratifying by age at diagnosis and patient sex, females had a greater incidence of pituitary tumors from ages 0 to 50 years (Fig. 3). From ages 50 to 54 years, the incidence rates were similar between males (4.25) and females (3.99; Table 7). After age 54 years, males had a greater incidence of pituitary tumors.
Diagnostic Confirmation
Across the US, the majority of pituitary tumors were
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TABLE 5: Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by Hispanic ethnicity (CBTRUS, 2004–2009) Year
No. of Cases
AAIR
non–Spanish-Hispanic-Latino overall 43,880 2.79 2004 6287 2.46 2005 6742 2.62 2006 7314 2.81 2007 7496 2.85 2008 7926 3.00 2009 8115 3.03 Spanish-Hispanic-Latino overall 7245 3.55 2004 956 3.12 2005 1069 3.28 2006 1171 3.45 2007 1226 3.57 2008 1340 3.76 2009 1483 4.01
95% CI
APC (95% CI)*
2.77–2.82 2.40–2.52 2.55–2.68 2.74–2.87 2.78–2.91 2.93–3.06 2.97–3.10
4.15 (2.67–5.65)
3.47–3.64 2.91–3.34 3.07–3.51 3.24–3.67 3.35–3.79 3.55–3.99 3.80–4.24
5.01 (4.42–5.60)
* Values expressed as percent.
microscopically confirmed (Fig. 4), which include those tumors with a positive histology or positive cytology. The biggest difference in diagnostic confirmation was in the New England subregion, where 75% were microscopically confirmed and 25% were radiographically confirmed. Tumors that were radiographically confirmed involved radiology and other imaging techniques without microscopic confirmation. The smallest difference in diagnostic confirmation was in the West South Central subregion, where 54% were microscopically confirmed and 46% were radiographically confirmed.
Discussion
Pituitary tumors are relatively common in the US, with an average incidence of 2.9 per 100,000 population between 2004 and 2009, and this incidence is rising with an overall APC of 4.25%. This increase supports results found in other population-based studies. In a cohort study conducted in northern Finland, the incidence of pituitary adenomas increased from 3.8 to 4.2 cases per 100,000 population in 1992–1999 to 2000–2007.14 The increase in incidence was attributable to the rise in incidentally discovered pituitary adenomas from 0.59 to 1.6 cases per 100,000 population.14 In Sweden, a cohort study utilizing their nationwide cancer registry revealed that the agestandardized incidence of pituitary adenoma increased from approximately 6 to 11 cases per million inhabitants from 1958 to 1991.11 Rises in incidence have generally been attributed to improvements in diagnostic technology that have increased sensitivity for detecting pituitary tumors.7 In addition, the greater use of imaging, particularly for indications such as sinusitis, trauma, and headache, may lead to the increased detection of incidental pituitary J Neurosurg / Volume 121 / September 2014
Epidemiology of pituitary tumors in the US, 2004–2009 TABLE 6: Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by age at diagnosis (CBTRUS, 2004–2009) Years
No. of Cases
ages 15–24 yrs overall 2004 2005 2006 2007 2008 2009 ages 25–34 yrs overall 2004 2005 2006 2007 2008 2009 ages 35–44 yrs overall 2004 2005 2006 2007 2008 2009 ages 45–54 yrs overall 2004 2005 2006 2007 2008 2009 ages 55–64 yrs overall 2004 2005 2006 2007 2008 2009 ages 65–74 yrs overall 2004 2005 2006 2007 2008 2009
AAIR
95% CI
APC (95% CI)*
3905 566 629 663 657 650 740
1.56 1.37 1.52 1.59 1.56 1.55 1.74
(1.51–1.61) (1.26–1.49) (1.40–1.64) (1.47–1.72) (1.44–1.68) (1.43–1.67) (1.62–1.87)
3.56 (0.57–6.65)
6576 950 998 1120 1111 1179 1218
2.82 2.47 2.61 2.91 2.86 3.00 3.04
(2.75–2.89) (2.32–2.64) (2.45–2.77) (2.74–3.09) (2.69–3.03) (2.83–3.18) (2.87–3.21)
4.14 (1.85–6.47)
8412 1202 1321 1383 1421 1542 1543
3.36 2.81 3.12 3.28 3.41 3.76 3.81
(3.29–3.44) (2.66–2.98) (2.95–3.29) (3.11–3.46) (3.24–3.59) (3.58–3.95) (3.63–4.01)
6.22 (4.53–7.95)
9777 1382 1498 1598 1677 1765 1857
3.87 3.43 3.64 3.81 3.93 4.08 4.29
(3.79–3.95) (3.26–3.62) (3.45–3.83) (3.63–4.00) (3.75–4.13) (3.90–4.28) (4.09–4.49)
4.34 (3.77–4.92)
8796 1203 1268 1466 1525 1610 1724
4.72 4.29 4.33 4.79 4.80 4.94 5.10
(4.62–4.82) (4.05–4.54) (4.09–4.57) (4.54–5.04) (4.56–5.04) (4.70–5.19) (4.86–5.35)
3.62 (2.09–5.18)
7220 1017 1102 1212 1241 1307 1341
6.39 5.66 6.07 6.60 6.61 6.73 6.62
(6.24–6.54) (5.31–6.02) (5.72–6.44) (6.24–6.99) (6.25–6.99) (6.36–7.10) (6.27–6.99)
2.99 (0.30–5.76)
(continued)
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TABLE 6: Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by age at diagnosis (CBTRUS, 2004–2009) (continued) Years
No. of Cases AAIR
ages 75–84 yrs overall 4632 2004 687 2005 717 2006 762 2007 767 2008 854 2009 845 ages ≥85 yrs overall 1175 2004 136 2005 179 2006 176 2007 223 2008 235 2009 226
95% CI
APC (95% CI)*
6.05 5.41 5.62 5.95 6.02 6.66 6.65
(5.88–6.23) 4.55 (2.99–6.13) (5.02–5.83) (5.21–6.04) (5.53–6.39) (5.60–6.47) (6.22–7.12) (6.21–7.12)
3.90 2.99 3.79 3.57 4.35 4.43 4.12
(3.68–4.13) 6.05 (−0.51 to 13.05) (2.50–3.53) (3.25–4.38) (3.07–4.14) (3.80–4.96) (3.88–5.03) (3.60–4.70)
* Values expressed as percent.
tumors. In fact, the prevalence of asymptomatic incidental pituitary tumors in the general population has been estimated between 0.15% and 0.3%.10,16 Furthermore, greater accuracy and improved documentation of pituitary tumors in cancer registries may be responsible for the observed increase in incidence. Nonetheless, these results may also represent a true increase in pituitary tumor incidence. Our analysis demonstrated an increased risk for pituitary tumor as one ages, with the peak incidence occurring between 65 and 74 years old. Incidence was slightly higher in females than in males. The male/female incidence rate ratio was 0.87, with incidence peaks of 4.37 and 5.19 in females at ages 30–34 and 70–74 years, respectively (Fig. 3; Table 7). In males, one large incidence peak of 8.46 at ages 75–79 years was found. This difference was attributable to prolactinomas, the most commonly diagnosed pituitary tumor, which occur more frequently in women than in men and at earlier ages in women than in men.2,6,7 Moreover, females tend to present earlier because of an increased symptom burden from hyperprolactinemia, such as a disruption in the menstrual period and hypogonadism.2 Additionally, pituitary tumors were detected more frequently in women than in men.12,13 These factors may account for females having a peak incidence at a significantly younger age than that in males.7 An analysis of SEER data by McDowell and colleagues revealed that the age-adjusted incidence rate of pituitary adenomas per 100,000 population in blacks was 4.4, which was much higher than in AIANs, APIs, and whites, whose incidence rates were 1.9, 2.3, and 2.5, respectively (p < 0.001).8 This finding is consistent with current findings; that is, the average incidence for whites and blacks was 2.6 and 4.8, respectively. Reasons for this disparity include a natural difference in incidence as well as 531
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Fig. 1. Overall average annual age-adjusted time trend of pituitary tumors (CBTRUS, 2004–2009).
Fig. 2. Average annual age-adjusted incidence rates of pituitary tumors, by patient sex (CBTRUS, 2004–2009).
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Epidemiology of pituitary tumors in the US, 2004–2009
Fig. 3. Average age-adjusted incidence rates of pituitary tumors, by age at diagnosis and patient sex (CBTRUS, 2004–2009). TABLE 7: Average age-adjusted incidence rates of pituitary tumors, by age at diagnosis and patient sex (CBTRUS, 2004–2009) Male
Female
Age (yrs)
No. of Cases
AAIR
95% CI
No. of Cases
AAIR
95% CI
0–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85
237 383 508 780 1036 1415 1797 2148 2518 2548 2376 2234 1926 1563 991 533
0.13 0.60 0.79 1.28 1.78 2.31 2.80 3.29 4.25 5.01 6.09 7.65 8.43 8.46 7.62 5.72
0.11–0.15 0.54–0.66 0.72–0.86 1.19–1.37 1.67–1.89 2.19–2.44 2.67–2.93 3.16–3.44 4.09–4.42 4.81–5.21 5.84–6.34 7.34–7.97 8.06–8.82 8.04–8.89 7.16–8.11 5.24–6.22
395 1200 1814 2278 2482 2539 2661 2671 2440 2114 1758 1612 1448 1180 898 642
0.23 1.98 3.00 3.88 4.37 4.21 4.14 4.01 3.99 3.93 4.12 4.84 5.19 4.73 4.39 3.09
0.20–0.25 1.87–2.10 2.87–3.14 3.73–4.05 4.20–4.55 4.05–4.38 3.98–4.30 3.86–4.17 3.83–4.15 3.76–4.10 3.93–4.31 4.60–5.08 4.93–5.47 4.46–5.01 4.11–4.69 2.85–3.34
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Fig. 4. Diagnostic confirmation of pituitary tumors, by US subregion. Frequencies are listed inside the bars (CBTRUS, 2004– 2009).
the fact that blacks may present with different symptoms or present with symptoms at different timings.8 The NPCR and SEER have provided a rich source of data to CBTRUS that has allowed us to document robust phenomena and explore several potential explanations. However, epidemiological studies are limited by their dependence on population-specific registries.5 In addition, the SEER programs mainly collect information from patient medical records. Thus, variables that are not reliably reported in medical records will not be useful from an analytical perspective.8 Moreover, bias from regional influences, such as diagnostic practices, reporting patterns, and case definition, should be considered.5 Lastly, SEER and NPCR do not provide data on whether the pituitary tumors are hormone releasing or non–hormone releasing. 534
Conclusions
In the present study we give current incidence rates of and time trends for pituitary tumors in the US. Although our methods provide reasonable estimates of the true incidence of pituitary tumors in the era of modern diagnostic tools, the true geographic variations in the epidemiology of pituitary tumors remain uncertain.14 Given the passage of the Benign Brain Tumor Cancer Registries Amendment Act in 2004, it will be several years before comprehensive data on pituitary tumor incidence are available from major cancer registries. In our large patient cohort with pituitary tumors reported between 2004 and 2009, the incidence of pituitary tumors was found to increase. Possible explanations for the increase include changes in documentation, J Neurosurg / Volume 121 / September 2014
Epidemiology of pituitary tumors in the US, 2004–2009 changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population. Future analyses will need to compare our findings with theirs to see if this incidence is still on the rise. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Dr. Selman owns stock in Osteoplastics II and has stock options in Surgical Theater. Dr. Barnholtz-Sloan was funded in part by the Case Comprehensive Cancer Center Support Grant (NCI P30 CA043703). Support for the CBTRUS in 2013 was provided by the National Brain Tumor Society (www.braintumor.org), the Pediatric Brain Tumor Foundation (www.curethekids.org), other private donations, and the CDC under Cooperative Agreement 5U58DP003831-02. The contents in this report are solely the responsibility of the authors and do not necessarily represent the official view of the CDC. Author contributions to the study and manuscript preparation include the following. Conception and design: Barnholtz-Sloan, Gittleman, Ostrom, Kruchko. Acquisition of data: Barnholtz-Sloan, Kruchko. Analysis and interpretation of data: Barnholtz-Sloan, Gittleman. Drafting the article: Barnholtz-Sloan, Gittleman, Ostrom, Farah, Ondracek, Kruchko. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: BarnholtzSloan. Statistical analysis: Gittleman, Ostrom. Administrative/technical/material support: Wolinsky, Kruchko. Study supervision: Barnholtz-Sloan. References 1. Asa SL, Ezzat S: The pathogenesis of pituitary tumours. Nat Rev Cancer 2:836–849, 2002 2. Ciccarelli A, Daly AF, Beckers A: The epidemiology of prolactinomas. Pituitary 8:3–6, 2005 3. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A: High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:4769–4775, 2006 4. Dolecek TA, Propp JM, Stroup NE, Kruchko C: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol 14 (Suppl 5):v1–v49, 2012 (Erratum in Neuro Oncol 15:646–647, 2013) 5. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance
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ML, et al: The prevalence of pituitary adenomas: a systematic review. Cancer 101:613–619, 2004 6. Fernandez A, Karavitaki N, Wass JAH: Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72:377–382, 2010 7. Hemminki K, Försti A, Ji J: Incidence and familial risks in pituitary adenoma and associated tumors. Endocr Relat Cancer 14:103–109, 2007 8. McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA: Demographic differences in incidence for pituitary adenoma. Pituitary 14:23–30, 2011 9. Melmed S: Pathogenesis of pituitary tumors. Nat Rev Endocrinol 7:257–266, 2011 10. Morris Z, Whiteley WN, Longstreth WT Jr, Weber F, Lee YC, Tsushima Y, et al: Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 339:b3016, 2009 11. Nilsson B, Gustavasson-Kadaka E, Bengtsson BA, Jonsson B: Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab 85: 1420–1425, 2000 12. Ónnestam L, Berinder K, Burman P, Dahlqvist P, Engström BE, Wahlberg J, et al: National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab 98:626–635, 2013 13. Popovic V, Damjanovic S, Micic D, Nesovic M, Djurovic M, Petakov M, et al: Increased incidence of neoplasia in patients with pituitary adenomas. Clin Endocrinol (Oxf) 49:441–445, 1998 14. Raappana A, Koivukangas J, Ebeling T, Pirilä T: Incidence of pituitary adenomas in Northern Finland in 1992-2007. J Clin Endocrinol Metab 95:4268–4275, 2010 15. Sivakumar W, Chamoun R, Nguyen V, Couldwell WT: Incidental pituitary adenomas. Neurosurg Focus 31(6):E18, 2011 16. Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, et al: Incidental findings on brain MRI in the general population. N Engl J Med 357:1821–1828, 2007 Manuscript submitted August 27, 2013. Accepted May 8, 2014. Portions of this work were presented in poster form at the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology held in San Francisco, California, on November 23, 2013. Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.5.JNS131819. Address correspondence to: Jill Barnholtz-Sloan, Ph.D., Case Comprehensive Cancer Center, CWRU School of Medicine, 11100 Euclid Ave., Wearn 152, Cleveland, OH 44106-5065. email: jsb42@ case.edu.
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